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Sample records for early postnatal neurogenesis

  1. Conserved properties of dentate gyrus neurogenesis across postnatal development revealed by single-cell RNA sequencing.

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    Hochgerner, Hannah; Zeisel, Amit; Lönnerberg, Peter; Linnarsson, Sten

    2018-02-01

    The dentate gyrus of the hippocampus is a brain region in which neurogenesis persists into adulthood; however, the relationship between developmental and adult dentate gyrus neurogenesis has not been examined in detail. Here we used single-cell RNA sequencing to reveal the molecular dynamics and diversity of dentate gyrus cell types in perinatal, juvenile, and adult mice. We found distinct quiescent and proliferating progenitor cell types, linked by transient intermediate states to neuroblast stages and fully mature granule cells. We observed shifts in the molecular identity of quiescent and proliferating radial glia and granule cells during the postnatal period that were then maintained through adult stages. In contrast, intermediate progenitor cells, neuroblasts, and immature granule cells were nearly indistinguishable at all ages. These findings demonstrate the fundamental similarity of postnatal and adult neurogenesis in the hippocampus and pinpoint the early postnatal transformation of radial glia from embryonic progenitors to adult quiescent stem cells.

  2. Specific radiosensitivy and postnatal neurogenesis of the dentate gyrus of rabbits

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    Gueneau, Gerard.

    1982-09-01

    Adult and young rabbits were delivered a gamma exposure of 4.5 Gy. A light and electron microscope cytological investigation of the hippocampal region in the early hours following the exposure showed the particular radiosensitivity of the dentate gyrus which was demonstrated by: 1) pycnotic cells to be found at the basis of the granular cell layer (subgranular zone) exclusively; 2) a more discrete injury of the granular layer where most nuclei showed a lighter chromatin appearing as ''light spots''. Both radioinduced injuries are described, especially their kinetics, importance, and the effects of dose and age of the animal. The presence of pycnotic cells in the subgranular zone was related to the late postnatal neurogenesis occurring in this zone. The pattern and chronology of this late postnatal neurogenesis was investigated by autoradiography following 3 H thymidine injection. Finally, two series of investigations combining autoradiography and irradiation brought further data on the radiosensitivity and radioresistance of the dental gyrus cells and demonstrated the recovery capacity of the subgranular zone [fr

  3. Neuronal Subtype Generation During Postnatal Olfactory Bulb Neurogenesis.

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    Angelova, Alexandra; Tiveron, Marie-Catherine; Cremer, Harold; Beclin, Christophe

    2018-01-01

    In the perinatal and adult forebrain, regionalized neural stem cells lining the ventricular walls produce different types of olfactory bulb interneurons. Although these postnatal stem cells are lineage related to their embryonic counterparts that produce, for example, cortical, septal, and striatal neurons, their output at the level of neuronal phenotype changes dramatically. Tiveron et al. investigated the molecular determinants underlying stem cell regionalization and the gene expression changes inducing the shift from embryonic to adult neuron production. High-resolution gene expression analyses of different lineages revealed that the zinc finger proteins, Zic1 and Zic2, are postnatally induced in the dorsal olfactory bulb neuron lineage. Functional studies demonstrated that these factors confer a GABAergic and calretinin-positive phenotype to neural stem cells while repressing dopaminergic fate. Based on these findings, we discuss the molecular mechanisms that allow acquisition of new traits during the transition from embryonic to adult neurogenesis. We focus on the involvement of epigenetic marks and emphasize why the identification of master transcription factors, that instruct the fate of postnatally generated neurons, can help in deciphering the mechanisms driving fate transition from embryonic to adult neuron production.

  4. Neuronal Subtype Generation During Postnatal Olfactory Bulb Neurogenesis

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    Alexandra Angelova

    2018-02-01

    Full Text Available In the perinatal and adult forebrain, regionalized neural stem cells lining the ventricular walls produce different types of olfactory bulb interneurons. Although these postnatal stem cells are lineage related to their embryonic counterparts that produce, for example, cortical, septal, and striatal neurons, their output at the level of neuronal phenotype changes dramatically. Tiveron et al. investigated the molecular determinants underlying stem cell regionalization and the gene expression changes inducing the shift from embryonic to adult neuron production. High-resolution gene expression analyses of different lineages revealed that the zinc finger proteins, Zic1 and Zic2, are postnatally induced in the dorsal olfactory bulb neuron lineage. Functional studies demonstrated that these factors confer a GABAergic and calretinin-positive phenotype to neural stem cells while repressing dopaminergic fate. Based on these findings, we discuss the molecular mechanisms that allow acquisition of new traits during the transition from embryonic to adult neurogenesis. We focus on the involvement of epigenetic marks and emphasize why the identification of master transcription factors, that instruct the fate of postnatally generated neurons, can help in deciphering the mechanisms driving fate transition from embryonic to adult neuron production.

  5. Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.

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    Kim, Ju Young; Liu, Cindy Y; Zhang, Fengyu; Duan, Xin; Wen, Zhexing; Song, Juan; Feighery, Emer; Lu, Bai; Rujescu, Dan; St Clair, David; Christian, Kimberly; Callicott, Joseph H; Weinberger, Daniel R; Song, Hongjun; Ming, Guo-li

    2012-03-02

    How extrinsic stimuli and intrinsic factors interact to regulate continuous neurogenesis in the postnatal mammalian brain is unknown. Here we show that regulation of dendritic development of newborn neurons by Disrupted-in-Schizophrenia 1 (DISC1) during adult hippocampal neurogenesis requires neurotransmitter GABA-induced, NKCC1-dependent depolarization through a convergence onto the AKT-mTOR pathway. In contrast, DISC1 fails to modulate early-postnatal hippocampal neurogenesis when conversion of GABA-induced depolarization to hyperpolarization is accelerated. Extending the period of GABA-induced depolarization or maternal deprivation stress restores DISC1-dependent dendritic regulation through mTOR pathway during early-postnatal hippocampal neurogenesis. Furthermore, DISC1 and NKCC1 interact epistatically to affect risk for schizophrenia in two independent case control studies. Our study uncovers an interplay between intrinsic DISC1 and extrinsic GABA signaling, two schizophrenia susceptibility pathways, in controlling neurogenesis and suggests critical roles of developmental tempo and experience in manifesting the impact of susceptibility genes on neuronal development and risk for mental disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Protracted postnatal neurogenesis and radiosensitivity in the rabbit's dentate gyrus

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    Gueneau, G.; Baille, V.; Dubos, M.; Court, L.

    1986-01-01

    In the hippocampal formation of a 3-month-old rabbit submitted to a 4.5 Gy gamma irradiation a cytologic study with light and electron microscopy allowed us to make clear the dentate gyrus particular radiosensitivity as soon as the first hours after irradiation. The pycnosis lesion observed in the subgranular zone has drawn our attention in particular. We apply ourselves to describe and precise the lesion and its evolution; thanks to an autoradiographic study, we have shown its link with late postnatal neurogenesis which goes on in this zone and at last we have used the subgranular cells 'radiosensitivity as a biological test allowing to compare the various rays' effects (gamma and neutron rays). In the brain of a one-month-old monkey submitted to a 4 Gy total irradiation the same pycnotic lesion is observed: 1) in the dentate gyrus's subgranular zone and 2) in the cerebellum's outer granular layer. These two postnatal proliferative zones remain particularly sensitive to ionizing radiations. (orig.)

  7. Age-dependent kinetics of dentate gyrus neurogenesis in the absence of cyclin D2

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    Ansorg Anne

    2012-05-01

    Full Text Available Abstract Background Adult neurogenesis continuously adds new neurons to the dentate gyrus and the olfactory bulb. It involves the proliferation and subsequent differentiation of neuronal progenitors, and is thus closely linked to the cell cycle machinery. Cell cycle progression is governed by the successive expression, activation and degradation of regulatory proteins. Among them, D-type cyclins control the exit from the G1 phase of the cell cycle. Cyclin D2 (cD2 has been shown to be required for the generation of new neurons in the neurogenic niches of the adult brain. It is differentially expressed during hippocampal development, and adult cD2 knock out (cD2KO mice virtually lack neurogenesis in the dentate gyrus and olfactory bulb. In the present study we examined the dynamics of postnatal and adult neurogenesis in the dentate gyrus (DG of cD2KO mice. Animals were injected with bromodeoxyuridine at seven time points during the first 10 months of life and brains were immunohistochemically analyzed for their potential to generate new neurons. Results Compared to their WT litters, cD2KO mice had considerably reduced numbers of newly born granule cells during the postnatal period, with neurogenesis becoming virtually absent around postnatal day 28. This was paralleled by a reduction in granule cell numbers, in the volume of the granule cell layer as well as in apoptotic cell death. CD2KO mice did not show any of the age-related changes in neurogenesis and granule cell numbers that were seen in WT litters. Conclusions The present study suggests that hippocampal neurogenesis becomes increasingly dependent on cD2 during early postnatal development. In cD2KO mice, hippocampal neurogenesis ceases at a time point at which the tertiary germinative matrix stops proliferating, indicating that cD2 becomes an essential requirement for ongoing neurogenesis with the transition from developmental to adult neurogenesis. Our data further support the notion that

  8. Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation

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    Lucassen, P.J.; Oomen, C.A.; Naninck, E.F.G.; Fitzsimons, C.P.; van Dam, A.M.; Czeh, B.; Korosi, A.

    2015-01-01

    Exposure to stress is one of the best-known negative regulators of adult neurogenesis (AN). We discuss changes in neurogenesis in relation to exposure to stress, glucocorticoid hormones, and inflammation, with a particular focus on early development and on lasting effects of stress. Although the

  9. Early Postnatal but Not Late Adult Neurogenesis Is Impaired in the Pitx3-Mutant Animal Model of Parkinson's Disease

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    Moritz D. Brandt

    2017-08-01

    Full Text Available The generation of new neurons in the adult dentate gyrus has functional implications for hippocampal formation. Reduced hippocampal neurogenesis has been described in various animal models of hippocampal dysfunction such as dementia and depression, which are both common non-motor-symptoms of Parkinson's disease (PD. As dopamine plays an important role in regulating precursor cell proliferation, the loss of dopaminergic neurons in the substantia nigra (SN in PD may be related to the reduced neurogenesis observed in the neurogenic regions of the adult brain: subventricular zone (SVZ and dentate gyrus (DG. Here we examined adult hippocampal neurogenesis in the Pitx3-mutant mouse model of PD (aphakia mice, which phenotypically shows a selective embryonic degeneration of dopamine neurons within the SN and to a smaller extent in the ventral tegmental area (VTA. Proliferating cells were labeled with BrdU in aphakia mice and healthy controls from 3 to 42 weeks of age. Three weeks old mutant mice showed an 18% reduction of proliferating cells in the DG and of 26% in the SVZ. Not only proliferation but also the number of new neurons was impaired in young aphakia mice resulting in 33% less newborn cells 4 weeks after BrdU-labeling. Remarkably, however, the decline in the number of proliferating cells in the neurogenic regions vanished in older animals (8–42 weeks indicating that aging masks the effect of dopamine depletion on adult neurogenesis. Region specific reduction in precursor cells proliferation correlated with the extent of dopaminergic degeneration in mesencephalic subregions (VTA and SN, which supports the theory of age- and region-dependent regulatory effects of dopaminergic projections. Physiological stimulation of adult neurogenesis by physical activity (wheel running almost doubled the number of proliferating cells in the dentate gyrus of 8 weeks old aphakia mice to a number comparable to that of wild-type mice, abolishing the slight

  10. Early Postnatal Lipopolysaccharide Exposure Leads to Enhanced Neurogenesis and Impaired Communicative Functions in Rats.

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    Yi Pang

    Full Text Available Perinatal infection is a well-identified risk factor for a number of neurodevelopmental disorders, including brain white matter injury (WMI and Autism Spectrum Disorders (ASD. The underlying mechanisms by which early life inflammatory events cause aberrant neural, cytoarchitectural, and network organization, remain elusive. This study is aimed to investigate how systemic lipopolysaccharide (LPS-induced neuroinflammation affects microglia phenotypes and early neural developmental events in rats. We show here that LPS exposure at early postnatal day 3 leads to a robust microglia activation which is characterized with mixed microglial proinflammatory (M1 and anti-inflammatory (M2 phenotypes. More specifically, we found that microglial M1 markers iNOS and MHC-II were induced at relatively low levels in a regionally restricted manner, whereas M2 markers CD206 and TGFβ were strongly upregulated in a sub-set of activated microglia in multiple white and gray matter structures. This unique microglial response was associated with a marked decrease in naturally occurring apoptosis, but an increase in cell proliferation in the subventricular zone (SVZ and the dentate gyrus (DG of hippocampus. LPS exposure also leads to a significant increase in oligodendrocyte lineage population without causing discernible hypermyelination. Moreover, LPS-exposed rats exhibited significant impairments in communicative and cognitive functions. These findings suggest a possible role of M2-like microglial activation in abnormal neural development that may underlie ASD-like behavioral impairments.

  11. Abrogation of Early Apoptosis Does Not Alter Late Inhibition of Hippocampal Neurogenesis After Irradiation

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    Li Yuqing; Aubert, Isabelle; Wong, C. Shun

    2010-01-01

    Purpose: Irradiation of the adult brain results in acute apoptosis of neural progenitors and vascular endothelial cells, as well as late dysfunction of neural progenitors and inhibition of neurogenesis. We sought to determine whether the early apoptotic response has a causative role in late inhibition of neurogenesis after cranial irradiation. Methods and Materials: Using a genetic approach with p53 and smpd1 transgenic mice and a pharmacologic approach with basic fibroblast growth factor (bFGF) to abrogate the early apoptotic response, we evaluated the late inhibition of neurogenesis in the hippocampal dentate gyrus after cranial irradiation. Results: In dentate gyrus, subgranular neural progenitors underwent p53-dependent apoptosis within 24 h after irradiation. Despite a near abrogation of neural progenitor apoptosis in p53-/- mice, the reduction in newborn neurons in dentate gyrus at 9 weeks after irradiation in p53-/- mice was not different from that observed in wildtype controls. Endothelial cell apoptosis after radiation is mediated by membrane damage initiated by activation of acid sphingomyelinase (ASMase). Deletion of the smpd1 gene (which encodes ASMase) attenuated the apoptotic response of endothelial cells. At 9 weeks after irradiation, the inhibition of hippocampal neurogenesis was not rescued by ASMase deficiency. Intravenous administration of bFGF protected both endothelial cells and neural progenitors against radiation-induced apoptosis. There was no protection against inhibition of neurogenesis at 9 weeks after irradiation in bFGF-treated mice. Conclusion: Early apoptotic death of neural progenitors, endothelial cells, or both does not have a causative association with late inhibition of neurogenesis after irradiation.

  12. Targeted electroporation of defined lateral ventricular walls: a novel and rapid method to study fate specification during postnatal forebrain neurogenesis

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    Cremer Harold

    2011-04-01

    Full Text Available Abstract Background Postnatal olfactory bulb (OB neurogenesis involves the generation of granule and periglomerular cells by neural stem cells (NSCs located in the walls of the lateral ventricle (LV. Recent studies show that NSCs located in different regions of the LV give rise to different types of OB neurons. However, the molecular mechanisms governing neuronal specification remain largely unknown and new methods to approach these questions are needed. Results In this study, we refine electroporation of the postnatal forebrain as a technique to perform precise and accurate delivery of transgenes to NSCs located in distinct walls of the LV in the mouse. Using this method, we confirm and expand previous studies showing that NSCs in distinct walls of the LV produce neurons that invade different layers of the OB. Fate mapping of the progeny of radial glial cells located in these distinct LV walls reveals their specification into defined subtypes of granule and periglomerular neurons. Conclusions Our results provide a baseline with which future studies aiming at investigating the role of factors in postnatal forebrain neuronal specification can be compared. Targeted electroporation of defined LV NSC populations will prove valuable to study the genetic factors involved in forebrain neuronal specification.

  13. Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

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    Sourial, Mary; Doering, Laurie C

    2017-07-01

    The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  14. The mammalian adult neurogenesis gene ontology (MANGO provides a structural framework for published information on genes regulating adult hippocampal neurogenesis.

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    Rupert W Overall

    Full Text Available BACKGROUND: Adult hippocampal neurogenesis is not a single phenotype, but consists of a number of sub-processes, each of which is under complex genetic control. Interpretation of gene expression studies using existing resources often does not lead to results that address the interrelatedness of these processes. Formal structure, such as provided by ontologies, is essential in any field for comprehensive interpretation of existing knowledge but, until now, such a structure has been lacking for adult neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS: We have created a resource with three components 1. A structured ontology describing the key stages in the development of adult hippocampal neural stem cells into functional granule cell neurons. 2. A comprehensive survey of the literature to annotate the results of all published reports on gene function in adult hippocampal neurogenesis (257 manuscripts covering 228 genes to the appropriate terms in our ontology. 3. An easy-to-use searchable interface to the resulting database made freely available online. The manuscript presents an overview of the database highlighting global trends such as the current bias towards research on early proliferative stages, and an example gene set enrichment analysis. A limitation of the resource is the current scope of the literature which, however, is growing by around 100 publications per year. With the ontology and database in place, new findings can be rapidly annotated and regular updates of the database will be made publicly available. CONCLUSIONS/SIGNIFICANCE: The resource we present allows relevant interpretation of gene expression screens in terms of defined stages of postnatal neuronal development. Annotation of genes by hand from the adult neurogenesis literature ensures the data are directly applicable to the system under study. We believe this approach could also serve as an example to other fields in a 'bottom-up' community effort complementing the already

  15. Early detection and treatment of postnatal depression in primary care.

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    Davies, Bronwen R; Howells, Sarah; Jenkins, Meryl

    2003-11-01

    Postnatal depression has a relatively high incidence and gives rise to considerable morbidity. There is sound evidence supporting the use of the Edinburgh Postnatal Depression Scale as a screening tool for possible postnatal depression. This paper reports on a project developed by two health visitors and a community mental health nurse working in the United Kingdom. The aim of the project was to improve the early detection and treatment of postnatal depression in the population of the general practice to which they were attached. The health visitors screened for postnatal depression in the course of routine visits on four occasions during the first postpartum year. Women identified as likely to be suffering from postnatal depression were offered 'listening visits' as a first-line intervention, with referral on to the general practitioner and/or community mental health nurse if indicated. Data collected over 3 years showed that the project succeeded in its aim of enhancing early detection and treatment of postnatal depression. These findings replicate those of other studies. The data also showed that a substantial number of women were identified for the first time as likely to be suffering from postnatal depression at 12 months postpartum. Women screened for the first time at 12 months were at greater risk than those who had been screened earlier than this. Health visitors should screen for postnatal depression throughout the period of their contact with mothers, not solely in the immediate postnatal period. It is particularly important to screen women who, for whatever reason, were not screened when their child was younger. The knowledge and skills needed to use the Edinburgh Postnatal Depression Scale and provide first-line intervention and onward referral can be developed at practitioner level through close collaborative working.

  16. Administration of Zinc plus Cyclo-(His-Pro Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes

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    Bo Young Choi

    2017-01-01

    Full Text Available The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro (ZC on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ-induced diabetes. ZC (27 mg/kg was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase or 45 (late phase days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes.

  17. Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories

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    Jesse Daniel Cushman

    2012-02-01

    Full Text Available Postnatal-neurogenesis (PNN contributes neurons to olfactory bulb (OB and dentate gyrus (DG throughout juvenile development, but the quantitative amount, temporal dynamics and functional roles of this contribution have not been defined. By using transgenic mouse models for cell lineage tracing and conditional cell ablation, we found that juvenile neurogenesis gradually increased the total number of granule neurons by approximately 40% in OB, and by 25% in DG, between two weeks and two months of age, and that total numbers remained stable thereafter. These findings indicate that the overwhelming majority of net postnatal neuronal addition in these regions occurs during the juvenile period and that adult neurogenesis contributes primarily to replacement of granule cells in both regions. Behavioral analysis in our conditional cell ablation mouse model showed that complete loss of PNN throughout both the juvenile and adult period produced a specific set of sex-dependent cognitive changes. We observed normal hippocampus-independent delay fear conditioning, but excessive generalization of fear to a novel auditory stimulus, which is consistent with a role for PNN in psychopathology. Standard contextual fear conditioning was intact, however, pre-exposure dependent contextual fear was impaired suggesting a specific role for PNN in incidental contextual learning. Contextual discrimination between two highly similar contexts was enhanced; suggesting either enhanced contextual pattern separation or impaired temporal integration. We also observed a reduced reliance on olfactory cues, consistent with a role for OB PNN in the efficient processing of olfactory information. Thus, juvenile neurogenesis adds substantively to the total numbers of granule neurons in OB and DG during periods of critical juvenile behavioral development, including weaning, early social interactions and sexual maturation, and plays a sex-dependent role in fear memories.

  18. Differential Postnatal Expression of Neuronal Maturation Markers in the Dentate Gyrus of Mice and Rats

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    Tijana Radic

    2017-11-01

    Full Text Available The dentate gyrus (DG is a unique structure of the hippocampus that is distinguished by ongoing neurogenesis throughout the lifetime of an organism. The development of the DG, which begins during late gestation and continues during the postnatal period, comprises the structural formation of the DG as well as the establishment of the adult neurogenic niche in the subgranular zone (SGZ. We investigated the time course of postnatal maturation of the DG in male C57BL/6J mice and male Sprague-Dawley rats based on the distribution patterns of the immature neuronal marker doublecortin (DCX and a marker for mature neurons, calbindin (CB. Our findings demonstrate that the postnatal DG is marked by a substantial maturation with a high number of DCX-positive granule cells (GCs during the first two postnatal weeks followed by a progression toward more mature patterns and increasing numbers of CB-positive GCs within the subsequent 2 weeks. The most substantial shift in maturation of the GC population took place between P7 and P14 in both mice and rats, when young, immature DCX-positive GCs became confined to the innermost part of the GC layer (GCL, indicative of the formation of the SGZ. These results suggest that the first month of postnatal development represents an important transition phase during which DG neurogenesis and the maturation course of the GC population becomes analogous to the process of adult neurogenesis. Therefore, the postnatal DG could serve as an attractive model for studying a growing and functionally maturing neural network. Direct comparisons between mice and rats revealed that the transition from immature DCX-positive to mature CB-positive GCs occurs more rapidly in the rat by approximately 4–6 days. The remarkable species difference in the speed of maturation on the GC population level may have important implications for developmental and neurogenesis research in different rodent species and strains.

  19. Lower early postnatal oxygen saturation target and risk of ductus arteriosus closure failure.

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    Inomata, Kei; Taniguchi, Shinji; Yonemoto, Hiroki; Inoue, Takeshi; Kawase, Akihiko; Kondo, Yuichi

    2016-11-01

    Early postnatal hyperoxia is a major risk factor for retinopathy of prematurity (ROP) in extremely premature infants. To reduce the occurrence of ROP, we adopted a lower early postnatal oxygen saturation (SpO 2 ) target range (85-92%) from April 2011. Lower SpO 2 target range, however, may lead to hypoxemia and an increase in the risk of ductus arteriosus (DA) closure failure. The aim of this study was therefore to determine whether a lower SpO 2 target range, during the early postnatal stage, increases the risk of DA closure failure. Infants born at closure failure in period 2 (21%) was significantly higher than that in period 1 (1%). On multivariate logistic regression analysis, the lower oxygen saturation target range was an independent risk factor for DA closure failure. Lower early postnatal oxygen saturation target range increases the risk of DA closure failure. © 2016 Japan Pediatric Society.

  20. PREVENTION OF NIPPLE CRACKS OF THE MAMMARY GLAND IN THE EARLY POSTNATAL PERIOD

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    Marina L. Travina

    2017-01-01

    Full Text Available Preservation and prolongation of the lactation period is not only a guarantee of the child's full physical and mental development but also one of the most important methods for reducing the risk of developing breast cancer. Problems with the mammary gland nipple in a woman in the early postnatal period lead to a refusal of lactation. We carried out a retrospective analysis (period from 2010 to 2016 of the causes of traumatizing mammary gland nipples in the early postnatal period in 172 women (mean age 29.1 ± 4.3 years. Methods of prevention and treatment of nipple injuries in the early postnatal period have been offered for the lactation period prolongation.

  1. Early life stress- and sex-dependent effects on hippocampal neurogenesis

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    Lucassen, P.J.; Korosi, A.; Krugers, H.J.; Oomen, C.A.; Fink, G.

    2017-01-01

    Neurogenesis refers to the birth of new neurons in an adult brain, a form of structural plasticity that has been implicated in cognition, mood, and anxiety, and is well regulated by environmental and hormonal factors. Exposure to stress (hormones) generally inhibits neurogenesis. Here, we discuss

  2. Enriched dairy fat matrix diet prevents early life lipopolysaccharide-induced spatial memory impairment at adulthood.

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    Dinel, A L; Rey, C; Baudry, C; Fressange-Mazda, C; Le Ruyet, P; Nadjar, A; Pallet, P; Joffre, C; Layé, S

    2016-10-01

    Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

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    Eric J. Neuberger

    2017-09-01

    Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

  4. Neurogenesis dan Faktor-Faktor yang Berpengaruh

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    Ria Puspitawati

    2015-09-01

    Full Text Available Development of nerve tissue is known as neurogenesis. Vertebrate neve system has various functional capabilities from sensory perception, motor coordination, to the ability in producing motivation, spatial abilities, learning and memorizing due to various cell types that accurately connected and interact to each other. The connections between various nerve cells are continuously developed from the embryonic time until the early period of life. Recent studies have showed that neurogenesis in certain regions of nerve tissue can still be found in adults. This article reviews the cellular mechanism of neurogenesis and conditions that have role in the process.

  5. Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid

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    Berry Juliandi

    2015-12-01

    Full Text Available Prenatal exposure to valproic acid (VPA, an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running.

  6. NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain

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    Murray Kerren

    2011-02-01

    Full Text Available Abstract From an early postnatal period and throughout life there is a continuous production of olfactory bulb (OB interneurons originating from neuronal precursors in the subventricular zone. To reach the OB circuits, immature neuroblasts migrate along the rostral migratory stream (RMS. In the present study, we employed cultured postnatal mouse forebrain slices and used lentiviral vectors to label neuronal precursors with GFP and to manipulate the expression levels of the Na-K-2Cl cotransporter NKCC1. We investigated the role of this Cl- transporter in different stages of postnatal neurogenesis, including neuroblast migration and integration in the OB networks once they have reached the granule cell layer (GCL. We report that NKCC1 activity is necessary for maintaining normal migratory speed. Both pharmacological and genetic manipulations revealed that NKCC1 maintains high [Cl-]i and regulates the resting membrane potential of migratory neuroblasts whilst its functional expression is strongly reduced at the time cells reach the GCL. As in other developing systems, NKCC1 shapes GABAA-dependent signaling in the RMS neuroblasts. Also, we show that NKCC1 controls the migration of neuroblasts in the RMS. The present study indeed indicates that the latter effect results from a novel action of NKCC1 on the resting membrane potential, which is independent of GABAA-dependent signaling. All in all, our findings show that early stages of the postnatal recruitment of OB interneurons rely on precise, orchestrated mechanisms that depend on multiple actions of NKCC1.

  7. Postnatal early overnutrition causes long-term renal decline in aging male rats.

    Science.gov (United States)

    Yim, Hyung Eun; Yoo, Kee Hwan; Bae, In Sun; Hong, Young Sook; Lee, Joo Won

    2014-02-01

    We evaluated the influence of postnatal early overnutrition on renal pathophysiological changes in aging rats. Three or 10 male pups per mother were assigned to either the small litter (SL) or normal litter (control) groups, respectively, during the first 21 d of life. The effects of early postnatal overnutrition were determined at 12 mo. SL rats weighed more than controls between 4 d and 6 mo of age (P renal cortex were higher in SL rats (P aging SL rats (P aging kidney and can lead to systolic hypertension with reduced intrarenal renin activity.

  8. Prenatal and early postnatal stress and later life inflammation

    DEFF Research Database (Denmark)

    Pedersen, Jolene Masters; Mortensen, Erik Lykke; Christensen, Dinne Skjærlund

    2018-01-01

    BACKGROUND: Evidence suggests that maternal psychological and social stress during the prenatal period and in childhood represent an important condition that may adversely impact the anatomy and physiology of the developing child with implications for a number of health-related conditions...... and postnatal stressor data was collected at year one follow-up. A series of ordinary least square regression models were performed with the stress measures as the exposures and C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor necrosis factor α (TNF-α) separately as the outcomes...... in the first year of life, was associated with higher levels of CRP and IL-6. The accumulation of social stressors in the early postnatal period was associated with higher levels of CRP and IL-6 but not IL-10 and TNF-α. The accumulation of stressors in the prenatal and postnatal periods combined was associated...

  9. Third harmonic generation imaging of intact human cerebral organoids to assess key components of early neurogenesis in Rett Syndrome (Conference Presentation)

    Science.gov (United States)

    Yildirim, Murat; Feldman, Danielle; Wang, Tianyu; Ouzounov, Dimitre G.; Chou, Stephanie; Swaney, Justin; Chung, Kwanghun; Xu, Chris; So, Peter T. C.; Sur, Mriganka

    2017-02-01

    Rett Syndrome (RTT) is a pervasive, X-linked neurodevelopmental disorder that predominantly affects girls. It is mostly caused by a sporadic mutation in the gene encoding methyl CpG-binding protein 2 (MeCP2).The clinical features of RTT are most commonly reported to emerge between the ages of 6-18 months and implicating RTT as a disorder of postnatal development. However, a variety of recent evidence from our lab and others demonstrates that RTT phenotypes are present at the earliest stages of brain development including neurogenesis, migration, and patterning in addition to stages of synaptic and circuit development and plasticity. We have used RTT patient-derived induced pluripotent stem cells to generate 3D human cerebral organoids that can serve as a model for human neurogenesis in vitro. We aim to expand on our existing findings in order to determine aberrancies at individual stages of neurogenesis by performing structural and immunocytochemical staining in isogenic control and MeCP2-deficient organoids. In addition, we aim to use Third Harmonic Generation (THG) microscopy as a label-free, nondestructive 3D tissue visualization method in order to gain a complete understanding of the structural complexity that underlies human neurogenesis. As a proof of concept, we have performed THG imaging in healthy intact human cerebral organoids cleared with SWITCH. We acquired an intrinsic THG signal with the following laser configurations: 400 kHz repetition rate, 65 fs pulse width laser at 1350 nm wavelength. In these THG images, nuclei are clearly delineated and cross sections demonstrate the depth penetration capacity (< 1mm) that extends throughout the organoid. Imaging control and MeCP2-deficient human cerebral organoids in 2D sections reveals structural and protein expression-based alterations that we expect will be clearly elucidated via both THG and three-photon fluorescence microscopy.

  10. Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm.

    Science.gov (United States)

    Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

    2017-07-01

    BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

  11. Low-Dose Sevoflurane Promotes Hippocampal Neurogenesis and Facilitates the Development of Dentate Gyrus-Dependent Learning in Neonatal Rats

    Directory of Open Access Journals (Sweden)

    Chong Chen

    2015-04-01

    Full Text Available Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8% sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4–6 were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.

  12. Efficient in vivo electroporation of the postnatal rodent forebrain.

    Directory of Open Access Journals (Sweden)

    Camille Boutin

    Full Text Available Functional gene analysis in vivo represents still a major challenge in biomedical research. Here we present a new method for the efficient introduction of nucleic acids into the postnatal mouse forebrain. We show that intraventricular injection of DNA followed by electroporation induces strong expression of transgenes in radial glia, neuronal precursors and neurons of the olfactory system. We present two proof-of-principle experiments to validate our approach. First, we show that expression of a human isoform of the neural cell adhesion molecule (hNCAM-140 in radial glia cells induces their differentiation into cells showing a neural precursor phenotype. Second, we demonstrate that p21 acts as a cell cycle inhibitor for postnatal neural stem cells. This approach will represent an important tool for future studies of postnatal neurogenesis and of neural development in general.

  13. Effects of amphetamine administration on neurogenesis in adult rats

    Directory of Open Access Journals (Sweden)

    Tomasz Stępień

    2017-12-01

    Full Text Available In our study expression of phospho-(Ser-10-histone H3 (pH3S10, a marker for the early stage of neurogenesis, and cellular early response genes were investigated using c-Fos protein as an example of a transcription factor in the neurogenic process in rats. Neurogenesis in the adult brain is regulated by endo- and exogenous factors, which influence the proliferation potential of progenitor cells and accelerate the dendritic development of newborn neurons. D-amphetamine, a psychoactive substance, is one of the exogenous factors able to influence the process of neurogenesis. The rats were injected with D-amphetamine at a dose of 1.5 mg/kg/body weight (b.w. under one administration scheme. Analysis of the pH3S10 and c-Fos expression levels in the group of D-amphetamine administered rats provided evidence of enhanced expression of these proteins in the regions of neurogenesis occurrence in rats. However, conclusions concerning stimulant effects of amphetamine on neurogenesis should be formulated with great caution, taking into account amphetamine dosage and the administration scheme. It should also be remembered that doses of psychoactive substances used in animal models can be lethal to humans.

  14. Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells.

    Science.gov (United States)

    Farioli-Vecchioli, Stefano; Mattera, Andrea; Micheli, Laura; Ceccarelli, Manuela; Leonardi, Luca; Saraulli, Daniele; Costanzi, Marco; Cestari, Vincenzo; Rouault, Jean-Pierre; Tirone, Felice

    2014-07-01

    Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated the beneficial effects of physical exercise in paradigms of impaired neurogenesis. Here, we demonstrate that running fully reverses the deficient adult neurogenesis within the hippocampus and subventricular zone of the lateral ventricle, observed in mice lacking the antiproliferative gene Btg1. We also evaluated for the first time how running influences the cell cycle kinetics of stem and precursor subpopulations of wild-type and Btg1-null mice, using a new method to determine the cell cycle length. Our data show that in wild-type mice running leads to a cell cycle shortening only of NeuroD1-positive progenitor cells. In contrast, in Btg1-null mice, physical exercise fully reactivates the defective hippocampal neurogenesis, by shortening the S-phase length and the overall cell cycle duration of both neural stem (glial fibrillary acidic protein(+) and Sox2(+)) and progenitor (NeuroD1(+)) cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in Btg1-null early-postnatal mice and to expand the pool of adult neural stem and progenitor cells. Such a sustained increase of cell proliferation in Btg1-null mice after running provides a long-lasting increment of proliferation, differentiation, and production of newborn neurons, which rescues the impaired pattern separation previously identified in Btg1-null mice. This study shows that running positively affects the cell cycle kinetics of specific subpopulations of newly generated neurons and suggests that the plasticity of neural stem cells without cell cycle inhibitory control is reactivated by running, with implications for the long-term modulation of neurogenesis. © 2014 AlphaMed Press.

  15. Implication of neuro-genesis during brain development in behavior disorders caused by depleted uranium

    International Nuclear Information System (INIS)

    Legrand, Marie

    2016-01-01

    Humans are continuously exposed to neurotoxic compounds in the environment. The developing brain is more susceptible to neurotoxic compounds and modifications in its growth could lead to disorders in adulthood. Uranium (U) is an environmental heavy metal and induces behavioral disorders as well as affects neurochemistry. The aim of my thesis was to investigate whether depleted uranium (DU) exposure affects neuro-genesis processes, which are implicated in brain development and in synaptic plasticity in adults. While DU increased cell proliferation in the hippocampal neuro-epithelium and decreased cell death at prenatal stages, DU lead to opposite effects in the dentate gyrus at postnatal stages. Moreover, DU had an inhibitory effect on the transition toward neuronal differentiation pathway during development. At adult stage, DU induced a decrease in neuronal differentiation but has no impact in cell proliferation. Finally, DU exposure during brain development caused depressive like behavior at late postnatal and adult stage, and decreased spatial memory at adult stage. Consequently, DU exposure during brain development caused modification in neuro-genesis processes associated to cognitive and emotional disorders at adult age. U could present a threat to human health, especially in pregnant women and children. (author)

  16. Risk of childhood overweight after exposure to tobacco smoking in prenatal and early postnatal life

    DEFF Research Database (Denmark)

    Møller, Susanne Eifer; Ajslev, Teresa Adeltoft; Andersen, Camilla Schou

    2014-01-01

    OBJECTIVE: To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account. METHODS: From the Danish National Birth Cohort a total of 32,747 families were identified with avai......OBJECTIVE: To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account. METHODS: From the Danish National Birth Cohort a total of 32,747 families were identified...... with available information on maternal smoking status in child's pre- and postnatal life and child's birth weight, and weight and height at age 7 years. Outcome was overweight according to the International Obesity Task Force gender and age specific body mass index. Smoking exposure was categorized into four...... groups: no exposure (n = 25,076); exposure only during pregnancy (n = 3,343); exposure only postnatally (n = 140); and exposure during pregnancy and postnatally (n = 4,188). Risk of overweight according to smoking status as well as dose-response relationships were estimated by crude and adjusted odds...

  17. Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats.

    Science.gov (United States)

    Chen, Chong; Shen, Feng-Yan; Zhao, Xuan; Zhou, Tao; Xu, Dao-Jie; Wang, Zhi-Ru; Wang, Ying-Wei

    2015-01-01

    Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks. © The Author(s) 2015.

  18. Paracrine control of vascularization and neurogenesis by neurotrophins.

    Science.gov (United States)

    Emanueli, Costanza; Schratzberger, Peter; Kirchmair, Rudolf; Madeddu, Paolo

    2003-10-01

    The neuronal system plays a fundamental role in the maturation of primitive embryonic vascular network by providing a paracrine template for blood vessel branching and arterial differentiation. Furthermore, postnatal vascular and neural regeneration cooperate in the healing of damaged tissue. Neurogenesis continues in adulthood although confined to specific brain regions. Following ischaemic insult, neural staminal cells contribute towards the healing process through the stimulation of neurogenesis and vasculogenesis. Evidence indicates that nerves and blood vessels exert a reciprocal control of their own growth by paracrine mechanisms. For instance, guidance factors, including vascular endothelial growth factor A (VEGF-A) and semaphorins, which share the ability of binding neuropilin receptors, play a pivotal role in the tridimensional growth pattern of arterial vessels and nerves. Animal models and clinical studies have demonstrated a role of VEGF-A in the pathogenesis of ischaemic and diabetic neuropathies. Further, supplementation with VEGF-A ameliorates neuronal recovery by exerting protective effects on nerves and stimulating reparative neovascularization. Human tissue kallikrein, a recently discovered angiogenic and arteriogenic factor, accelerates neuronal recovery by stimulating the growth of vasa nervorum. Conversely, the neurotrophin nerve growth factor, known to regulate neuronal survival and differentiation, is now regarded as a stimulator of angiogenesis and arteriogenesis. These results indicate that angiogenesis and neurogenesis are paracrinally regulated by growth factors released by endothelial cells and neurons. Supplementation of these growth factors, alone or in combination, could benefit the treatment of ischaemic diseases and neuropathies.

  19. Repeatability of Maternal Report on Prenatal, Perinatal and Early Postnatal Factors

    DEFF Research Database (Denmark)

    Hermann, Diana; Suling, Marc; Reisch, Lucia

    2011-01-01

    To investigate the repeatability of maternal self-reported prenatal, perinatal and early postnatal factors within the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study. Design: Data are from the baseline survey of the longitudin...

  20. Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome.

    Science.gov (United States)

    Corrales, Andrea; Parisotto, Eduardo B; Vidal, Verónica; García-Cerro, Susana; Lantigua, Sara; Diego, Marian; Wilhem Filho, Danilo; Sanchez-Barceló, Emilio J; Martínez-Cué, Carmen; Rueda, Noemí

    2017-09-15

    Melatonin administered during adulthood induces beneficial effects on cognition and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we investigated the effects of pre- and post-natal melatonin treatment on behavioral and cognitive abnormalities and on several neuromorphological alterations (hypocellularity, neurogenesis impairment and increased oxidative stress) that appear during the early developmental stages in TS mice. Pregnant TS females were orally treated with melatonin or vehicle from the time of conception until the weaning of the offspring, and the pups continued to receive the treatment from weaning until the age of 5 months. Melatonin administered during the pre- and post-natal periods did not improve the cognitive impairment of TS mice as measured by the Morris Water maze or fear conditioning tests. Histological alterations, such as decreased proliferation (Ki67+ cells) and hippocampal hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented by melatonin. However, melatonin partially regulated brain oxidative stress by modulating the activity of the primary antioxidant enzymes (superoxide dismutase in the cortex and catalase in the cortex and hippocampus) and slightly decreasing the levels of lipid peroxidation in the hippocampus of TS mice. These results show the inability of melatonin to prevent cognitive impairment in TS mice when it is administered at pre- and post-natal stages. Additionally, our findings suggest that to induce pro-cognitive effects in TS mice during the early stages of development, in addition to attenuating oxidative stress, therapies should aim to improve other altered processes, such as hippocampal neurogenesis and/or hypocellularity. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Tooth loss early in life suppresses neurogenesis and synaptophysin expression in the hippocampus and impairs learning in mice.

    Science.gov (United States)

    Kubo, Kin-Ya; Murabayashi, Chika; Kotachi, Mika; Suzuki, Ayumi; Mori, Daisuke; Sato, Yuichi; Onozuka, Minoru; Azuma, Kagaku; Iinuma, Mitsuo

    2017-02-01

    Tooth loss induced neurological alterations through activation of a stress hormone, corticosterone. Age-related hippocampal morphological and functional changes were accelerated by early tooth loss in senescence-accelerated mouse prone 8 (SAMP8). In order to explore the mechanism underlying the impaired hippocampal function resulting from early masticatory dysfunction due to tooth loss, we investigated the effects of early tooth loss on plasma corticosterone levels, learning ability, neurogenesis, and synaptophysin expression in the hippocampus later in life of SAMP8 mice. We examined the effects of tooth loss soon after tooth eruption (1 month of age) on plasma corticosterone levels, learning ability in the Morris water maze, newborn cell proliferation, survival and differentiation in the hippocampal dentate gyrus, and synaptophysin expression in the hippocampus of aged (8 months of age) SAMP8 mice. Aged mice with early tooth loss exhibited increased plasma corticosterone levels, hippocampus-dependent learning deficits in the Morris water maze, decreased cell proliferation, and cell survival in the dentate gyrus, and suppressed synaptophysin expression in the hippocampus. Newborn cell differentiation in the hippocampal dentate gyrus, however, was not affected by early tooth loss. These findings suggest that learning deficits in aged SAMP8 mice with tooth loss soon after tooth eruption are associated with suppressed neurogenesis and decreased synaptophysin expression resulting from increased plasma corticosterone levels, and that long-term tooth loss leads to impaired cognitive function in older age. Copyright © 2016. Published by Elsevier Ltd.

  2. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications.

    Science.gov (United States)

    Galea, L A M; Wainwright, S R; Roes, M M; Duarte-Guterman, P; Chow, C; Hamson, D K

    2013-11-01

    The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress. © 2013 British Society for Neuroendocrinology.

  3. Overexpression of Mineralocorticoid Receptors in the Mouse Forebrain Partly Alleviates the Effects of Chronic Early Life Stress on Spatial Memory, Neurogenesis and Synaptic Function in the Dentate Gyrus

    Directory of Open Access Journals (Sweden)

    Sofia Kanatsou

    2017-05-01

    Full Text Available Evidence from human studies suggests that high expression of brain mineralocorticoid receptors (MR may promote resilience against negative consequences of stress exposure, including childhood trauma. We examined, in mice, whether brain MR overexpression can alleviate the effects of chronic early life stress (ELS on contextual memory formation under low and high stress conditions, and neurogenesis and synaptic function of dentate gyrus granular cells. Male mice were exposed to ELS by housing the dam with limited nesting and bedding material from postnatal day (PND 2 to 9. We investigated the moderating role of MRs by using forebrain-specific transgenic MR overexpression (MR-tg mice. Low-stress contextual (i.e., object relocation memory formation was hampered by ELS in wildtype but not MR-tg mice. Anxiety like behavior and high-stress contextual (i.e., fear memory formation were unaffected by ELS and/or MR expression level. At the cellular level, an interaction effect was observed between ELS and MR overexpression on the number of doublecortin-positive cells, with a significant difference between the wildtype ELS and MR-tg ELS groups. No interaction was found regarding Ki-67 and BrdU staining. A significant interaction between ELS and MR expression was further observed with regard to mEPSCs and mIPSC frequency. The ratio of evoked EPSC/IPSC or NMDA/AMPA responses was unaffected. Overall, these results suggest that ELS affects contextual memory formation under low stress conditions as well as neurogenesis and synaptic transmission in dentate granule cells, an effect that can be alleviated by MR-overexpression.

  4. Histone deacetylases control neurogenesis in embryonic brain by inhibition of BMP2/4 signaling.

    Directory of Open Access Journals (Sweden)

    Maya Shakèd

    Full Text Available BACKGROUND: Histone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain. PRINCIPAL FINDINGS: As a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited. CONCLUSIONS: Our results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical

  5. EFFECTS OF EARLY POSTNATAL ANOXIA ON ADULT LEARNING AND EMOTION IN RATS

    NARCIS (Netherlands)

    BUWALDA, B; NYAKAS, C; VOSSELMAN, HJ; LUITEN, PGM; Vosselman, Henk Jan

    Cognitive functioning, behavioural attention and anxiety were studied in adult male Wistar rats after early postnatal anoxia. Spatial memory performance in the holeboard learning task was impaired in anoxic rats when compared with control animals. Attention assessed by the behavioural immobility

  6. Designing, developing, and testing an app for parents being discharged early postnatally

    DEFF Research Database (Denmark)

    Danbjørg, Dorthe Boe; Wagner, Lis; Clemensen, Jane

    2014-01-01

    In Denmark and internationally, earlier discharge of postnatal patients presents a challenge to find innovative ways of providing follow-up support to new mothers who may be discharged early. The purpose of this participatory design study is to describe the process of the design, development, and...... testing. •We designed, developed, and testet an app for the iPad.•The app was viable, but the app requires refinements and wider testing.•The app met the new families' needs for follow-up support.•There is a potential for ensuring postnatal security with the use of technology....

  7. Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

    Science.gov (United States)

    Molina-Jiménez, Tania; Limón-Morales, Ofelia; Bonilla-Jaime, Herlinda

    2018-03-01

    Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Prenatal and early postnatal depression and child maltreatment among Japanese fathers.

    Science.gov (United States)

    Takehara, Kenji; Suto, Maiko; Kakee, Naoko; Tachibana, Yoshiyuki; Mori, Rintaro

    2017-08-01

    We investigated the association of paternal depression in the prenatal and early postnatal period with child maltreatment tendency at two months postpartum among Japanese fathers. This population-based longitudinal study recruited Japanese perinatal women and their partners living in Nishio City, Aichi, Japan. Of the 270 fathers who participated, 196 were included in the analysis. All data were collected via self-administrated questionnaires at four time points: 20 weeks' gestation and in the first few days, one month, and two months postpartum. Paternal depression was assessed using the Edinburgh Postnatal Depression Scale. Three definitions of paternal depression were coded based on participants' scores on this measure: prenatal, prior, and current. Child maltreatment tendency was evaluated using the Child Maltreatment Scale at two months postpartum. The associations of the three definitions of paternal depression and child maltreatment tendency were separately analyzed using logistic regression analysis. The prevalence of prenatal, prior, and current paternal depression was 9.7%, 10.2%, and 8.8%, respectively. According to the multivariate analysis, current paternal depression was significantly associated with child maltreatment tendency at two months postpartum (adjusted odds ratio: 7.77, 95% CI: 1.83-33.02). The other two types of depression, however, were not related to child maltreatment tendency. Thus, current paternal depression increased the risk of child maltreatment tendency in the postnatal period, suggesting that early detection and treatment of paternal depression might be useful for the prevention of child maltreatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Enhancing early postnatal care: findings from a major reform of maternity care in three Australian hospitals.

    Science.gov (United States)

    Yelland, Jane; Krastev, Ann; Brown, Stephanie

    2009-08-01

    four hospitals comprising a health network in Melbourne, Australia, implemented a range of initiatives aimed at enhancing women's experiences of postnatal maternity care. to compare women's views and experiences of early postnatal care before and after implementation of maternity enhancement initiatives. 'before and after' study design incorporating two postal surveys of recent mothers (baseline and post-implementation). four hospitals in Melbourne, Australia. Analysis of postnatal outcomes was confined to three hospitals where the initiatives were fully operational. 1256 women participated in the baseline survey in 1999 (before implementing the initiative) and 1050 women responded to the post-implementation survey in 2001. the response to the 1999 baseline survey was 65.3% (1256/1922) and to the 2001 post-implementation survey 57.4% (1050/1829). Comparative analysis revealed a statistically significant improvement in overall ratings of hospital postnatal care; the level of advice and support received in relation to discharge and going home; the sensitivity of caregivers; and the proportion of women receiving domiciliary care after discharge. There was little change in the time women spent in hospital after birth between the two survey time-points. Over 90% of women reported one or more health problems in the first 3 months postpartum. The proportion of women reporting physical or emotional health problems between the two surveys did not change. mainstream maternity care can be restructured to improve women's experiences of early postnatal care. maternity service providers should consider a multi-faceted approach to reorienting postnatal services and improving women's experiences of care. Approaches worthy of consideration include attempts to ensure consistency and continuity of care through staffing arrangements, guidelines and protocols; an emphasis on planning for postnatal care during pregnancy; the use of evidence to inform both consumer information and advice

  10. Absence of the calcium-binding protein calretinin, not of calbindin D-28k, causes a permanent impairment of murine adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Kiran eTodkar

    2012-04-01

    Full Text Available Calretinin (CR and calbindin D-28k (CB are cytosolic EF-hand Ca2+-binding proteins and function as Ca2+ buffers affecting the spatiotemporal aspects of Ca2+ transients and possibly also as Ca2+ sensors modulating signaling cascades. In the adult hippocampal circuitry, CR and CB are expressed in specific principal neurons and subsets of interneurons. In addition, CR is transiently expressed within the neurogenic dentate gyrus (DG niche. CR and CB expression during adult neurogenesis mark critical transition stages, onset of differentiation for CR and the switch to adult-like connectivity for CB. Absence of either protein during these stages in null-mutant mice may have functional consequences and contribute to some aspects of the identified phenotypes. We report the impact of CR- and CB-deficiency on the proliferation and differentiation of progenitor cells within the subgranular zone (SGZ neurogenic niche of the DG. Effects were evaluated I 2 and 4 weeks postnatally, during the transition period of the proliferative matrix to the adult state, and II in adult animals (3 months to trace possible permanent changes in adult neurogenesis. The absence of CB from differentiated DG granule cells has no retrograde effect on the proliferative activity of progenitor cells, nor affects survival or migration/differentiation of newborn neurons in the adult DG including the SGZ. On the contrary, lack of CR from immature early postmitotic granule cells causes an early loss in proliferative capacity of the SGZ that is maintained into adult age, when it has a further impact on the migration/survival of newborn granule cells. The transient CR expression at the onset of adult neurogenesis differentiation may thus have two functions: I to serve as a self-maintenance signal for the pool of cells at the same stage of neurogenesis contributing to their survival/differentiation, and II it may contribute to retrograde signaling required for maintenance of the progenitor

  11. Consequences of early postnatal benzodiazepines exposure in rats. II. Social behavior

    Directory of Open Access Journals (Sweden)

    Anna eMikulecka

    2014-05-01

    Full Text Available Social behavior represents an integral part of behavioral repertoire of rats particularly sensitive to pharmacological and environmental influences. The aim of the present study was to investigate whether early postnatal clonazepam (CZP exposure can induce age-dependent changes related to expression of social behavior. The drug was administered from postnatal day (P 7 until P11 at daily doses of 0.1, 0.5 and 1.0 mg/kg i.p. We designed three experiments to assess whether exposure to CZP affects social behavior in respect to the age of rats and the test circumstances, specifically their familiarity with test conditions during adolescence (P32, social behavior in juveniles and adolescents (P18-P42 and social behavior in a resident-intruder paradigm. The frequency and duration of a various patterns of social behavior related to play and social investigation not related to play were evaluated. The results showed that CZP postnatal exposure decreased social play behavior regardless of age and familiarity or unfamiliarity of experimental environment but did not affect the social investigation per se. When rats were confronted with an intruder in their home cages intense wrestling and inhibition of genital investigation were found. In conclusion, these findings show that short-term CZP postnatal exposure inhibits social play behavior and alters specific patterns of social behavior in an age and environment related manner

  12. Evaluation of a neurodevelopmental model of schizophrenia--early postnatal PCP treatment in attentional set-shifting

    DEFF Research Database (Denmark)

    Broberg, Brian Villumsen; Dias, Rebecca; Glenthøj, Birte Yding

    2008-01-01

    Phencyclidine (PCP) was administered to male and female Lister hooded rats on postnatal days (PND) 7, 9 and 11. All PCP animals tested in adulthood (PND 53-93) showed deficits in cognitive flexibility, specifically in their ability to shift attentional set, compared to controls. This novel finding...... is reminiscent of the impairment observed in schizophrenia patients, and supports the validity of the early postnatal PCP regimen as a disease-like model....

  13. Transcriptomic Analysis Of Purified Embryonic Neural Stem Cells From Zebrafish Embryos Reveals Signalling Pathways Involved In Glycine-dependent Neurogenesis

    Directory of Open Access Journals (Sweden)

    Eric eSAMARUT

    2016-03-01

    Full Text Available How is the initial set of neurons correctly established during the development of the vertebrate central nervous system? In the embryo, glycine and GABA are depolarizing due the immature chloride gradient, which is only reversed to become hyperpolarizing later in post-natal development. We previously showed that glycine regulates neurogenesis via paracrine signalling that promotes calcium transients in neural stem cells (NSCs and their differentiation into interneurons within the spinal cord of the zebrafish embryo. However, the subjacent molecular mechanisms are not yet understood. Our previous work suggests that early neuronal progenitors were not differentiating correctly in the developing spinal cord. As a result, we aimed at identifying the downstream molecular mechanisms involved specifically in NSCs during glycine-dependent embryonic neurogenesis. Using a gfap:GFP transgenic line, we successfully purified NSCs by fluorescence-activated cell sorting (FACS from whole zebrafish embryos and in embryos in which the glycine receptor was knocked down. The strength of this approach is that it focused on the NSC population while tackling the biological issue in an in vivo context in whole zebrafish embryos. After sequencing the transcriptome by RNA-sequencing, we analyzed the genes whose expression was changed upon disruption of glycine signalling and we confirmed the differential expression by independent RTqPCR assay. While over a thousand genes showed altered expression levels, through pathway analysis we identified 14 top candidate genes belonging to five different canonical signalling pathways (signalling by calcium, TGF-beta, sonic hedgehog, Wnt and p53-related apoptosis that are likely to mediate the promotion of neurogenesis by glycine.

  14. Prenatal and early postnatal supplementation with long-chain polyunsaturated fatty acids : neurodevelopmental considerations

    NARCIS (Netherlands)

    Hadders-Algra, Mijna

    2011-01-01

    It takes >20 y before the human brain obtains its complex adult configuration. Most dramatic neurodevelopmental changes occur prenatally and early postnatally, including a major transformation in cortical organization 3-4 mo after term. The long-lasting changes have practical implications for

  15. Neurogenic function in rats with unilateral hippocampal sclerosis that experienced early-life status epilepticus

    Science.gov (United States)

    Dunleavy, Mark; Schindler, Clara K; Shinoda, Sachiko; Crilly, Shane; Henshall, David C

    2014-01-01

    Status epilepticus in the adult brain invariably causes an increase in hippocampal neurogenesis and the appearance of ectopic cells and this has been implicated as a causal factor in epileptogenesis. The effect of status epilepticus on neurogenesis in the developing brain is less well characterized and models of early-life seizures typically do not reproduce the hippocampal damage common to human mesial temporal sclerosis. We recently reported that evoking status epilepticus by intra-amygdala microinjection of kainic acid in post-natal (P) day 10 rats caused substantial acute neuronal death within the ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis and spontaneous recurrent seizures. Here, we examined the expression of a selection of genes associated with neurogenesis and assessed neurogenic function in this model. Protein levels of several markers of neurogenesis including polysialic acid neural cell adhesion molecule, neuroD and doublecortin were reduced in the hippocampus three days after status epilepticus in P10 rats. In contrast, protein levels of neurogenesis markers were similar to control in rats at P55. Pulse-chase experiments using thymidine analogues suggested there was a reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas numbers of new neurons labelled in epileptic rats at P55 with hippocampal sclerosis were similar to controls. The present study suggests that status epilepticus in the immature brain suppresses neurogenesis but the neurogenic potential is retained in animals that later develop hippocampal sclerosis. PMID:25755841

  16. Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

    Science.gov (United States)

    Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

    2016-04-13

    Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner.

  17. Food restriction reduces neurogenesis in the avian hippocampal formation.

    Directory of Open Access Journals (Sweden)

    Barbara-Anne Robertson

    Full Text Available The mammalian hippocampus is particularly vulnerable to chronic stress. Adult neurogenesis in the dentate gyrus is suppressed by chronic stress and by administration of glucocorticoid hormones. Post-natal and adult neurogenesis are present in the avian hippocampal formation as well, but much less is known about its sensitivity to chronic stressors. In this study, we investigate this question in a commercial bird model: the broiler breeder chicken. Commercial broiler breeders are food restricted during development to manipulate their growth curve and to avoid negative health outcomes, including obesity and poor reproductive performance. Beyond knowing that these chickens are healthier than fully-fed birds and that they have a high motivation to eat, little is known about how food restriction impacts the animals' physiology. Chickens were kept on a commercial food-restricted diet during the first 12 weeks of life, or released from this restriction by feeding them ad libitum from weeks 7-12 of life. To test the hypothesis that chronic food restriction decreases the production of new neurons (neurogenesis in the hippocampal formation, the cell proliferation marker bromodeoxyuridine was injected one week prior to tissue collection. Corticosterone levels in blood plasma were elevated during food restriction, even though molecular markers of hypothalamic-pituitary-adrenal axis activation did not differ between the treatments. The density of new hippocampal neurons was significantly reduced in the food-restricted condition, as compared to chickens fed ad libitum, similar to findings in rats at a similar developmental stage. Food restriction did not affect hippocampal volume or the total number of neurons. These findings indicate that in birds, like in mammals, reduction in hippocampal neurogenesis is associated with chronically elevated corticosterone levels, and therefore potentially with chronic stress in general. This finding is consistent with the

  18. The effect of early postnatal discharge from hospital for women and infants: a systematic review protocol.

    Science.gov (United States)

    Jones, Eleanor; Taylor, Beck; MacArthur, Christine; Pritchett, Ruth; Cummins, Carole

    2016-02-08

    The length of postnatal hospital stay has declined over the last 40 years. There is little evidence to support a policy of early discharge following birth, and there is some concern about whether early discharge of mothers and babies is safe. The Cochrane review on the effects of early discharge from hospital only included randomised controlled trials (RCTs) which are problematic in this area, and a systematic review including other study designs is required. The aim of this broader systematic review is to determine possible effects of a policy of early postnatal discharge on important maternal and infant health-related outcomes. A systematic search of published literature will be conducted for randomised controlled trials, non-randomised controlled trials (NRCTs), controlled before-after studies (CBA), and interrupted time series studies (ITS) that report on the effect of a policy of early postnatal discharge from hospital. Databases including Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and Science Citation Index will be searched for relevant material. Reference lists of articles will also be searched in addition to searches to identify grey literature. Screening of identified articles and data extraction will be conducted in duplicate and independently. Methodological quality of the included studies will be assessed using the Effective Practice and Organisation of Care (EPOC) criteria for risk of bias tool. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analysis using a random effects model will be used to combine data. Where significant heterogeneity is present, data will be combined in a narrative synthesis. The findings will be reported according to the preferred reporting items for systematic reviews (PRISMA) statement. Information on the effects of early postnatal discharge from hospital will be important for policy makers and clinicians providing maternity care. This review will also identify any gaps in the current

  19. Evaluation of a neurodevelopmental model of schizophrenia - Early postnatal PCP treatment in attentional set-shifting

    DEFF Research Database (Denmark)

    Broberg, B.V.; Dias, R.; Olsen, C.K.

    2008-01-01

    Phencyclidine (PCP) was administered to male and female Lister hooded rats on postnatal days (PND) 7, 9 and 11. All PCP animals tested in adulthood (PND 53-93) showed deficits in cognitive flexibility, specifically in their ability to shift attentional set, compared to controls. This novel finding...... is reminiscent of the impairment observed in schizophrenia patients, and supports the validity of the early postnatal PCP regimen as a disease-like model. (c) 2008 Elsevier B.V. All rights reserved Udgivelsesdato: 2008...

  20. Neurogenesis and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disease, characterized in the brain by amyloid plaque deposits and neurofibrillary tangles. It is the most common form of dementia among older people. There is at present no cure for AD, and current treatments consist mainly in drug therapy. Potential therapies for AD involve gene and cellular therapy. The recent confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS provide new opportunities for cellular therapy in the CNS, particularly for AD, and to better understand brain physiopathology. Hence, researchers have aimed at characterizing neurogenesis in patients with AD. Studies show that neurogenesis is increased in these patients, and in animal models of AD. The effect of drugs used to treat AD on neurogenesis is currently being investigated, to identify whether neurogenesis contributes to their therapeutic activities.

  1. Neurogenesis and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disease, characterized in the brain by amyloid plaque deposits and neurofibrillary tangles. It is the most common form of dementia among older people. There is at present no cure for AD, and current treatments consist mainly in drug therapy. Potential therapies for AD involve gene and cellular therapy. The recent confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS provide new opportunities for cellular therapy in the CNS, particularly for AD, and to better understand brain physiopathology. Hence, researchers have aimed at characterizing neurogenesis in patients with AD. Studies show that neurogenesis is increased in these patients, and in animal models of AD. The effect of drugs used to treat AD on neurogenesis is currently being investigated, to identify whether neurogenesis contributes to their therapeutic activities.

  2. Early postnatal docosahexaenoic acid levels and improved preterm brain development

    OpenAIRE

    Tam, Emily W.Y.; Chau, Vann; Barkovich, A. James; Ferriero, Donna M.; Miller, Steven P.; Rogers, Elizabeth E.; Grunau, Ruth E.; Synnes, Anne R.; Xu, Duan; Foong, Justin; Brant, Rollin; Innis, Sheila M.

    2016-01-01

    Background Preterm birth has a dramatic impact on polyunsaturated fatty acid exposures for the developing brain. This study examined the association between postnatal fatty acid levels and measures of brain injury and development, as well as outcomes. Methods A cohort of 60 preterm newborns (24?32 weeks GA) was assessed using early and near-term MRI studies. Red blood cell fatty acid composition was analyzed coordinated with each scan. Outcome at a mean of 33 months corrected age was assessed...

  3. Intervention among new parents followed up by an interview study exploring their experiences of telemedicine after early postnatal discharge.

    Science.gov (United States)

    Danbjørg, D B; Wagner, L; Kristensen, B R; Clemensen, J

    2015-06-01

    a move towards earlier postnatal discharge raises the challenge of finding new ways to support families when they are discharged early after childbirth. to explore how postnatal parents experienced the use of telemedicine following early discharge from hospital (i.e. 24 hours after childbirth) by investigating if they consider that their postnatal needs are met, and whether or not they experience a sense of security and parental self-efficacy. intervention followed by a qualitative interview study. The intervention took place on a postnatal ward with approximately 1000 births a year. An app including chat, a knowledgebase and automated messages was trialled between postnatal parents at home and the hospital. Parents had access to the app for seven days after discharge. 42 new mothers were recruited from the postnatal ward in accordance with the inclusion criteria (i.e. discharged within 24 hours of childbirth). Both parents were invited for interview. 42 sets of parents participated in the trial, and 28 sets agreed to be interviewed. Interviews (n=28) were conducted with 27 mothers and 11 fathers. Parents were interviewed together in 10 cases, 17 mothers were interviewed alone, and one father was interviewed alone. The data analysis was inspired by systematic text condensation based on Giorgi׳s descriptive phenomenological method. parents were confident in use of the app, and did not experience any barriers in contacting the nurses via asynchronous communication. Parents received timely information and guidance by communicating online, and felt that their follow-up support needs were met. parents viewed the app as a lifeline, and saw it as a means of informing and guiding them following early discharge from hospital after childbirth. As such, this app shows potential for enhancing self-efficacy and postnatal sense of security. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Birth Weight, Postnatal Weight Gain, and Childhood Adiposity in Relation to Lipid Profile and Blood Pressure During Early Adolescence.

    Science.gov (United States)

    Hulst, Andraea Van; Barnett, Tracie A; Paradis, Gilles; Roy-Gagnon, Marie-Hélène; Gomez-Lopez, Lilianne; Henderson, Mélanie

    2017-08-04

    Different pathways likely underlie the association between early weight gain and cardiovascular disease risk. We examined whether birth weight for length relationship and weight gain up to 2 years of age are associated with lipid profiles and blood pressure (BP) in early adolescence and determined whether childhood adiposity mediates these associations. Data from QUALITY (Quebec Adipose and Lifestyle Investigation in Youth), a cohort of white children with parental history of obesity, were analyzed (n=395). Sex-specific weight for length z scores from birth to 2 years were computed. Rate of postnatal weight gain was estimated using individual slopes of weight for length z -score measurements. Percentage of body fat was measured at 8 to 10 years. Fasting lipids and BP were measured at 10 to 12 years. Using path analysis, we found indirect effects of postnatal weight gain, through childhood adiposity, on all outcomes: Rate of postnatal weight for length gain was positively associated with childhood adiposity, which in turn was associated with unfavorable lipid and BP levels in early adolescence. In contrast, small beneficial direct effects on diastolic BP z scores, independent of weight at other time points, were found for birth weight for length (β=-0.05, 95% CI, -0.09 to -0.002) and for postnatal weight gain (β=-0.02, 95% CI, -0.03 to -0.002). Among children with at least 1 obese parent, faster postnatal weight gain leads to cardiovascular risk factors in early adolescence through its effect on childhood adiposity. Although heavier newborns may have lower BP in early adolescence, this protective direct effect could be offset by a deleterious indirect effect linking birth weight to later adiposity. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  5. Prenatal and Early Postnatal Diagnosis of Congenital Toxoplasmosis in a Setting With No Systematic Screening in Pregnancy

    Science.gov (United States)

    Stajner, Tijana; Bobic, Branko; Klun, Ivana; Nikolic, Aleksandra; Srbljanovic, Jelena; Uzelac, Aleksandra; Rajnpreht, Irena; Djurkovic-Djakovic, Olgica

    2016-01-01

    Abstract To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy. In the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment. PMID:26945416

  6. Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats

    Science.gov (United States)

    Beaudin, Stephane A.; Strupp, Barbara J.; Strawderman, Myla; Smith, Donald R.

    2016-01-01

    Background: Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. Objectives: To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Methods: Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1–21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Results: Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. Conclusions: This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230–237; http://dx.doi.org/10.1289/EHP258 PMID:27384154

  7. Early Postnatal Manganese Exposure Causes Lasting Impairment of Selective and Focused Attention and Arousal Regulation in Adult Rats.

    Science.gov (United States)

    Beaudin, Stephane A; Strupp, Barbara J; Strawderman, Myla; Smith, Donald R

    2017-02-01

    Studies in children and adolescents have associated early developmental manganese (Mn) exposure with inattention, impulsivity, hyperactivity, and oppositional behaviors, but causal inferences are precluded by the correlational nature of the data and generally limited control for potential confounders. To determine whether early postnatal oral Mn exposure causes lasting attentional and impulse control deficits in adulthood, and whether continued lifelong Mn exposure exacerbates these effects, using a rat model of environmental Mn exposure. Neonates were exposed orally to 0, 25 or 50 mg Mn/kg/day during early postnatal life (PND 1-21) or throughout life from PND 1 until the end of the study. In adulthood, the animals were tested on a series of learning and attention tasks using the five-choice serial reaction time task. Early postnatal Mn exposure caused lasting attentional dysfunction due to impairments in attentional preparedness, selective attention, and arousal regulation, whereas associative ability (learning) and impulse control were spared. The presence and severity of these deficits varied with the dose and duration of Mn exposure. This study is the first to show that developmental Mn exposure can cause lasting impairments in focused and selective attention and arousal regulation, and to identify the specific nature of the impairments. Given the importance of attention and arousal regulation in cognitive functioning, these findings substantiate concerns about the adverse effects of developmental Mn exposure in humans. Citation: Beaudin SA, Strupp BJ, Strawderman M, Smith DR. 2017. Early postnatal manganese exposure causes lasting impairment of selective and focused attention and arousal regulation in adult rats. Environ Health Perspect 125:230-237; http://dx.doi.org/10.1289/EHP258.

  8. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    International Nuclear Information System (INIS)

    Zhu, Changlian; Gao, Jianfeng; Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu; Kuhn, Hans-Georg; Blomgren, Klas

    2011-01-01

    Research highlights: → The effect of MRI on the developing brain is a matter of debate. → Repeated exposure to MRI did not affect neurogenesis. → Memory function was not affected by repeated MRI during development. → Neither late gestation nor young postnatal brains were affected by MRI. → Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 o C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  9. Development of the adult neurogenic niche in the hippocampus of mice

    Directory of Open Access Journals (Sweden)

    Zeina eNicola

    2015-05-01

    Full Text Available When does adult hippocampal neurogenesis begin? We describe the development of the neurogenic niche in the subgranular zone (SGZ of the hippocampal dentate gyrus. We did so from the perspective of the situation in the adult.Ontogeny of the dentate gyrus is complex and results in an ectopic neurogenic niche that lifelong generates new granule cells. Neurogenesis during the fetal and early postnatal periods builds the dentate gyrus and gives way to activity-dependent adult neurogenesis. We used markers most relevant to adult neurogenesis research to describe this transition: Nestin, Sox2, BLBP, GFAP, Tbr2, Doublecortin (DCX, NeuroD1 and Prox1. We found that massive changes and a local condensation of proliferating precursor cells occurs between postnatal day 7 (P7, near the peak in proliferation, and P14. Before and around P7, the spatial distribution of cells and the co-localization of markers were distinct from the situation in the adult. Unlike the adult SGZ, the marker pair Nestin/Sox2 and the radial glial marker BLBP were not overlapping during embryonic development, presumably indicating different types of radial glia-like cells. Before P7 GFAP-positive cells in the hilus lacked the radial orientation that is characteristic of the adult type-1 cells. DCX, which is concentrated in type-2b and type-3 progenitor cells and early postmitotic neurons in the adult, showed diffuse expression before P7. Intermediate progenitor cell marker Tbr2 became restricted to the SGZ but was found in the granule cell layer and hilus before. Lineage markers NeuroD1 and Prox1 confirmed this pattern.We conclude that the neurogenic niche of adult neurogenesis is in place well before true adulthood. This might indicate that consistent with the hypothesized function of adult neurogenesis in activity-dependent plasticity, the early transition from postnatal neurogenesis to adult neurogenesis coincides with the time, when the young mice start to become active themselves.

  10. Neurogenesis-mediated forgetting minimizes proactive interference.

    Science.gov (United States)

    Epp, Jonathan R; Silva Mera, Rudy; Köhler, Stefan; Josselyn, Sheena A; Frankland, Paul W

    2016-02-26

    Established memories may interfere with the encoding of new memories, particularly when existing and new memories overlap in content. By manipulating levels of hippocampal neurogenesis, here we show that neurogenesis regulates this form of proactive interference. Increasing hippocampal neurogenesis weakens existing memories and, in doing so, facilitates the encoding of new, conflicting (but not non-conflicting) information in mice. Conversely, decreasing neurogenesis stabilizes existing memories, and impedes the encoding of new, conflicting information. These results suggest that reduced proactive interference is an adaptive benefit of neurogenesis-induced forgetting.

  11. Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition.

    Science.gov (United States)

    Biddinger, Jessica E; Fox, Edward A

    2010-08-04

    Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

    Science.gov (United States)

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

    2014-09-01

    A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. [Formation of antioxidant defence system of geese in embryogenesis and early postnatal ontogenesis].

    Science.gov (United States)

    Danchenko, O O; Kalytka, V V

    2002-01-01

    The features of antioxidant protection of tissues of a liver and blood of the gooses in embriogenesis and early postnatal ontogenesis are found out. Maximal contents TBA active products both in a liver, and in a blood are observed in 28 diurnal embriones. Is shown, that in a liver the activity of basic antioxidant enzymes (superoxide dismutases, catalase and glutathione peroxidase) in a liver is developed already at early stages embriogenesis and is considerably enlarged in the end embriogenesis. The becoming of enzymatic system of a blood descends much more slower.

  14. Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.

    Science.gov (United States)

    Halliday, H L; Ehrenkranz, R A; Doyle, L W

    2003-01-01

    Corticosteroids have been used late in the neonatal period to treat chronic lung disease (CLD) in preterm babies, and early to try to prevent it. CLD is likely to be the result of persisting inflammation in the lung and the use of powerful anti-inflammatory drugs like dexamethasone has some rationale. Early use tends to be associated with increased adverse effects so that studies of moderately early treatment (7-14 days postnatal) might have the dual benefits of fewer side effects and onset of action before chronic inflammation is established. To determine if moderately early (7-14 days) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the prevention and/or treatment of early chronic lung disease in the preterm infant. Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, Cochrane Database of Controlled Trials, MEDLINE (1966 - October 2002), hand searching paediatric and perinatal journals, examining previous review articles and information received from practicing neonatologists. Authors of all studies were contacted, where possible, to confirm details of reported follow-up studies, or to obtain any information about long-term follow-up where none had been reported. Randomised controlled trials of postnatal corticosteroid treatment from 7-14 days of birth in high risk preterm infants were selected for this review. Data regarding clinical outcomes including mortality, CLD (including late rescue with corticosteroids, or need for home oxygen therapy), death or CLD, failure to extubate, complications during the primary hospitalisation (including infection, hyperglycaemia, hypertension, hypertrophic cardiomyopathy, pneumothorax, severe intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), gastrointestinal bleeding, and severe retinopathy of prematurity (ROP)), and long term outcome (including blindness, deafness, cerebral palsy and major neurosensory

  15. Cell Proliferation, Migration, and Neurogenesis in the Adult Brain of the Pulse Type Weakly Electric Fish, Gymnotus omarorum

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    Valentina Olivera-Pasilio

    2017-08-01

    Full Text Available Adult neurogenesis, an essential mechanism of brain plasticity, enables brain development along postnatal life, constant addition of new neurons, neuronal turnover, and/or regeneration. It is amply distributed but negatively modulated during development and along evolution. Widespread cell proliferation, high neurogenic, and regenerative capacities are considered characteristics of teleost brains during adulthood. These anamniotes are promising models to depict factors that modulate cell proliferation, migration, and neurogenesis, and might be intervened to promote brain plasticity in mammals. Nevertheless, the migration path of derived cells to their final destination was not studied in various teleosts, including most weakly electric fish. In this group adult brain morphology is attributed to sensory specialization, involving the concerted evolution of peripheral electroreceptors and electric organs, encompassed by the evolution of neural networks involved in electrosensory information processing. In wave type gymnotids adult brain morphology is proposed to result from lifelong region specific cell proliferation and neurogenesis. Consistently, pulse type weakly electric gymnotids and mormyrids show widespread distribution of proliferation zones that persists in adulthood, but their neurogenic potential is still unknown. Here we studied the migration process and differentiation of newborn cells into the neuronal phenotype in the pulse type gymnotid Gymnotus omarorum. Pulse labeling of S-phase cells with 5-Chloro-2′-deoxyuridine thymidine followed by 1 to 180 day survivals evidenced long distance migration of newborn cells from the rostralmost telencephalic ventricle to the olfactory bulb, and between layers of all cerebellar divisions. Shorter migration appeared in the tectum opticum and torus semicircularis. In many brain regions, derived cells expressed early neuronal markers doublecortin (chase: 1–30 days and HuC/HuD (chase: 7–180 days

  16. Developmental exposure of aflatoxin B1 reversibly affects hippocampal neurogenesis targeting late-stage neural progenitor cells through suppression of cholinergic signaling in rats

    International Nuclear Information System (INIS)

    Tanaka, Takeshi; Mizukami, Sayaka; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Sugita-Konishi, Yoshiko; Yoshida, Toshinori; Shibutani, Makoto

    2015-01-01

    Highlights: • Maternal AFB 1 exposure effect on hippocampal neurogenesis was examined in rats. • AFB 1 reversibly reduced cell proliferation and type-3 progenitor cells in the SGZ. • Suppressed cholinergic signals to GABAergic interneurons may reduce type-3 cells. • Suppressed BDNF–TRKB signaling may contribute to aberration of neurogenesis. • The NOAEL for offspring was determined to be 0.1 ppm (7.1–13.6 μg/kg BW/day). - Abstract: To elucidate the maternal exposure effects of aflatoxin B 1 (AFB 1 ) and its metabolite aflatoxin M 1 , which is transferred into milk, on postnatal hippocampal neurogenesis, pregnant Sprague-Dawley rats were provided a diet containing AFB 1 at 0, 0.1, 0.3, or 1.0 ppm from gestational day 6 to day 21 after delivery on weaning. Offspring were maintained through postnatal day (PND) 77 without AFB 1 exposure. Following exposure to 1.0 ppm AFB 1 , offspring showed no apparent systemic toxicity at weaning, whereas dams showed increased liver weight and DNA repair gene upregulation in the liver. In the hippocampal dentate gyrus of male PND 21 offspring, the number of doublecortin + progenitor cells were decreased, which was associated with decreased proliferative cell population in the subgranular zone at ≥0.3 ppm, although T-box brain 2 + cells, tubulin beta III + cells, gamma-H2A histone family, member X + cells, and cyclin-dependent kinase inhibitor 1A + cells did not fluctuate in number. AFB 1 exposure examined at 1.0 ppm also resulted in transcript downregulation of the cholinergic receptor subunit Chrna7 and dopaminergic receptor Drd2 in the dentate gyrus, although there was no change in transcript levels of DNA repair genes. In the hippocampal dentate hilus, interneurons expressing CHRNA7 or phosphorylated tropomyosin receptor kinase B (TRKB) decreased at ≥0.3 ppm. On PND 77, there were no changes in neurogenesis-related parameters. These results suggested that maternal AFB 1 exposure reversibly affects hippocampal

  17. Developmental Patterns of Doublecortin Expression and White Matter Neuron Density in the Postnatal Primate Prefrontal Cortex and Schizophrenia

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    Fung, Samantha J.; Joshi, Dipesh; Allen, Katherine M.; Sivagnanasundaram, Sinthuja; Rothmond, Debora A.; Saunders, Richard; Noble, Pamela L.; Webster, Maree J.; Shannon Weickert, Cynthia

    2011-01-01

    Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC). Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX), a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque) and density of white matter neurons (humans) during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched controls (n = 37) and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in schizophrenia. PMID

  18. Developmental patterns of doublecortin expression and white matter neuron density in the postnatal primate prefrontal cortex and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Samantha J Fung

    Full Text Available Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC. Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX, a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque and density of white matter neurons (humans during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37 and matched controls (n = 37 and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in

  19. Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

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    Eleni Paizanis

    2007-01-01

    Full Text Available There is a growing body of evidence that neural stem cells reside in the adult central nervous system where neurogenesis occurs throughout lifespan. Neurogenesis concerns mainly two areas in the brain: the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone, where it is controlled by several trophic factors and neuroactive molecules. Neurogenesis is involved in processes such as learning and memory and accumulating evidence implicates hippocampal neurogenesis in the physiopathology of depression. We herein review experimental and clinical data demonstrating that stress and antidepressant treatments affect neurogenesis in opposite direction in rodents. In particular, the stimulation of hippocampal neurogenesis by all types of antidepressant drugs supports the view that neuroplastic phenomena are involved in the physiopathology of depression and underlie—at least partly—antidepressant therapy.

  20. Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance.

    Science.gov (United States)

    Gonzalez-Bulnes, Antonio; Astiz, Susana; Ovilo, Cristina; Lopez-Bote, Clemente J; Sanchez-Sanchez, Raul; Perez-Solana, Maria L; Torres-Rovira, Laura; Ayuso, Miriam; Gonzalez, Jorge

    2014-10-01

    Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity. © 2014 Society for Endocrinology.

  1. Neurogenesis and The Effect of Antidepressants

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    Philippe Taupin

    2006-01-01

    Full Text Available The recent evidence that neurogenesis occurs throughout adulthood and neural stem cells (NSCs reside in the adult central nervous system (CNS suggests that the CNS has the potential for self-repair. Beside this potential, the function of newly generated neuronal cells in the adult brain remains the focus of intense research. The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests that adult neurogenesis may contribute to the biology of depression. The observations that antidepressants, like fluoxetine, increase neurogenesis in the dentate gyrus (DG and neurogenesis is required for the behavioral effect of antidepressants, lead to a new theory for depression and the design of new strategies and drugs for the treatment of depression. However, the role of adult neurogenesis in the etiology of depression remains the source of controversies and debates.

  2. Neurogenesis and the Effect of Antidepressants

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available The recent evidence that neurogenesis occurs throughout adulthood and neural stem cells (NSCs reside in the adult central nervous system (CNS suggests that the CNS has the potential for self-repair. Beside this potential, the function of newly generated neuronal cells in the adult brain remains the focus of intense research. The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests that adult neurogenesis may contribute to the biology of depression. The observations that antidepressants, like fluoxetine, increase neurogenesis in the dentate gyrus (DG and neurogenesis is required for the behavioral effect of antidepressants, lead to a new theory for depression and the design of new strategies and drugs for the treatment of depression. However, the role of adult neurogenesis in the etiology of depression remains the source of controversies and debates.

  3. Do families after early postnatal discharge need new ways to communicate with the hospital? A feasibilility study.

    Science.gov (United States)

    Danbjørg, Dorthe Boe; Wagner, Lis; Clemensen, Jane

    2014-06-01

    the length of the postnatal hospital stay in Denmark as well as globally has been radically reduced over the past 10-20 years and this raises the challenge of finding new ways of providing observation and support to families discharged early, that they otherwise would be provided as inpatients. this study is to identify the nursing support needs of new parents and their infants during the first seven days post partum, by drawing on the experiences of all stakeholders' in early postnatal discharge from hospital, and thereby gaining new knowledge to investigate further whether telemedicine is a viable option in providing the required support. this article describes the first phase of a participatory design process. A qualitative approach guided the research process and the data analysis. Data were collected from participant observation, qualitative interviews with the new parents, focus groups interviews and a workshop attended by the new parents and health-care professionals. the total number of participants in this study was 37; nineteen parents and 18 health-care professionals from one hospital and three municipalities in Denmark. the investigation findings highlighted, amongst other aspects, the importance of individualised postnatal follow-up in which families have increased access to the health-care professionals and are provided with timely information tailored to their specific needs. the present study underscored that the families experiencing early discharge were not provided with seamless individualised follow-up support. They requested more availability from the health-care system to respond to their concerns and questions during the postnatal period. They experienced a barrier in attempting to contact health-care professionals following hospital discharge and they asked for new ways to communicate that would eliminate that barrier and meet their needs for more individualised and timely information and guidance. Copyright © 2013 Elsevier Ltd. All rights

  4. Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

    Science.gov (United States)

    Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

    2015-01-01

    Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Glucagon-Like Peptide-1 as Predictor of Body Mass Index and Dentate Gyrus Neurogenesis: Neuroplasticity and the Metabolic Milieu

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    Jeremy D. Coplan

    2014-01-01

    Full Text Available Glucagon-like peptide-1 (GLP-1 regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1, and body mass index (BMI in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profiles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing effects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues.

  6. The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning.

    Science.gov (United States)

    Li, Ki Angel; Lund, Emilie Torp; Voigt, Jörg-Peter W

    2016-01-01

    The early postnatal period is a sensitive period in rodents as behavioural systems are developing and maturing during this time. However, relatively little information is available about the impact of environmental enrichment on offspring behaviour if enrichment is implemented only during this period. Here, environmental enrichment was provided from postnatal day 1 until weaning. On post-natal day 9, maternal behaviour and nonmaternal behaviour of the dam was observed. Nursing time in the enriched group was reduced but dams showed more non-maternal appetitive behaviours. Offspring were exposed to either the open field or the elevated plus maze (EPM) after weaning. In the open field, rats from the enriched group approached the more aversive inner zone of the open field later than control rats. Offspring from the enriched group made fewer entries into the inner zone and spent less time in this part of the arena. Enrichment had no impact on behaviour in the EPM. The present study provides evidence that postnatal enrichment can interfere with maternal behaviour in rats and can possibly lead to increased anxiety in the offspring. The findings suggest that enrichment procedures can have potentially unintended effects, interfering with the development of emotional behaviours in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Inhibition of Neurogenesis by Zika virus Infection.

    Science.gov (United States)

    Ahmad, Fahim; Siddiqui, Amna; Kamal, Mohammad A; Sohrab, Sayed S

    2018-02-01

    The association between Zika virus infection and neurological disorder has raised urgent global alarm. The ongoing epidemic has triggered quick responses in the scientific community. The first case of Zika virus was reported in 2015 from Brazil and now has spread over 30 countries. Nearly four hundred cases of travel-associated Zika virus infection have also been reported in the United States. Zika virus is primarily transmitted by mosquito belongs to the genus Aedes that are widely distributed throughout the world including the Southern United States. Additionally, the virus can also be transmitted from males to females by sexual contact. The epidemiological investigations during the current outbreak found a causal link between infection in pregnant women and development of microcephaly in their unborn babies. This finding is a cause for grave concern since microcephaly is a serious neural developmental disorder that can lead to significant post-natal developmental abnormalities and disabilities. Recently, published data indicate that Zika virus infection affects the growth of fetal neural progenitor cells and cerebral neurons that results in malformation of cerebral cortex leading to microcephaly. Recently, it has been reported that Zika virus infection deregulates the signaling pathway of neuronal cell and inhibit the neurogenesis resulting into dementia. In this review we have discussed about the information about cellular and molecular mechanisms in neurodegeneration of human neuronal cells and inhibit the neurogenesis. Additionally, this information will be very helpful further not only in neuro-scientific research but also designing and development of management strategies for microcephaly and other mosquito borne disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Role of adult hippocampal neurogenesis in stress resilience

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    Brunno R. Levone

    2015-01-01

    Full Text Available There is a growing appreciation that adult hippocampal neurogenesis plays a role in emotional and cognitive processes related to psychiatric disorders. Although many studies have investigated the effects of stress on adult hippocampal neurogenesis, most have not focused on whether stress-induced changes in neurogenesis occur specifically in animals that are more resilient or more susceptible to the behavioural and neuroendocrine effects of stress. Thus, in the present review we explore whether there is a clear relationship between stress-induced changes in adult hippocampal neurogenesis, stress resilience and antidepressant-induced recovery from stress-induced changes in behaviour. Exposure to different stressors is known to reduce adult hippocampal neurogenesis, but some stressors have also been shown to exert opposite effects. Ablation of neurogenesis does not lead to a depressive phenotype, but it can enhance responsiveness to stress and affect stress susceptibility. Monoaminergic-targeted antidepressants, environmental enrichment and adrenalectomy are beneficial for reversing stress-induced changes in behaviour and have been shown to do so in a neurogenesis-dependant manner. In addition, stress and antidepressants can affect hippocampal neurogenesis, preferentially in the ventral hippocampus. Together, these data show that adult hippocampal neurogenesis may play a role in the neuroendocrine and behavioural responses to stress, although it is not yet fully clear under which circumstances neurogenesis promotes resilience or susceptibility to stress. It will be important that future studies carefully examine how adult hippocampal neurogenesis can contribute to stress resilience/susceptibility so that it may be appropriately exploited for the development of new and more effective treatments for stress-related psychiatric disorders.

  9. Learning-dependent neurogenesis in the olfactory bulb determines long-term olfactory memory.

    Science.gov (United States)

    Sultan, S; Mandairon, N; Kermen, F; Garcia, S; Sacquet, J; Didier, A

    2010-07-01

    Inhibitory interneurons of the olfactory bulb are subjected to permanent adult neurogenesis. Their number is modulated by learning, suggesting that they could play a role in plastic changes of the bulbar network associated with olfactory memory. Adult male C57BL/6 mice were trained in an associative olfactory task, and we analyzed long-term retention of the task 5, 30, and 90 d post-training. In parallel, we assessed the fate of these newborn cells, mapped their distribution in the olfactory bulb and measured their functional implication using the immediate early gene Zif268. In a second set of experiments, we pharmacologically modulated glutamatergic transmission and using the same behavioral task assessed the consequences on memory retention and neurogenesis. Finally, by local infusion of an antimitotic drug, we selectively blocked neurogenesis during acquisition of the task and looked at the effects on memory retention. First we demonstrated that retrieval of an associative olfactory task recruits the newborn neurons in odor-specific areas of the olfactory bulb selected to survive during acquisition of the task and that it does this in a manner that depends on the strength of learning. We then demonstrated that acquisition is not dependent on neurogenesis if long-term retention of the task is abolished by blocking neurogenesis. Adult-born neurons are thus involved in changes in the neural representation of an odor; this underlies long-term olfactory memory as the strength of learning is linked to the duration of this memory. Neurogenesis thus plays a crucial role in long-term olfactory memory.

  10. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

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    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

    2015-08-07

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.

  11. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    International Nuclear Information System (INIS)

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki

    2015-01-01

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture

  12. Taurine increases hippocampal neurogenesis in aging mice

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    Elias Gebara

    2015-05-01

    Full Text Available Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.

  13. Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in Preterm Newborns (STEP-ROP).

    Science.gov (United States)

    Ricard, Caroline A; Dammann, Christiane E L; Dammann, Olaf

    2017-01-01

    Retinopathy of prematurity (ROP) is a disorder of the preterm newborn characterized by neurovascular disruption in the immature retina that may cause visual impairment and blindness. To develop a clinical screening tool for early postnatal prediction of ROP in preterm newborns based on risk information available within the first 48 h of postnatal life. Using data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we created logistic regression models based on infants born <28 completed weeks gestational age. We developed a model with 60% of the data and identified birth weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity, and multiple gestation as predictors of ROP. We tested the model in the remaining 40%, performed tenfold cross-validation, and tested the score in ELGAN study data. Of the 1,052 newborns in the VON database, 627 recorded an ROP status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had severe ROP (stages 3-5). We created a weighted score to predict any ROP based on the multivariable regression model. A cutoff score of 5 had the best sensitivity (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%, 95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI 69-75), but PPV was higher (80%, 95% CI 77-83). STEP-ROP is a promising screening tool. It is easy to calculate, does not rely on extensive postnatal data collection, and can be calculated early after birth. Early ROP screening may help physicians limit patient exposure to additional risk factors, and may be useful for risk stratification in clinical trials aimed at reducing ROP. © 2017 S. Karger AG, Basel.

  14. Adult Neurogenesis and Mental Illness

    Science.gov (United States)

    Schoenfeld, Timothy J; Cameron, Heather A

    2015-01-01

    Several lines of evidence suggest that adult neurogenesis, the production of new neurons in adulthood, may play a role in psychiatric disorders, including depression, anxiety, and schizophrenia. Medications and other treatments for mental disorders often promote the proliferation of new neurons; the time course for maturation and integration of new neurons in circuitry parallels the delayed efficacy of psychiatric therapies; adverse and beneficial experiences similarly affect development of mental illness and neurogenesis; and ablation of new neurons in adulthood alters the behavioral impact of drugs in animal models. At present, the links between adult neurogenesis and depression seem stronger than those suggesting a relationship between new neurons and anxiety or schizophrenia. Yet, even in the case of depression there is currently no direct evidence for a causative role. This article reviews the data relating adult neurogenesis to mental illness and discusses where research needs to head in the future. PMID:25178407

  15. The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants.

    Science.gov (United States)

    Porcelli, Peter J; Weaver, R Grey

    2010-06-01

    Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development. Evaluate relationship between early postnatal nutriture and ROP surgery. Nutrition data was collected for inborn AGA infants, BW 700-1000 g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999). BW and gestational age were 867+/-85 g and 26.3+/-1.2 weeks (n=77, mean+/-1SD). ROP surgery infants(n=11) received more parenteral nutrition, 1648 mL, and less human milk, 13.8 mL/kg-day, and vitamin E, 1.4 mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio=0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations. Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

    Science.gov (United States)

    Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

    2015-03-01

    The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development. Copyright © 2015. Published by Elsevier Inc.

  17. Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice.

    Science.gov (United States)

    Nakanishi, S T; Whelan, P J

    2010-05-01

    During early postnatal development, between birth and postnatal days 8-11, mice start to achieve weight-bearing locomotion. In association with the progression of weight-bearing locomotion there are presumed developmental changes in the intrinsic electrical properties of spinal -motoneurons. However, these developmental changes in the properties of -motoneuron properties have not been systematically explored in mice. Here, data are presented documenting the developmental changes of selected intrinsic motoneuron electrical properties, including statistically significant changes in action potential half-width, intrinsic excitability and diversity (quantified as coefficient of variation) of rheobase current, afterhyperpolarization half-decay time, and input resistance. In various adult mammalian preparations, the maintenance of intrinsic motoneuron electrical properties is dependent on activity and/or transmission-sensitive motoneuron-muscle interactions. In this study, we show that botulinum toxin-induced muscle paralysis led to statistically significant changes in the normal development of intrinsic motoneuron electrical properties in the postnatal mouse. This suggests that muscle activity during early neonatal life contributes to the development of normal motoneuron electrical properties.

  18. Lipofuscin-like pigments in the rat heart during early postnatal development: effect of selenium supplementation

    Czech Academy of Sciences Publication Activity Database

    Ošťádalová, Ivana; Charvátová, Zuzana; Wilhelm, J.

    2010-01-01

    Roč. 59, č. 6 (2010), s. 881-886 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : early postnatal development * heart * lipofuscin-like pigment * selenium * reactive oxygen species Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.646, year: 2010

  19. Galectin-1 is expressed in early-type neural progenitor cells and down-regulates neurogenesis in the adult hippocampus

    Directory of Open Access Journals (Sweden)

    Imaizumi Yoichi

    2011-01-01

    Full Text Available Abstract Background In the adult mammalian brain, neural stem cells (NSCs proliferate in the dentate gyrus (DG of the hippocampus and generate new neurons throughout life. A multimodal protein, Galectin-1, is expressed in neural progenitor cells (NPCs and implicated in the proliferation of the NPCs in the DG. However, little is known about its detailed expression profile in the NPCs and functions in adult neurogenesis in the DG. Results Our immunohistochemical and morphological analysis showed that Galectin-1 was expressed in the type 1 and 2a cells, which are putative NSCs, in the subgranular zone (SGZ of the adult mouse DG. To study Galectin-1's function in adult hippocampal neurogenesis, we made galectin-1 knock-out mice on the C57BL6 background and characterized the effects on neurogenesis. In the SGZ of the galectin-1 knock-out mice, increased numbers of type 1 cells, DCX-positive immature progenitors, and NeuN-positive newborn neurons were observed. Using triple-labeling immunohistochemistry and morphological analyses, we found that the proliferation of the type-1 cells was increased in the SGZ of the galectin-1 knock-out mice, and we propose that this proliferation is the mechanism for the net increase in the adult neurogenesis in these knock-out mice DG. Conclusions Galectin-1 is expressed in the neural stem cells and down-regulates neurogenesis in the adult hippocampus.

  20. [Effects and consequence of recurrent seizures of neonatal rat on the hippocampal neurogenesis].

    Science.gov (United States)

    Shi, Xiu-yu; Wang, Ji-wen; Sun, Ruo-peng

    2006-04-01

    Seizures occur more frequently in the neonatal period than at any other time in life. A controversy which has been debated for the recent years is whether recurrent neonatal seizures can lead to long-term adverse consequences or are simply a reflection of underlying brain dysfunction and are not intrinsically harmful. Despite numerous clinical observations showed that seizures may be detrimental to the developing brain, the pathological mechanism has not yet been completely understood. The goal of this study was to investigate what effect was induced by recurrent seizures in neonatal rats on dentate granule cell neurogenesis. Sixty-four neonatal Wistar rats were randomly divided into seizure group (n = 40) and control group (n = 24). The rats of seizure group were subjected to three times of pilocarpine injections intraperitonealy at postnatal day 1 (P1), 4 (P4) and 7 (P7). Neonatal rats of the control group were given saline injection (i.p.) at the same time points. The rat were sacrificed separately at the next four time points: immediately after the third seizure (P7), the fourth day after the seizure (P11), the fourteenth day (P21) and the forty fifth day (P52), corresponding control group rats were killed accordingly. The rats in both seizure and control groups were given bromodeoxyuridine (BrdU) injection 36 hours before sacrifice to indicate newly generated cells. Brain tissue sections were prepared and subjected to Nissl staining for neuronal loss, by BrdU labeling for cell proliferation and by BrdU + NF200 (neurofilament 200) double labeling for the identification of the newly formed cells. The numbers of BrdU-labeled cells were age-dependent in the control group, decreased with age, and their morphorlogy and distribution changed (P < 0.01). BrdU-labeled cells decreased significantly in the seizure group compared with the matched controls at P7 and P11 (P < 0.01), while at P21 there was no significant difficence between the two groups. On the contrary, Brd

  1. Depleting adult dentate gyrus neurogenesis increases cocaine-seeking behavior.

    Science.gov (United States)

    Deroche-Gamonet, Véronique; Revest, Jean-Michel; Fiancette, Jean-François; Balado, Eric; Koehl, Muriel; Grosjean, Noëlle; Abrous, Djoher Nora; Piazza, Pier-Vincenzo

    2018-03-05

    The hippocampus is the main locus for adult dentate gyrus (DG) neurogenesis. A number of studies have shown that aberrant DG neurogenesis correlates with many neuropsychiatric disorders, including drug addiction. Although clear causal relationships have been established between DG neurogenesis and memory dysfunction or mood-related disorders, evidence of the causal role of DG neurogenesis in drug-seeking behaviors has not been established. Here we assessed the role of new DG neurons in cocaine self-administration using an inducible transgenic approach that selectively depletes adult DG neurogenesis. Our results show that transgenic mice with decreased adult DG neurogenesis exhibit increased motivation to self-administer cocaine and a higher seeking response to cocaine-related cues. These results identify adult hippocampal neurogenesis as a key factor in vulnerability to cocaine addiction.

  2. Factors That Modulate Neurogenesis: A Top-Down Approach.

    Science.gov (United States)

    LaDage, Lara D

    2016-08-24

    Although hippocampal neurogenesis in the adult brain has been conserved across the vertebrate lineage, laboratory studies have primarily examined this phenomenon in rodent models. This approach has been successful in elucidating important factors and mechanisms that can modulate rates of hippocampal neurogenesis, including hormones, environmental complexity, learning and memory, motor stimulation, and stress. However, recent studies have found that neurobiological research on neurogenesis in rodents may not easily translate to, or explain, neurogenesis patterns in nonrodent systems, particularly in species examined in the field. This review examines some of the evolutionary and ecological variables that may also modulate neurogenesis patterns. This 'top-down' and more naturalistic approach, which incorporates ecology and natural history, particularly of nonmodel species, may allow for a more comprehensive understanding of the functional significance of neurogenesis. © 2016 S. Karger AG, Basel.

  3. Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal

    Science.gov (United States)

    Hanson, Nicola D; Owens, Michael J; Nemeroff, Charles B

    2011-01-01

    The neurogenesis hypothesis of depression posits (1) that neurogenesis in the subgranular zone of the dentate gyrus is regulated negatively by stressful experiences and positively by treatment with antidepressant drugs and (2) that alterations in the rate of neurogenesis play a fundamental role in the pathology and treatment of major depression. This hypothesis is supported by important experimental observations, but is challenged by equally compelling contradictory reports. This review summarizes the phenomenon of adult hippocampal neurogenesis, the initial and continued evidence leading to the development of the neurogenesis hypothesis of depression, and the recent studies that have disputed and/or qualified those findings, to conclude that it can be affected by stress and antidepressants under certain conditions, but that these effects do not appear in all cases of psychological stress, depression, and antidepressant treatment. PMID:21937982

  4. Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity.

    Science.gov (United States)

    Slidsborg, Carina; Jensen, Louise Bering; Rasmussen, Steen Christian; Fledelius, Hans Callø; Greisen, Gorm; Cour, Morten de la

    2018-01-01

    To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP). This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national registers were searched, and data were linked through a unique civil registration number. The study sample consisted of 106 cases each matched with two comparison infants. Matching criteria were gestational age (GA) at birth, ROP not registered and born at the same neonatal intensive care unit. Potential 'new' risk factors were analysed in a multivariate logistic regression model, while adjusted for previously recognised risk factors (ie, GA at birth, small for gestational age, multiple birth and male sex). Hospital records of 310 preterm infants (106 treated; 204 comparison infants) were available. Nutrition in terms of energy (kcal/kg/week) and protein (g/kg/week) given to the preterm infants during the first postnatal week were statistically insignificant between the study groups (Mann-Whitney U test; p=0.165/p=0.163). Early postnatal weight gain between the two study groups was borderline significant (t-test; p=0.047). Hyperglycaemic events (indexed value) were statistically significantly different between the two study groups (Mann-Whitney U test; p<0.001). Hyperglycaemia was a statistically independent risk factor (OR: 1.022; 95% CI 1.002 to 1.042; p=0.031). An independent association was found between the occurrence of hyperglycaemic events during the first postnatal week and later development of treatment-demanding ROP, when adjusted for known risk factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Detrimental effects of physical inactivity on neurogenesis

    Directory of Open Access Journals (Sweden)

    Trenton Lippert

    2016-01-01

    Full Text Available Patients diagnosed with neurological disorders exhibit a variety of physical and psychiatric symptoms, including muscle atrophy, general immobility, and depression. Patients who participate in physical rehabilitation at times show unexpected clinical improvement, which includes diminished depression and other stress-related behaviors. Regenerative medicine has advanced two major stem cell-based therapies for central nervous system (CNS disorders, transplantation of exogenous stem cells, and enhancing the endogenous neurogenesis. The latter therapy utilizes a natural method of re-innervating the injured brain, which may mend neurological impairments. In this study, we examine how inactivity-induced atrophy, using the hindlimb suspension model, alters neurogenesis in rats. The hypothesis is that inactivity inhibits neurogenesis by decreasing circulation growth or trophic factors, such as vascular endothelial growth or neurotrophic factors. The restriction modifies neurogenesis and stem cell differentiation in the CNS, the stem cell microenvironment is examined by the trophic and growth factors, including stress-related proteins. Despite growing evidence revealing the benefits of "increased" exercise on neurogenesis, the opposing theory involving "physical inactivity," which simulates pathological states, continues to be neglected. This novel theory will allow us to explore the effects on neurogenesis by an intransigent stem cell microenvironment likely generated by inactivity. 5-bromo-2-deoxyuridine labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid, and brain levels of trophic factors, growth factors, and stress-related proteins are suggested identifiers of neurogenesis, while evaluation of spontaneous movements will give insight into the psychomotor effects of inactivity. Investigations devised to show how in vivo stimulation, or lack thereof, affects the stem cell microenvironment are necessary to establish

  6. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment.

    Science.gov (United States)

    Feng, Shufang; Shi, Tianyao; Qiu, Jiangxia; Yang, Haihong; Wu, Yan; Zhou, Wenxia; Wang, Wei; Wu, Haitao

    2017-10-01

    It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. Using a genetic approach to selectively ablate Notch1 signaling in late immature precursors in the postnatal hippocampus by cross-breeding doublecortin (DCX) + neuron-specific proopiomelanocortin (POMC)-α Cre mice with floxed Notch1 mice, we demonstrated a previously unreported pivotal role of Notch1 signaling in survival and function of adult newborn neurons in the dentate gyrus. Moreover, behavioral and functional studies demonstrated that POMC-Notch1 -/- mutant mice showed anxiety and depressive-like behavior with impaired synaptic transmission properties in the dentate gyrus. Finally, our mechanistic study showed significantly compromised phosphorylation of cAMP response element-binding protein (CREB) in Notch1 mutants, suggesting that the dysfunction of Notch1 mutants is associated with the disrupted pCREB signaling in postnatally generated immature neurons in the dentate gyrus.-Feng, S., Shi, T., Qiu, J., Yang, H., Wu, Y., Zhou, W., Wang, W., Wu, H. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment. © FASEB.

  7. Enhanced post-ischemic neurogenesis in aging rats

    Directory of Open Access Journals (Sweden)

    Yao-Fang Tan

    2010-08-01

    Full Text Available Hippocampal neurogenesis persists in adult mammals, but its rate declines dramatically with age. Evidence indicates that experimentally-reduced levels of neurogenesis (e.g. by irradiation in young rats has profound influence on cognition as determined by learning and memory tests. In the present study we asked whether in middle-aged, 10-13 months old rats, cell production can be restored towards the level present in young rats. To manipulate neurogenesis we induced bilateral carotid occlusion with hypotension. This procedure is known to increase neurogenesis in young rats, presumably in a compensatory manner, but until now, has never been tested in aging rats. Cell production was measured at 10, 35 and 90 days after ischemia. The results indicate that neuronal proliferation and differentiation can be transiently restored in middle-aged rats. Furthermore, the effects are more pronounced in the dorsal as opposed to ventral hippocampus thus restoring the dorso-ventral gradient seen in younger rats. Our results support previous findings showing that some of the essential features of the age-dependent decline in neurogenesis are reversible. Thus, it may be possible to manipulate neurogenesis and improve learning and memory in old age.

  8. Women's views of postnatal care in the context of the increasing pressure on postnatal beds in Australia.

    Science.gov (United States)

    McLachlan, Helen L; Gold, Lisa; Forster, Della A; Yelland, Jane; Rayner, Joanne; Rayner, Sharon

    2009-12-01

    Despite limited evidence evaluating early postnatal discharge, length of hospital stay has declined dramatically in Australia since the 1980s. The recent rising birth rate in Victoria, Australia has increased pressure on hospital beds, and many services have responded by discharging women earlier than planned, often with little preparation during pregnancy. We aimed to explore the views of women and their partners regarding a number of theoretical postnatal care 'packages' that could provide an alternative approach to early postnatal care. Eight focus groups and four interviews were held in rural and metropolitan Victoria in 2006 with participants who had experienced a mix of public and private maternity care. These included 8 pregnant women, 42 recent mothers and 2 male partners. All were fluent in English. Focus groups explored participants' experiences and/or expectations of early postnatal care in hospital and at home and their views of alternative packages of postnatal care where location of care shifted from hospital to home and/or hotel. This paper describes the packages and explores and describes what 'value' women placed on the various components of care. Overall, women expressed a preference for what they had experienced or expected, which may be explained by the 'what is must be best' phenomenon where women place value on the status quo. They generally did not respond favourably towards the alternative postnatal care packages, with concerns about any shorter length of hospital stay, especially for first time mothers. Women were concerned about the safety and wellbeing of their new baby and reported that they lacked confidence in their ability to care for their baby. The physical presence and availability of professional support was seen to alleviate these concerns, especially for first time mothers. Participants did not believe that increased domiciliary visits compensated for forgoing the perceived security and value of staying in hospital. Women

  9. Adult Neurogenesis Supports Short-Term Olfactory Memory

    OpenAIRE

    Arenkiel, Benjamin R.

    2010-01-01

    Adult neurogenesis has captivated neuroscientists for decades, with hopes that understanding the programs underlying this phenomenon may provide unique insight toward avenues for brain repair. Interestingly, however, despite intense molecular and cellular investigation, the evolutionary roles and biological functions for ongoing neurogenesis have remained elusive. Here I review recent work published in the Journal of Neuroscience that reveals a functional role for continued neurogenesis towar...

  10. Adult hippocampal neurogenesis in natural populations of mammals.

    Science.gov (United States)

    Amrein, Irmgard

    2015-05-01

    This review will discuss adult hippocampal neurogenesis in wild mammals of different taxa and outline similarities with and differences from laboratory animals. It begins with a review of evidence for hippocampal neurogenesis in various mammals, and shows the similar patterns of age-dependent decline in cell proliferation in wild and domesticated mammals. In contrast, the pool of immature neurons that originate from proliferative activity varies between species, implying a selective advantage for mammals that can make use of a large number of these functionally special neurons. Furthermore, rapid adaptation of hippocampal neurogenesis to experimental challenges appears to be a characteristic of laboratory rodents. Wild mammals show species-specific, rather stable hippocampal neurogenesis, which appears related to demands that characterize the niche exploited by a species rather than to acute events in the life of its members. Studies that investigate adult neurogenesis in wild mammals are not numerous, but the findings of neurogenesis under natural conditions can provide new insights, and thereby also address the question to which cognitive demands neurogenesis may respond during selection. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  11. Polyphenols and IUGR pregnancies: Maternal hydroxytyrosol supplementation improves prenatal and early-postnatal growth and metabolism of the offspring.

    Directory of Open Access Journals (Sweden)

    Marta Vazquez-Gomez

    Full Text Available Hydroxytyrosol is a polyphenol with antioxidant, metabolism-regulatory, anti-inflammatory and immuno-modulatory properties. The present study aimed to determine whether supplementing the maternal diet with hydroxytyrosol during pregnancy can improve pre- and early post-natal developmental patterns and metabolic traits of the offspring. Experiment was performed in Iberian sows fed a restricted diet in order to increase the risk of IUGR. Ten sows were treated daily with 1.5 mg of hydroxytyrosol per kg of feed between Day 35 of pregnancy (30% of total gestational period until delivery whilst 10 animals were left untreated as controls. Number and weight of offspring were assessed at birth, on post-natal Day 15 and at weaning (25 days-old. At weaning, body composition and plasma indexes of glucose and lipids were measured. Treatment with hydroxytyrosol was associated with higher mean birth weight, lower incidence of piglets with low birth weight. Afterwards, during the lactation period, piglets in the treated group showed a higher body-weight than control piglets; such effects were even stronger in the most prolific litters. These results suggest that maternal supplementation with hydroxytyrosol may improve pre- and early post-natal development of offspring in pregnancies at risk of IUGR.

  12. Detrimental role of prolonged sleep deprivation on adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Carina eFernandes

    2015-04-01

    Full Text Available Adult mammalian brains continuously generate new neurons, a phenomenon called neurogenesis. Both environmental stimuli and endogenous factors are important regulators of neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and neurogenesis in brain function, such as learning, memory and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on neurogenesis.

  13. Adult neurogenesis supports short-term olfactory memory.

    Science.gov (United States)

    Arenkiel, Benjamin R

    2010-06-01

    Adult neurogenesis has captivated neuroscientists for decades, with hopes that understanding the programs underlying this phenomenon may provide unique insight toward avenues for brain repair. Interestingly, however, despite intense molecular and cellular investigation, the evolutionary roles and biological functions for ongoing neurogenesis have remained elusive. Here I review recent work published in the Journal of Neuroscience that reveals a functional role for continued neurogenesis toward forming short-term olfactory memories.

  14. An association of adult personality with prenatal and early postnatal growth

    DEFF Research Database (Denmark)

    Flensborg-Madsen, Trine; Revsbech, Rasmus; Sørensen, Holger Jelling

    2014-01-01

    Abstract Background: Recent studies have noted differences in social acquiescence and interpersonal relations among adults born preterm or with very low birth weight compared to full term adults. In addition, birth weight has been observed to be negatively correlated with lie-scale scores in two ...... influence of prenatal and early postnatal development on personality growth and development. Keywords: Eysenck personality questionnaire, Lie-scale, Extraversion, Neuroticism, Psychoticism, Birth weight, Birth length, Birth head-circumference...... individuals participated in a follow-up at 20–34 years and was administered the Eysenck Personality Questionnaire (EPQ) which includes a lie-scale (indicating social acquiescence or self-insight). Associations between lie-scale scores and weight, length and head circumference respectively were analysed...

  15. Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation

    Directory of Open Access Journals (Sweden)

    Sissel J. Moltu

    2014-05-01

    Full Text Available Objectives: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight < 1500 g randomized to an enhanced or a standard diet during neonatal hospitalization. Methods: Metabolomics using nuclear magnetic resonance spectroscopy (NMR was conducted on urine samples obtained during the first week of life and thereafter fortnightly. Results: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate. The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight < 10th percentile for gestational age as compared to the appropriate for gestational age infants. Conclusion: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype.

  16. High post-partum levels of corticosterone given to dams influence postnatal hippocampal cell proliferation and behavior of offspring: A model of post-partum stress and possible depression.

    Science.gov (United States)

    Brummelte, Susanne; Pawluski, Jodi L; Galea, Liisa A M

    2006-09-01

    Post-partum stress and depression (PPD) have a significant effect on child development and behavior. Depression is associated with hypercortisolism in humans, and the fluctuating levels of hormones, including corticosterone, during pregnancy and the post-partum, may contribute to PPD. The present study was developed to investigate the effects of high-level corticosterone (CORT) post-partum in the mother on postnatal neurogenesis and behavior in the offspring. Sprague-Dawley dams were treated with either CORT (40 mg/kg) or sesame oil injections daily for 26 days beginning the day after giving birth. Dams were tested in the forced swim test (FST) and in the open field test (OFT) on days 24-26 post-partum. Results showed that the dams exposed to CORT expressed "depressive-like" behavior compared to controls, with decreased struggling behavior and increased immobility in the FST. To investigate the effects of treatment on hippocampal postnatal cell proliferation and survival in the offspring, males and females from treated dams were injected with BrdU (50 mg/kg) on postnatal day 21 and perfused either 24 h (cell proliferation) or 21 days (cell survival) later. Furthermore, male and female offspring from each litter were tested in adulthood on various behavioral tests, including the forced swim test, open field test, resistance to capture test and elevated plus maze. Intriguingly, male, but not female, offspring of CORT-treated dams exhibited decreased postnatal cell proliferation in the dentate gyrus. Both male and female offspring of CORT-treated dams showed higher resistance to capture and greater locomotor activity as assessed in the open field test. As high levels of CORT may be a characteristic of stress and/or depression, these findings support a model of 'CORT-induced' post-partum stress and possibly depression and demonstrate that the offspring of affected dams can exhibit changes in postnatal neurogenesis and behavior in adulthood.

  17. Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin

    Directory of Open Access Journals (Sweden)

    Eisch Amelia

    2010-01-01

    Full Text Available Abstract Background Survivin is a unique member of the inhibitor of apoptosis protein (IAP family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated. Results To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ and the subgranular zone (SGZ. We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (SurvivinCamcre with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. SurvivinCamcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning. Conclusions The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.

  18. Is forebrain neurogenesis a potential repair mechanism after stroke?

    OpenAIRE

    Inta, Dragos; Gass, Peter

    2015-01-01

    The use of adult subventricular zone (SVZ) neurogenesis as brain repair strategy after stroke represents a hot topic in neurologic research. Recent radiocarbon-14 dating has revealed a lack of poststroke neurogenesis in the adult human neocortex; however, adult neurogenesis has been shown to occur, even under physiologic conditions, in the human striatum. Here, these results are contrasted with experimental poststroke neurogenesis in the murine brain. Both in humans and in rodents, the SVZ ge...

  19. The Tlx gene regulates the timing of neurogenesis in the cortex.

    Science.gov (United States)

    Roy, Kristine; Kuznicki, Kathleen; Wu, Qiang; Sun, Zhuoxin; Bock, Dagmar; Schutz, Gunther; Vranich, Nancy; Monaghan, A Paula

    2004-09-22

    The tailless (tlx) gene is a forebrain-restricted transcription factor. Tlx mutant animals exhibit a reduction in the size of the cerebral hemispheres and associated structures (Monaghan et al., 1997). Superficial cortical layers are specifically reduced, whereas deep layers are relatively unaltered (Land and Monaghan, 2003). To determine whether the adult laminar phenotype has a developmental etiology and whether it is associated with a change in proliferation/differentiation decisions, we examined the cell cycle and neurogenesis in the embryonic cortex. We found that there is a temporal and regional requirement for the Tlx protein in progenitor cells (PCs). Neurons prematurely differentiate at all rostrocaudal levels up to mid-neurogenesis in mutant animals. Heterozygote animals have an intermediate phenotype indicating there is a threshold requirement for Tlx in early cortical neurogenesis. Our studies indicate that PCs in the ventricular zone are sensitive to loss of Tlx in caudal regions only; however, PCs in the subventricular zone are altered at all rostrocaudal levels in tlx-deficient animals. Furthermore, we found that the cell cycle is shorter from embryonic day 9.5 in tlx-/- embryos. At mid-neurogenesis, the PC population becomes depleted, and late PCs have a longer cell cycle in tlx-deficient animals. Consequently, later generated structures, such as upper cortical layers, the dentate gyrus, and the olfactory bulbs, are severely reduced. These studies indicate that tlx is an essential intrinsic regulator in the decision to proliferate or differentiate in the developing forebrain.

  20. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

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    Lorena Varela-Nallar

    2015-01-01

    Full Text Available Andrographolide (ANDRO is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β, a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer’s disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected.

  1. Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism

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    Chomiak Taylor

    2010-08-01

    Full Text Available Abstract Background Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking. Results We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA in vivo. Brain sections obtained from postnatal rat pups treated with VPA in vivo revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour. Conclusions The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.

  2. Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function.

    Science.gov (United States)

    Poulose, Shibu M; Miller, Marshall G; Scott, Tammy; Shukitt-Hale, Barbara

    2017-11-01

    Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plasticity, brain homeostasis, and maintenance in the central nervous system and is a crucial factor in preserving the cognitive function and repair of damaged brain cells affected by aging and brain disorders. Intrinsic factors such as aging, neuroinflammation, oxidative stress, and brain injury, as well as lifestyle factors such as high-fat and high-sugar diets and alcohol and opioid addiction, negatively affect adult neurogenesis. Conversely, many dietary components such as curcumin, resveratrol, blueberry polyphenols, sulforaphane, salvionic acid, polyunsaturated fatty acids (PUFAs), and diets enriched with polyphenols and PUFAs, as well as caloric restriction, physical exercise, and learning, have been shown to induce neurogenesis in adult brains. Although many of the underlying mechanisms by which nutrients and dietary factors affect adult neurogenesis have yet to be determined, nutritional approaches provide promising prospects to stimulate adult neurogenesis and combat neurodegenerative diseases and cognitive decline. In this review, we summarize the evidence supporting the role of nutritional factors in modifying adult neurogenesis and their potential to preserve cognitive function during aging. © 2017 American Society for Nutrition.

  3. Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

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    Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

    2014-01-01

    Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequentl...

  4. Early metabolic programming of puberty onset: impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system

    DEFF Research Database (Denmark)

    Castellano, Juan M; Bentsen, Agnete H; Sánchez-Garrido, Miguel A

    2011-01-01

    the timing of puberty; however, the potential underlying mechanisms remain poorly defined. Here we report how changes in the pattern of postnatal feeding affect the onset of puberty and evaluate key hormonal and neuropeptide [Kiss1/kisspeptin (Kp)] alterations linked to these early nutritional manipulations...... of puberty, together with higher levels of leptin and hypothalamic Kiss1 mRNA. Conversely, postnatal underfeeding caused a persistent reduction in body weight, lower ovarian and uterus weights, and delayed vaginal opening, changes that were paralleled by a decrease in leptin and Kiss1 mRNA levels. Kisspeptin...... at puberty were similar in all groups, except for enhanced responsiveness to low doses of Kp-10 in postnatally underfed rats. In conclusion, our data document that the timing of puberty is sensitive to both overfeeding and subnutrition during early (postnatal) periods and suggest that alterations...

  5. Effect of early postnatal exposure to valproate on neurobehavioral development and regional BDNF expression in two strains of mice.

    Science.gov (United States)

    Bath, Kevin G; Pimentel, Tiare

    2017-05-01

    Valproate has been used for over 30years as a first-line treatment for epilepsy. In recent years, prenatal exposure to valproate has been associated with teratogenic effects, limiting its use in women that are pregnant or of childbearing age. However, despite its potential detrimental effects on development, valproate continues to be prescribed at high rates in pediatric populations in some countries. Animal models allow us to test hypotheses regarding the potential effects of postnatal valproate exposure on neurobehavioral development, as well as identify potential mechanisms mediating observed effects. Here, we tested the effect of early postnatal (P4-P11) valproate exposure (100mg/kg and 200mg/kg) on motor and affective development in two strains of mice, SVE129 and C57Bl/6N. We also assessed the effect of early valproate exposure on regional BDNF protein levels, a potential target of valproate, and mediator of neurodevelopmental outcomes. We found that early life valproate exposure led to significant motor impairments in both SVE129 and C57Bl/6N mice. Both lines of mice showed significant delays in weight gain, as well as impairments in the righting reflex (P7-8), wire hang (P17), open field (P12 and P21), and rotarod (P25 and P45) tasks. Interestingly, some of the early locomotor effects were strain- and dose-dependent. We observed no effects of valproate on early markers of anxiety-like behavior. Importantly, early life valproate exposure had significant effects on regional BDNF expression, leading to a near 50% decrease in BDNF levels in the cerebellum of both strains of mice, while not impacting hippocampal BDNF protein levels. These observations indicate that postnatal exposure to valproate may have significant, and region-specific effects, on neural and behavioral development, with specific consequences for cerebellar development and motor function. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence.

    Science.gov (United States)

    Rayen, Ine; van den Hove, Daniël L; Prickaerts, Jos; Steinbusch, Harry W; Pawluski, Jodi L

    2011-01-01

    Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity.

  7. Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence.

    Directory of Open Access Journals (Sweden)

    Ine Rayen

    Full Text Available Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day or vehicle beginning on postnatal day 1 (P1. Adolescent male and female offspring were divided into 4 groups: 1 prenatal stress+fluoxetine exposure, 2 prenatal stress+vehicle, 3 fluoxetine exposure alone, and 4 vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity.

  8. Linking adult olfactory neurogenesis to social behavior

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    Claudia E Feierstein

    2012-11-01

    Full Text Available In the adult brain, new neurons are added to two brain areas: the olfactory bulb and the hippocampus. Newly-generated neurons integrate into the preexisting circuits, bringing a set of unique properties, such as increased plasticity and responsiveness to stimuli. However, the functional implications of the constant addition of these neurons remain unclear, although they are believed to be important for learning and memory. The levels of neurogenesis are regulated by a variety of environmental factors, as well as during learning, suggesting that new neurons could be important for coping with changing environmental demands. Notably, neurogenesis has been shown to be physiologically regulated in relation to reproductive behavior: neurogenesis increases in female mice upon exposure to cues of the mating partners, during pregnancy and lactation, and in male mice upon exposure to their offspring. In this scenario, and because of the key contribution of olfaction to maternal behavior, we sought to investigate the contribution of adult-generated neurons in the olfactory system to maternal behavior and offspring recognition. To do so, we selectively disrupted neurogenesis in the olfactory pathway of female mice using focal irradiation. Disruption of adult neurogenesis in the olfactory bulb did not affect maternal behavior, or the ability of female mice to discriminate familiar from unfamiliar pups. However, reduction of olfactory neurogenesis resulted in abnormal social interaction of female mice, specifically with male conspecifics. Because the olfactory system is crucial for sex recognition, we suggest that the abnormal interaction with males could result from the inability to detect or discriminate male-specific odors and could therefore have implications for the recognition of potential mating partners. Here, I review the results of this and other studies, and discuss their implications for our understanding of the function of adult neurogenesis.

  9. Persistent Adult Neuroimmune Activation and Loss of Hippocampal Neurogenesis Following Adolescent Ethanol Exposure: Blockade by Exercise and the Anti-inflammatory Drug Indomethacin

    Directory of Open Access Journals (Sweden)

    Ryan P. Vetreno

    2018-03-01

    Full Text Available Alcohol abuse and binge drinking are common during adolescence, a developmental period characterized by heightened neuroplasticity. Animal studies reveal that adolescent ethanol exposure decreases hippocampal neurogenesis that persists into adulthood, but the mechanism remains to be fully elucidated. Using a rodent model of adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-days on/2-days off from postnatal day [P]25 to P55, we tested the hypothesis that AIE-induced upregulation of neuroimmune signaling contributes to the loss of hippocampal neurogenesis in adulthood. We found that AIE caused upregulation of multiple proinflammatory Toll-like receptors (TLRs, increased expression of phosphorylated NF-κB p65 (pNF-κB p65 and the cell death marker cleaved caspase 3, and reduced markers of neurogenesis in the adult (P80 hippocampus, which is consistent with persistently increased neuroimmune signaling reducing neurogenesis. We observed a similar increase of pNF-κB p65-immunoreactive cells in the post-mortem human alcoholic hippocampus, an effect that was negatively correlated with age of drinking onset. Voluntary wheel running from P24 to P80 prevented the AIE-induced loss of neurogenesis markers (i.e., nestin and doublecortin in the adult hippocampus that was paralleled by blockade of increased expression of the cell death marker cleaved caspase 3. Wheel running also prevented the AIE-induced increase of hippocampal pNF-κB p65 and induction of neuroimmune NF-κB target genes, including TNFα and IκBα in the adult brain. Administration of the anti-inflammatory drug indomethacin during AIE prevented the loss of neurogenesis markers (i.e., nestin and doublecortin and the concomitant increase of cleaved caspase 3, an effect that was accompanied by blockade of the increase of pNF-κB p65. Similarly, administration of the proinflammatory TLR4 activator lipopolysaccharide resulted in a loss of doublecortin that was paralleled by increased

  10. D-serine increases adult hippocampal neurogenesis

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    Sebastien eSultan

    2013-08-01

    Full Text Available Adult hippocampal neurogenesis results in the continuous formation of new neurons and is a process of brain plasticity involved in learning and memory. The neurogenic niche regulates the stem cell proliferation and the differentiation and survival of new neurons and a major contributor to the neurogenic niche are astrocytes. Among the molecules secreted by astrocytes, D-serine is an important gliotransmitter and is a co-agonist of the glutamate, N-methyl-D-aspartate (NMDA receptor. D-serine has been shown to enhance the proliferation of neural stem cells in vitro, but its effect on adult neurogenesis in vivo is unknown. Here, we tested the effect of exogenous administration of D-serine on adult neurogenesis in the mouse dentate gyrus. We found that 1 week of treatment with D-serine increased cell proliferation in vivo and in vitro and increased the density of neural stem cells and transit amplifying progenitors. Furthermore, D-serine increased the survival of newborn neurons. Together, these results indicate that D-serine treatment resulted in the improvement of several steps of adult neurogenesis in vivo.

  11. Hippocampal Neurogenesis and the Brain Repair Response to Brief Stereotaxic Insertion of a Microneedle

    Directory of Open Access Journals (Sweden)

    Shijie Song

    2013-01-01

    Full Text Available We tested the hypothesis that transient microinjury to the brain elicits cellular and humoral responses that stimulate hippocampal neurogenesis. Brief stereotaxic insertion and removal of a microneedle into the right hippocampus resulted in (a significantly increased expression of granulocyte-colony stimulating factor (G-CSF, the chemokine MIP-1a, and the proinflammatory cytokine IL12p40; (b pronounced activation of microglia and astrocytes; and (c increase in hippocampal neurogenesis. This study describes immediate and early humoral and cellular mechanisms of the brain’s response to microinjury that will be useful for the investigation of potential neuroprotective and deleterious effects of deep brain stimulation in various neuropsychiatric disorders.

  12. Neurotransmitter regulation of adult neurogenesis: putative therapeutic targets.

    Science.gov (United States)

    Vaidya, V A; Vadodaria, K C; Jha, S

    2007-10-01

    The evidence that new neuron addition takes place in the mammalian brain throughout adult life has dramatically altered our perspective of the potential for plasticity in the adult CNS. Although several recent reports suggest a latent neurogenic capacity in multiple brain regions, the two major neurogenic niches that retain the ability to generate substantial numbers of new neurons in adult life are the subventricular zone (SVZ) lining the lateral ventricles and the subgranular zone (SGZ) in the hippocampal formation. The discovery of adult neurogenesis has also unveiled a novel therapeutic target for the repair of damaged neuronal circuits. In this regard, understanding the endogenous mechanisms that regulate adult neurogenesis holds promise both for a deeper understanding of this form of structural plasticity, as well as the identification of pathways that can serve as therapeutic targets to manipulate adult neurogenesis. The purpose of the present review is to discuss the regulation of adult neurogenesis by neurotransmitters and to highlight the relevance of these endogenous regulators as targets to modulate adult neurogenesis in a clinical context.

  13. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    Energy Technology Data Exchange (ETDEWEB)

    Khodanovich, M. Yu., E-mail: khodanovich@mail.tsu.ru [Tomsk State University, Research Institute of Biology and Biophysics, Laboratory of Neurobiology (Russian Federation)

    2015-11-17

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  14. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    Science.gov (United States)

    Khodanovich, M. Yu.

    2015-11-01

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  15. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    International Nuclear Information System (INIS)

    Khodanovich, M. Yu.

    2015-01-01

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors

  16. Sex steroids and neurogenesis.

    Science.gov (United States)

    Heberden, Christine

    2017-10-01

    The brain has long been known as a dimorphic organ and as a target of sex steroids. It is also a site for their synthesis. Sex steroids in numerous ways can modify cerebral physiology, and along with many processes adult neurogenesis is also modulated by sex steroids. This review will focus on the effects of the main steroids, estrogens, androgens and progestogens, and unveil some aspects of their partly disclosed mechanisms of actions. Gonadal steroids act on different steps of neurogenesis: cell proliferation seems to be increased by estrogens only, while androgens and progestogens favor neuronal renewal by increasing cell survival; differentiation is a common target. Aging is characterized by a cognitive deficiency, paralleled by a decrease in the rate of neuronal renewal and in the levels of circulating gonadal hormones. Therefore, the effects of gonadal hormones on the aging brain are important to consider. The review will also be expanded to related molecules which are agonists to the nuclear receptors. Sex steroids can modify adult neuronal renewal and the extensive knowledge of their actions on neurogenesis is essential, as it can be a leading pathway to therapeutic perspectives. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Stage-dependent alterations of progenitor cell proliferation and neurogenesis in an animal model of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Vetreno, Ryan P; Klintsova, Anna; Savage, Lisa M

    2011-05-19

    Alcohol-induced Wernicke-Korsakoff syndrome (WKS) culminates in bilateral diencephalic lesion and severe amnesia. Using the pyrithiamine-induced thiamine deficiency (PTD) animal paradigm of WKS, our laboratory has demonstrated hippocampal dysfunction in the absence of gross anatomical pathology. Extensive literature has revealed reduced hippocampal neurogenesis following a neuropathological insult, which might contribute to hippocampus-based learning and memory impairments. Thus, the current investigation was conducted to determine whether PTD treatment altered hippocampal neurogenesis in a stage-dependent fashion. Male Sprague-Dawley rats were assigned to one of 4 stages of thiamine deficiency based on behavioral symptoms: pre-symptomatic stage, ataxic stage, early post-opisthotonus stage, or the late post-opisthotonus stage. The S-phase mitotic marker 5'-bromo-2'-deoxyuridine (BrdU) was administered at the conclusion of each stage following thiamine restoration and subjects were perfused 24 hours or 28 days after BrdU to assess cellular proliferation or neurogenesis and survival, respectively. Dorsal hippocampal sections were immunostained for BrdU (proliferating cell marker), NeuN (neurons), GFAP (astrocytes), Iba-1 (microglia), and O4 (oligodendrocytes). The PTD treatment increased progenitor cell proliferation and survival during the early post-opisthotonus stage. However, levels of neurogenesis were reduced during this stage as well as the late post-opisthotonus stage where there was also an increase in astrocytogenesis. The diminished numbers of newly generated neurons (BrdU/NeuN co-localization) was paralleled by increased BrdU cells that did not co-localize with any of the phenotypic markers during these later stages. These data demonstrate that long-term alterations in neurogenesis and gliogenesis might contribute to the observed hippocampal dysfunction in the PTD model and human WKS. Published by Elsevier B.V.

  18. Hypothalamic neurogenesis persists in the aging brain and is controlled by energy-sensing IGF-I pathway.

    Science.gov (United States)

    Chaker, Zayna; George, Caroline; Petrovska, Marija; Caron, Jean-Baptiste; Lacube, Philippe; Caillé, Isabelle; Holzenberger, Martin

    2016-05-01

    Hypothalamic tanycytes are specialized glial cells lining the third ventricle. They are recently identified as adult stem and/or progenitor cells, able to self-renew and give rise to new neurons postnatally. However, the long-term neurogenic potential of tanycytes and the pathways regulating lifelong cell replacement in the adult hypothalamus are largely unexplored. Using inducible nestin-CreER(T2) for conditional mutagenesis, we performed lineage tracing of adult hypothalamic stem and/or progenitor cells (HySC) and demonstrated that new neurons continue to be born throughout adult life. This neurogenesis was targeted to numerous hypothalamic nuclei and produced different types of neurons in the dorsal periventricular regions. Some adult-born neurons integrated the median eminence and arcuate nucleus during aging and produced growth hormone releasing hormone. We showed that adult hypothalamic neurogenesis was tightly controlled by insulin-like growth factors (IGF). Knockout of IGF-1 receptor from hypothalamic stem and/or progenitor cells increased neuronal production and enhanced α-tanycyte self-renewal, preserving this stem cell-like population from age-related attrition. Our data indicate that adult hypothalamus retains the capacity of cell renewal, and thus, a substantial degree of structural plasticity throughout lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Interstitial cells of the adult neocortical white matter are the remnant of the early generated subplate neuron population

    International Nuclear Information System (INIS)

    Chun, J.J.; Shatz, C.J.

    1989-01-01

    The postnatal fate of the first-generated neurons of the cat cerebral cortex was examined. These neurons can be identified uniquely by 3H-thymidine exposure during the week preceding the neurogenesis of cortical layer 6. Previous studies in which 3H-thymidine birthdating at embryonic day 27 (E27) was combined with immunohistochemistry have shown that these neurons are present in large numbers during fetal and early postnatal life within the subplate (future white matter), that they are immunoreactive for the neuron-specific protein MAP2 and for the putative neurotransmitters GABA, NPY, SRIF, and CCK. Here, the same techniques were used to follow the postnatal location and disappearance of the early generated subplate neuron population. At birth (P0), subplate neurons showing immunoreactivity for GABA, NPY, SRIF, or CCK are present in large numbers and at high density within the white matter throughout the neocortex, and the entire population can be observed as a dense MAP2-immunoreactive band situated beneath cortical layer 6. Between P0 and P401 (adulthood), the MAP2-immunostained band disappears so that comparatively few MAP2-immunoreactive neurons remain within the white matter. There is a corresponding decrease in the number and density of neurons stained with antibodies against neurotransmitters. In each instance, these neurons could be double-labeled by the administration of 3H-thymidine at E27, indicating that they are the remnants of the early generated subplate neuron population. The major period of decrease occurs during the first 4 postnatal weeks, and adult values are attained by 5 months. Within the white matter of the lateral gyrus (visual cortex), the density of immunostained neurons decreases dramatically: MAP2, 82%, SRIF, 81%, and NPY, 96%

  20. Cadmium inhibits neurogenesis in zebrafish embryonic brain development

    Energy Technology Data Exchange (ETDEWEB)

    Chow, Elly Suk Hen [Division of Biology, California Institute of Technology, 1200 California Boulevard, Pasadena, CA 91125 (United States); Hui, Michelle Nga Yu; Lin Chunchi [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China); Cheng Shukhan [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China)], E-mail: bhcheng@cityu.edu.hk

    2008-05-01

    Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis.

  1. Cadmium inhibits neurogenesis in zebrafish embryonic brain development

    International Nuclear Information System (INIS)

    Chow, Elly Suk Hen; Hui, Michelle Nga Yu; Lin Chunchi; Cheng Shukhan

    2008-01-01

    Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis

  2. Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Hiroshi Ueno

    2015-01-01

    Full Text Available Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28 or P58 on the density of parvalbumin (PV, calbindin (CB, and calretinin (CR neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6. Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity.

  3. Aminopropyl carbazole analogues as potent enhancers of neurogenesis.

    Science.gov (United States)

    Yoon, Hye Jin; Kong, Sun-Young; Park, Min-Hye; Cho, Yongsung; Kim, Sung-Eun; Shin, Jae-Yeon; Jung, Sunghye; Lee, Jiyoun; Farhanullah; Kim, Hyun-Jung; Lee, Jeewoo

    2013-11-15

    Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

    International Nuclear Information System (INIS)

    Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas

    2007-01-01

    Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of β-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/β-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity

  5. Implantation of Neuronal Stem Cells Enhances Object Recognition without Increasing Neurogenesis after Lateral Fluid Percussion Injury in Mice

    Directory of Open Access Journals (Sweden)

    Laura B. Ngwenya

    2018-01-01

    Full Text Available Cognitive deficits after traumatic brain injury (TBI are debilitating and contribute to the morbidity and loss of productivity of over 10 million people worldwide. Cell transplantation has been linked to enhanced cognitive function after experimental traumatic brain injury, yet the mechanism of recovery is poorly understood. Since the hippocampus is a critical structure for learning and memory, supports adult neurogenesis, and is particularly vulnerable after TBI, we hypothesized that stem cell transplantation after TBI enhances cognitive recovery by modulation of endogenous hippocampal neurogenesis. We performed lateral fluid percussion injury (LFPI in adult mice and transplanted embryonic stem cell-derived neural progenitor cells (NPC. Our data confirm an injury-induced cognitive deficit in novel object recognition, a hippocampal-dependent learning task, which is reversed one week after NPC transplantation. While LFPI alone promotes hippocampal neurogenesis, as revealed by doublecortin immunolabeling of immature neurons, subsequent NPC transplantation prevents increased neurogenesis and is not associated with morphological maturation of endogenous injury-induced immature neurons. Thus, NPC transplantation enhances cognitive recovery early after LFPI without a concomitant increase in neuron numbers or maturation.

  6. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

    International Nuclear Information System (INIS)

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-01-01

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3 + apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB + interneurons, although the number of reelin + interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of cholinergic

  7. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

  8. Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development

    Directory of Open Access Journals (Sweden)

    Mekayla A. Storer

    2018-05-01

    Full Text Available Summary: Circulating systemic factors can regulate adult neural stem cell (NSC biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6, since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools. : In this report, Storer and colleagues demonstrate that the circulating cytokine IL-6, which is elevated in humans in different pathological situations, can perturb neural stem cell biology after birth. They show that IL-6 signaling is essential for self-renewal and maintenance of post-natal and adult NSCs in the murine forebrain under normal homeostatic conditions. Keywords: interleukin-6, neural stem cell, adult neurogenesis, CNS cytokines, postnatal brain development, stem cell depletion, neural stem cell niche, circulating stem cell factors, olfactory bulb

  9. Postnatal BMI changes in children with different birthweights: A trial study for detecting early predictive factors for pediatric obesity

    Science.gov (United States)

    Nakagawa, Yuichi; Nakanishi, Toshiki; Satake, Eiichiro; Matsushita, Rie; Saegusa, Hirokazu; Kubota, Akira; Natsume, Hiromune; Shibata, Yukinobu; Fujisawa, Yasuko

    2018-01-01

    Abstract. The purpose of this study was to clarify the degree of early postnatal growth by birthweight and detect early predictive factors for pediatric obesity. Body mass index (BMI) and degree of obesity were examined in children in the fourth year of elementary school and second year of junior high school. Their BMI at birth and three years of age were also examined. Based on birthweight, participants were divided into three groups: low ( 3500 g). Furthermore, according to the degree of obesity, they were divided into two groups: obese (20% ≤) and non-obese (20% >). The change of BMI from birth to three years of age (ΔBMI) showed a strong inverse relationship with birthweight and was significantly different among the three birthweight groups (low > middle > high). The ΔBMI and BMI at three years of age were higher in obese than in non-obese children and showed significant positive correlations with the degree of obesity. Early postnatal growth might be determined by birthweight and was higher in obese than in non-obese children. The ΔBMI from birth to three years of age and BMI at age of three years could be predictive factors for pediatric obesity. PMID:29403153

  10. Of Mice and Men: Neurogenesis, Cognition and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Orly eLazarov

    2013-08-01

    Full Text Available Neural stem cells are maintained in the subgranular layer of the dentate gyrus and in the subventricular zone in the adult mammalian brain throughout life. Neurogenesis is continuous, but its extent is tightly regulated by environmental factors, behavior, hormonal state, age and brain health. Increasing evidence supports a role for new neurons in cognitive function in rodents. Recent evidence delineates potential significant differences between adult neurogenesis in rodents and humans. Being context-dependent, neurogenesis in the human brain might be manifested differently than in the rodent brain. Decline in neurogenesis may play a role in cognitive deterioration, leading to the development of progressive learning and memory disorders, such as Alzheimer’s disease. This review discusses the different observations concerning neurogenesis in the rodent and human brain, and their functional implications for the healthy and diseased brain.

  11. Risk factors for antenatal depression, postnatal depression and parenting stress

    Directory of Open Access Journals (Sweden)

    Milgrom Jeannette

    2008-04-01

    Full Text Available Abstract Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Methods Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program 1. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26–32 weeks gestation. A subsample of these women (N = 161 also completed questionnaires at 10–12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI. Results Regression analyses identified significant risk factors for the three outcome measures. (1. Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2. Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3. Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator

  12. Risk factors for antenatal depression, postnatal depression and parenting stress.

    Science.gov (United States)

    Leigh, Bronwyn; Milgrom, Jeannette

    2008-04-16

    Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program 1. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26-32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10-12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors. Risk factor profiles for

  13. Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats.

    Science.gov (United States)

    Ikeda, Naho; Shoji, Hiromichi; Suganuma, Hiroki; Ohkawa, Natsuki; Kantake, Masato; Murano, Yayoi; Sakuraya, Koji; Shimizu, Toshiaki

    2016-05-01

    Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period. © 2015 Japan Pediatric Society.

  14. Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function

    Science.gov (United States)

    Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plas...

  15. [The effect of birth weight on the early postnatal vitality of piglets].

    Science.gov (United States)

    Hoy, S; Lutter, C; Wähner, M; Puppe, B

    1994-10-01

    Investigations with 1248 newborn piglets in 7 farms showed a high significant influence of birth weight on parameters of early postnatal vitality. The duration between birth and first standing up was by two times, the time between birth and first udder contact by 3.5 times and the duration between birth and first colostrum intake was by 4 times longer in piglets with a low birth weight ( 2200 g). The drop in rectal temperature up to 30 minutes after birth reached 4.5 Kelvin in lightweight piglets, whereas their litter mates with a high body weight at birth had a value of 0.85 K (p vitality of newborn piglets and has a high prognostic value in relation to the risk of losses and the live weight development of neonates.

  16. Impairments in neurogenesis are not tightly linked to depressive behavior in a transgenic mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Daniel M Iascone

    Full Text Available Alzheimer's disease (AD, the most common cause of dementia, is also associated with depression. Although the precise mechanisms that lead to depression in AD are unknown, the impairments in adult hippocampal neurogenesis observed in AD may play a role. Adult-born neurons play a critical role in regulating both cognition and mood, and reduced hippocampal neurogenesis is associated with depression in other neurological disorders. To assess the relationship between Alzheimer's disease, neurogenesis, and depression, we studied human amyloid precursor protein (hAPP transgenic mice, a well-characterized model of AD. We report that reductions in hippocampal neurogenesis are evident early in disease progression in hAPP mice, but a mild depressive phenotype manifests only in later stages of disease. We found that hAPP mice exhibited a reduction in BrdU-positive cells in the subgranular zone of the dentate gyrus in the hippocampus, as well as a reduction in doublecortin-expressing cells, relative to nontransgenic controls at 5-7 months of age. These alterations in neurogenesis appeared to worsen with age, as the magnitude of reduction in doublecortin-expressing cells was greater in hAPP mice at 13-15 months of age. Only 13-15 month old hAPP mice exhibited depressive behavior in the tail suspension test. However, mice at both age groups exhibited deficits in spatial memory, which was observed in the Morris water maze test for hippocampus-dependent memory. These findings indicate that neurogenesis impairments are accompanied by cognitive deficits, but are not tightly linked to depressive behavior in hAPP mice.

  17. Temporal dynamics of hippocampal neurogenesis in chronic neurodegeneration

    Science.gov (United States)

    Suzzi, Stefano; Vargas-Caballero, Mariana; Fransen, Nina L.; Al-Malki, Hussain; Cebrian-Silla, Arantxa; Garcia-Verdugo, Jose Manuel; Riecken, Kristoffer; Fehse, Boris; Perry, V. Hugh

    2014-01-01

    The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms of the brain, and key to designing therapeutic strategies. In this study, using an experimental model of progressive chronic neurodegeneration, murine prion disease, we define the temporal dynamics of the generation, maturation and integration of new neurons in the hippocampal dentate gyrus, using dual pulse-chase, multicolour γ-retroviral tracing, transmission electron microscopy and patch-clamp. We found increased neurogenesis during the progression of prion disease, which partially counteracts the effects of chronic neurodegeneration, as evidenced by blocking neurogenesis with cytosine arabinoside, and helps to preserve the hippocampal function. Evidence obtained from human post-mortem samples, of both variant Creutzfeldt-Jakob disease and Alzheimer’s disease patients, also suggests increased neurogenic activity. These results open a new avenue into the exploration of the effects and regulation of neurogenesis during chronic neurodegeneration, and offer a new model to reproduce the changes observed in human neurodegenerative diseases. PMID:24941947

  18. Zinc and Neurogenesis: Making New Neurons from Development to Adulthood12

    OpenAIRE

    Levenson, Cathy W.; Morris, Deborah

    2011-01-01

    Stem cell proliferation, neuronal differentiation, cell survival, and migration in the central nervous system are all important steps in the normal process of neurogenesis. These mechanisms are highly active during gestational and early neonatal brain development. Additionally, in select regions of the brain, stem cells give rise to new neurons throughout the human lifespan. Recent work has revealed key roles for the essential trace element zinc in the control of both developmental and adult ...

  19. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice.

    Science.gov (United States)

    Yanai, Shogo; Hirano, Tetsushi; Omotehara, Takuya; Takada, Tadashi; Yoneda, Naoki; Kubota, Naoto; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2017-07-07

    Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life.

  20. Early postnatal weight gain as a predictor for the development of retinopathy of prematurity.

    Science.gov (United States)

    Biniwale, Manoj; Weiner, Angela; Sardesai, Smeeta; Cayabyab, Rowena; Barton, Lorayne; Ramanathan, Rangasamy

    2017-10-01

    The objective of this study is to validate the reliability of early postnatal weight gain as an accurate predictor of type 1 retinopathy of prematurity (ROP) requiring treatment in a large predominantly Hispanic US cohort with the use of an online tool called WINROP (weight, neonatal retinopathy of prematurity (IGF-1), neonatal retinopathy of prematurity). Retrospective cohort study consisted of preterm infants <32 weeks gestation and birth weight <1500 g. Weekly weights to 36 weeks post-menstrual age or discharge if earlier were entered into the WINROP tool. This tool generated alarm and risk indicator for developing ROP. The infants with type 1 ROP requiring treatment as well as all stages of ROP were compared with the alarms and risks generated by WINROP tool. A total of 492 infants were entered into the WINROP tool. The infants who developed type 1 ROP requiring treatment, the WINROP tool detected 80/89 (90%) at less than 32 weeks gestation. Nine infants developed type 1 ROP were classified as low risk and did not alarm. Postnatal weight gain alone, in predominantly Hispanic US population, predicted type 1 ROP requiring treatment before 32 weeks of gestation in infants with a sensitivity of 90%. The tool appeared to identify majority of affected infants much earlier than the scheduled screening.

  1. Impact of glucocorticoid on neurogenesis

    Directory of Open Access Journals (Sweden)

    Haruki Odaka

    2017-01-01

    Full Text Available Neurogenesis is currently an area of great interest in neuroscience. It is closely linked to brain diseases, including mental disorders and neurodevelopmental disease. Both embryonic and adult neurogeneses are influenced by glucocorticoids secreted from the adrenal glands in response to a variety of stressors. Moreover, proliferation/differentiation of the neural stem/progenitor cells (NSPCs is affected by glucocorticoids through intracellular signaling pathways such as phosphoinositide 3-kinase (PI3K/Akt, hedgehog, and Wnt. Our review presents recent evidence of the impact of glucocorticoids on NSPC behaviors and the underlying molecular mechanisms; this provides important information for understanding the pathological role of glucocorticoids on neurogenesis-associated brain diseases.

  2. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    Directory of Open Access Journals (Sweden)

    He Liu

    2016-01-01

    Full Text Available Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors.

  3. Adult Neurogenesis in Sheep: Characterization and Contribution to Reproduction and Behavior

    Science.gov (United States)

    Lévy, Frederic; Batailler, Martine; Meurisse, Maryse; Migaud, Martine

    2017-01-01

    Sheep have many advantages to study neurogenesis in comparison to the well-known rodent models. Their development and life expectancy are relatively long and they possess a gyrencephalic brain. Sheep are also seasonal breeders, a characteristic that allows studying the involvement of hypothalamic neurogenesis in the control of seasonal reproduction. Sheep are also able to individually recognize their conspecifics and develop selective and lasting bonds. Adult olfactory neurogenesis could be adapted to social behavior by supporting recognition of conspecifics. The present review reveals the distinctive features of the hippocampal, olfactory, and hypothalamic neurogenesis in sheep. In particular, the organization of the subventricular zone and the dynamic of neuronal maturation differs from that of rodents. In addition, we show that various physiological conditions, such as seasonal reproduction, gestation, and lactation differently modulate these three neurogenic niches. Last, we discuss recent evidence indicating that hypothalamic neurogenesis acts as an important regulator of the seasonal control of reproduction and that olfactory neurogenesis could be involved in odor processing in the context of maternal behavior. PMID:29109674

  4. Cognition and behavioural development in early childhood: the role of birth weight and postnatal growth.

    Science.gov (United States)

    Huang, Cheng; Martorell, Reynaldo; Ren, Aiguo; Li, Zhiwen

    2013-02-01

    We evaluate the relative importance of birth weight and postnatal growth for cognition and behavioural development in 8389 Chinese children, 4-7 years of age. Method Weight was the only size measure available at birth. Weight, height, head circumference and intelligence quotient (IQ) were measured between 4 and 7 years of age. Z-scores of birth weight and postnatal conditional weight gain to 4-7 years, as well as height and head circumference at 4-7 years of age, were the exposure variables. Z-scores of weight at 4-7 years were regressed on birth weight Z-scores, and the residual was used as the measure of postnatal conditional weight gain. The outcomes were child's IQ, measured by the Chinese Wechsler Young Children Scale of Intelligence, as well as internalizing behavioural problems, externalizing behavioural problems and other behavioural problems, evaluated by the Child Behavior Checklist 4-18. Multivariate regressions were conducted to investigate the relationship of birth weight and postnatal growth variables with the outcomes, separately for preterm children and term children. Both birth weight and postnatal weight gain were associated with IQ among term children; 1 unit increment in Z-score of birth weight (∼450 g) was associated with an increase of 1.60 [Confidence interval (CI): 1.18-2.02; P < 0.001] points in IQ, and 1 unit increment in conditional postnatal weight was associated with an increase of 0.46 (CI: 0.06-0.86; P = 0.02) points in IQ, after adjustment for confounders; similar patterns were observed when Z-scores of postnatal height and head circumference at age 4-7 years were used as alternative measurements of postnatal growth. Effect sizes of relationships with IQ were smaller than 0.1 of a standard deviation in all cases. Neither birth weight nor postnatal growth indicators were associated with behavioural outcomes among term children. In preterm children, neither birth weight nor postnatal growth measures were associated with IQ or

  5. Delayed growth, motor function and learning in preterm pigs during early postnatal life

    DEFF Research Database (Denmark)

    Andersen, Anders D.; Sangild, Per T.; Munch, Sara L.

    2016-01-01

    Preterm birth interrupts normal fetal growth with consequences for postnatal growth and organ development. In preterm infants, many physiological deficits adapt and disappear with advancing postnatal age, but some may persist into childhood. We hypothesized that preterm birth would induce impaired......, and learning, relative to term pigs (all P

  6. Early postnatal calcium and phosphorus metabolism in preterm infants

    NARCIS (Netherlands)

    Christmann, V.; Grauw, A.M. de; Visser, R.; Matthijsse, R.P.; Goudoever, J.B. van; Heijst, A.F.J. van

    2014-01-01

    OBJECTIVES: Bone mineralisation in preterm infants is related to the supply of calcium (Ca) and phosphorus (P). We increased the amount of minerals in parenteral nutrition (PN) for preterm infants and evaluated postnatal Ca and P metabolism in relation to mineral and vitamin D (vitD) intake.

  7. Adult Neurogenesis and Neurodegenerative Diseases: A Systems Biology Perspective

    Science.gov (United States)

    Horgusluoglu, Emrin; Nudelman, Kelly; Nho, Kwangsik; Saykin, Andrew J.

    2016-01-01

    New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research. PMID:26879907

  8. EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy

    Directory of Open Access Journals (Sweden)

    Mengtao Li

    2016-03-01

    Full Text Available Self-renewal and differentiation of neural stem cells is essential for embryonic neurogenesis, which is associated with cell autophagy. However, the mechanism by which autophagy regulates neurogenesis remains undefined. Here, we show that Eva1a/Tmem166, an autophagy-related gene, regulates neural stem cell self-renewal and differentiation. Eva1a depletion impaired the generation of newborn neurons, both in vivo and in vitro. Conversely, overexpression of EVA1A enhanced newborn neuron generation and maturation. Moreover, Eva1a depletion activated the PIK3CA-AKT axis, leading to the activation of the mammalian target of rapamycin and the subsequent inhibition of autophagy. Furthermore, addition of methylpyruvate to the culture during neural stem cell differentiation rescued the defective embryonic neurogenesis induced by Eva1a depletion, suggesting that energy availability is a significant factor in embryonic neurogenesis. Collectively, these data demonstrated that EVA1A regulates embryonic neurogenesis by modulating autophagy. Our results have potential implications for understanding the pathogenesis of neurodevelopmental disorders caused by autophagy dysregulation.

  9. Early postnatal calcium and phosphorus metabolism in preterm infants

    NARCIS (Netherlands)

    Christmann, Viola; de Grauw, Anne M.; Visser, Reina; Matthijsse, René P.; van Goudoever, Johannes B.; van Heijst, Arno F. J.

    2014-01-01

    Bone mineralisation in preterm infants is related to the supply of calcium (Ca) and phosphorus (P). We increased the amount of minerals in parenteral nutrition (PN) for preterm infants and evaluated postnatal Ca and P metabolism in relation to mineral and vitamin D (vitD) intake. Preterm infants,

  10. The early postnatal period: Exploring women's views, expectations and experiences of care using focus groups in Victoria, Australia

    Directory of Open Access Journals (Sweden)

    Rayner Jo

    2008-07-01

    Full Text Available Abstract Background There is growing evidence from Australia and overseas that the care provided in hospital in the early postnatal period is less than ideal for both women and care providers. Many health services face increasing pressure on hospital beds and have limited physical space available to care for mothers and their babies. We aimed to gain a more in-depth understanding of women's views, expectations and experiences of early postnatal care. Methods We conducted focus groups in rural and metropolitan Victoria, Australia in 2006. Fifty-two people participated in eight focus groups and four interviews. Participants included eight pregnant women, of whom seven were pregnant with their first baby; 42 women who were in the postpartum period (some up to twelve months after the birth of their baby; and two partners. All participants were fluent in English. Focus group guides were developed specifically for the study and explored participants' experiences and/or expectations of early postnatal care in hospital and at home, with an emphasis on length of hospital stay, professional and social support, continuity of care, and rest. Discussions were audio-taped and transcribed verbatim. A thematic network was constructed to describe and connect categories with emerging basic, organizing, and global themes. Results Global themes that emerged were: anxiety and/or fear; and the transition to motherhood and parenting. The needs of first time mothers were considered to be different to the needs of women who had already experienced motherhood. The women in this study were generally concerned about the safety of their new baby, and lacked confidence in themselves as new mothers regarding their ability to care for their baby. There was a consistent view that the physical presence and availability of professional support helped alleviate these concerns, and this was especially the case for women having a first baby. Conclusion Women have anxieties and fears

  11. Dentate Gyrus Neurogenesis, Integration, and microRNAs

    OpenAIRE

    Luikart, Bryan W; Perederiy, Julia V; Westbrook, Gary L

    2011-01-01

    Neurons are born and become a functional part of the synaptic circuitry in adult brains. The proliferative phase of neurogenesis has been extensively reviewed. We therefore focus this review on a few topics addressing the functional role of adult-generated newborn neurons in the dentate gyrus. We discuss the evidence for a link between neurogenesis and behavior. We then describe the steps in the integration of newborn neurons into a functioning mature synaptic circuit. Given the profound effe...

  12. Massage therapy during early postnatal life promotes greater lean mass and bone growth, mineralization, and strength in juvenile and young adult rats.

    Science.gov (United States)

    Chen, H; Miller, S; Shaw, J; Moyer-Mileur, L

    2009-01-01

    The objects of this study were to investigate the effects of massage therapy during early life on postnatal growth, body composition, and skeletal development in juvenile and young adult rats. Massage therapy was performed for 10 minutes daily from D6 to D10 of postnatal life in rat pups (MT, n=24). Body composition, bone area, mineral content, and bone mineral density were measured by dual energy X-ray absorptiometry (DXA); bone strength and intrinsic stiffness on femur shaft were tested by three-point bending; cortical and cancellous bone histomorphometric measurements were performed at D21 and D60. Results were compared to age- and gender-matched controls (C, n=24). D21 body weight, body length, lean mass, and bone area were significantly greater in the MT cohort. Greater bone mineral content was found in male MT rats; bone strength and intrinsic stiffness were greater in D60 MT groups. At D60 MT treatment promoted bone mineralization by increasing trabecular mineral apposition rate in male and endosteal mineral surface in females, and also improved micro-architecture by greater trabeculae width in males and decreasing trabecular separation in females. In summary, massage therapy during early life elicited immediate and prolonged anabolic effects on postnatal growth, lean mass and skeletal developmental in a gender-specific manner in juvenile and young adult rats.

  13. Divergent Roles of Central Serotonin in Adult Hippocampal Neurogenesis

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    Ning-Ning Song

    2017-06-01

    Full Text Available The central serotonin (5-HT system is the main target of selective serotonin reuptake inhibitors (SSRIs, the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we review how changes in the central serotonergic system alter adult hippocampal neurogenesis. We focus on data obtained from three categories of genetically engineered mouse models: (1 mice with altered central 5-HT levels from embryonic stages, (2 mice with deletion of 5-HT receptors from embryonic stages, and (3 mice with altered central 5-HT system exclusively in adulthood. These recent findings provide unique insights to interpret the multifaceted roles of central 5-HT on adult hippocampal neurogenesis and its associated effects on depression.

  14. Consequences of early postnatal benzodiazepines exposure in rats. I. Cognitive-like behavior

    Directory of Open Access Journals (Sweden)

    Anna eMikulecka

    2014-03-01

    Full Text Available Clinical and experimental studies suggest possible risks associated with the repeated administration of BZDS during the prenatal or early postnatal period on further development and behavior. In the present study, we assess short- and long-term effects of early exposure to clonazepam (CZP on cognitive tasks. CZP (0.5 or 1.0 mg/kg/day was administered from postnatal day (P7 until P11, and animals were exposed to the following behavioral tests at different developmental stages: (1 a homing response test, which exploits the motivation of a rat pup to reach its home nest, was administered on P12, P15, P18 and P23 rats; (2 passive avoidance was tested in three trials (at 0 h, 2 h and 24 h intervals on P12, P15, P18, P25 and P32 rats; (3 within- and between-session habituation was tested in an open field (OF at P70; and (4 a long-term memory version of the Morris water maze (MWM was tested at P80. A 1.0 mg/kg dose of CZP extended latency in the homing response and decreased the number of correct responses when tested at P12 and P23. In the first trial of the passive avoidance test, latency to enter a dark compartment was shorter in the CZP-exposed rats. Both treated and control animals older than P15 learned the passive-avoidance response at the same rate. Irrespective of the treatments, all adult animals showed within-session habituation. Between-session habituation, however, was found only in the controls. With respect to the MWM test, all animals learned to reach the platform, but animals exposed to higher doses of CZP spent more time swimming in the first acquisition test. No difference between groups was found in a repeated acquisition test (10 and 40 days after the first acquisition test. The results of the present study show that even short-term exposure to CZP alters behavioral responsiveness in pre-weaning, juvenile and adult animals. Not only were changes observed on conventional cognitive tests in our study, but the changes also seem to be

  15. SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory.

    Science.gov (United States)

    Chen, Qian; Kogan, Jeffrey H; Gross, Adam K; Zhou, Yuan; Walton, Noah M; Shin, Rick; Heusner, Carrie L; Miyake, Shinichi; Tajinda, Katsunori; Tamura, Kouichi; Matsumoto, Mitsuyuki

    2012-09-01

    SREB2/GPR85, a member of the super-conserved receptor expressed in brain (SREB) family, is the most conserved G-protein-coupled receptor in vertebrate evolution. Previous human and mouse genetic studies have indicated a possible link between SREB2 and schizophrenia. SREB2 is robustly expressed in the hippocampal formation, especially in the dentate gyrus, a structure with an established involvement in psychiatric disorders and cognition. However, the function of SREB2 in the hippocampus remains elusive. Here we show that SREB2 regulates hippocampal adult neurogenesis, which impacts on cognitive function. Bromodeoxyuridine incorporation and immunohistochemistry were conducted in SREB2 transgenic (Tg, over-expression) and knockout (KO, null-mutant) mice to quantitatively assay adult neurogenesis and newborn neuron dendritic morphology. Cognitive responses associated with adult neurogenesis alteration were evaluated in SREB2 mutant mice. In SREB2 Tg mice, both new cell proliferation and new neuron survival were decreased in the dentate gyrus, whereas an enhancement of new neuron survival occurred in SREB2 KO mouse dentate gyrus. Doublecortin staining revealed dendritic morphology deficits of newly generated neurons in SREB2 Tg mice. In a spatial pattern separation task, SREB2 Tg mice displayed a decreased ability to discriminate spatial relationships, whereas SREB2 KO mice had enhanced abilities in this task. Additionally, SREB2 Tg and KO mice had reciprocal phenotypes in a Y-maze working memory task. Our results indicate that SREB2 is a negative regulator of adult neurogenesis and consequential cognitive functions. Inhibition of SREB2 function may be a novel approach to enhance hippocampal adult neurogenesis and cognitive abilities to ameliorate core symptoms of psychiatric patients. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  16. Effect of prenatal and postnatal malnutrition on intellectual functioning in early school-aged children in rural western China

    OpenAIRE

    Li, Chao; Zhu, Ni; Zeng, Lingxia; Dang, Shaonong; Zhou, Jing; Yan, Hong

    2016-01-01

    Abstract The aim of this study was to evaluate the effect of prenatal and postnatal malnutrition on the intellectual functioning of early school-aged children. We followed the offspring of women who had participated in a trial of prenatal supplementation with different combinations of micronutrients and who remained resident in the study field. We measured their intellectual functioning using the Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for-age, and body mass...

  17. Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress.

    Science.gov (United States)

    Murphy, Margaret O; Herald, Joseph B; Wills, Caleb T; Unfried, Stanley G; Cohn, Dianne M; Loria, Analia S

    2017-02-01

    Experimental studies in rodents have shown that females are more susceptible to exhibiting fat expansion and metabolic disease compared with males in several models of fetal programming. This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2-14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no diet-induced differences in body weight (BW), glucose tolerance, and fat tissue weight and morphology were found between MatSep and control male rats. However, female MatSep rats displayed increased BW gain, fat pad weights, and glucose intolerance compared with control rats (P obesity risk factors, including elevated adiposity, hyperleptinemia, and glucose intolerance. These findings show that exposure to stress hormones during early life could be a key event to enhance diet-induced obesity and metabolic disease in female rats. Thus, pharmacological and/or behavioral inflection of the stress levels is a potential therapeutic approach for prevention of early life stress-enhanced obesity and metabolic disease. Copyright © 2017 the American Physiological Society.

  18. Adolescent Mouse Takes on An Active Transcriptomic Expression During Postnatal Cerebral Development

    KAUST Repository

    Xu, Wei

    2014-06-01

    Postnatal cerebral development is a complicated biological process precisely controlled by multiple genes. To understand the molecular mechanism of cerebral development, we compared dynamics of mouse cerebrum transcriptome through three developmental stages using high-throughput RNA-seq technique. Three libraries were generated from the mouse cerebrum at infancy, adolescence and adulthood, respectively. Consequently, 44,557,729 (infancy), 59,257,530 (adolescence) and 72,729,636 (adulthood) reads were produced, which were assembled into 15,344, 16,048 and 15,775 genes, respectively. We found that the overall gene expression level increased from infancy to adolescence and decreased later on upon reaching adulthood. The adolescence cerebrum has the most active gene expression, with expression of a large number of regulatory genes up-regulated and some crucial pathways activated. Transcription factor (TF) analysis suggested the similar dynamics as expression profiling, especially those TFs functioning in neurogenesis differentiation, oligodendrocyte lineage determination and circadian rhythm regulation. Moreover, our data revealed a drastic increase in myelin basic protein (MBP)-coding gene expression in adolescence and adulthood, suggesting that the brain myelin may be generated since mouse adolescence. In addition, differential gene expression analysis indicated the activation of rhythmic pathway, suggesting the function of rhythmic movement since adolescence; Furthermore, during infancy and adolescence periods, gene expression related to axon. repulsion and attraction showed the opposite trends, indicating that axon repulsion was activated after birth, while axon attraction might be activated at the embryonic stage and declined during the postnatal development. Our results from the present study may shed light on the molecular mechanism underlying the postnatal development of the mammalian cerebrum. © 2014 .

  19. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    Science.gov (United States)

    Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

    2017-04-01

    Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P controls and was associated with significantly reduced plasma levels of mouse GH ( P controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.

  20. Forebrain neurogenesis: From embryo to adult.

    Science.gov (United States)

    Dennis, Daniel; Picketts, David; Slack, Ruth S; Schuurmans, Carol

    2016-01-01

    A satellite symposium to the Canadian Developmental Biology Conference 2016 was held on March 16-17, 2016 in Banff, Alberta, Canada, entitled Forebrain Neurogenesis : From embryo to adult . The Forebrain Neurogenesis symposium was a focused, high-intensity meeting, bringing together the top Canadian and international researchers in the field. This symposium reported the latest breaking news, along with 'state of the art' techniques to answer fundamental questions in developmental neurobiology. Topics covered ranged from stem cell regulation to neurocircuitry development, culminating with a session focused on neuropsychiatric disorders. Understanding the underlying causes of neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) is of great interest as diagnoses of these conditions are climbing at alarming rates. For instance, in 2012, the Centers for Disease Control reported that the prevalence rate of ASD in the U.S. was 1 in 88; while more recent data indicate that the number is as high as 1 in 68 (Centers for Disease Control and Prevention MMWR Surveillance Summaries. Vol. 63. No. 2). Similarly, the incidence of ASD is on the rise in Canada, increasing from 1 in 150 in 2000 to 1 in 63 in 2012 in southeastern Ontario (Centers for Disease Control and Prevention). Currently very little is known regarding the deficits underlying these neurodevelopmental conditions. Moreover, the development of effective therapies is further limited by major gaps in our understanding of the fundamental processes that regulate forebrain development and adult neurogenesis. The Forebrain Neurogenesis satellite symposium was thus timely, and it played a key role in advancing research in this important field, while also fostering collaborations between international leaders, and inspiring young researchers.

  1. Nuclear deterrents: Intrinsic regulators of IL-1β-induced effects on hippocampal neurogenesis.

    Science.gov (United States)

    O'Léime, Ciarán S; Cryan, John F; Nolan, Yvonne M

    2017-11-01

    Hippocampal neurogenesis, the process by which new neurons are born and develop into the host circuitry, begins during embryonic development and persists throughout adulthood. Over the last decade considerable insights have been made into the role of hippocampal neurogenesis in cognitive function and the cellular mechanisms behind this process. Additionally, an increasing amount of evidence exists on the impact of environmental factors, such as stress and neuroinflammation on hippocampal neurogenesis and subsequent impairments in cognition. Elevated expression of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the hippocampus is established as a significant contributor to the neuronal demise evident in many neurological and psychiatric disorders and is now known to negatively regulate hippocampal neurogenesis. In order to prevent the deleterious effects of IL-1β on neurogenesis it is necessary to identify signalling pathways and regulators of neurogenesis within neural progenitor cells that can interact with IL-1β. Nuclear receptors are ligand regulated transcription factors that are involved in modulating a large number of cellular processes including neurogenesis. In this review we focus on the signalling mechanisms of specific nuclear receptors involved in regulating neurogenesis (glucocorticoid receptors, peroxisome proliferator activated receptors, estrogen receptors, and nuclear receptor subfamily 2 group E member 1 (NR2E1 or TLX)). We propose that these nuclear receptors could be targeted to inhibit neuroinflammatory signalling pathways associated with IL-1β. We discuss their potential to be therapeutic targets for neuroinflammatory disorders affecting hippocampal neurogenesis and associated cognitive function. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Early postnatal exposure to intermittent hypoxia in rodents is proinflammatory, impairs white matter integrity, and alters brain metabolism.

    Science.gov (United States)

    Darnall, Robert A; Chen, Xi; Nemani, Krishnamurthy V; Sirieix, Chrystelle M; Gimi, Barjor; Knoblach, Susan; McEntire, Betty L; Hunt, Carl E

    2017-07-01

    BackgroundPreterm infants are frequently exposed to intermittent hypoxia (IH) associated with apnea and periodic breathing that may result in inflammation and brain injury that later manifests as cognitive and executive function deficits. We used a rodent model to determine whether early postnatal exposure to IH would result in inflammation and brain injury.MethodsRat pups were exposed to IH from P2 to P12. Control animals were exposed to room air. Cytokines were analyzed in plasma and brain tissue at P13 and P18. At P20-P22, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were performed.ResultsPups exposed to IH had increased plasma Gro/CXCL1 and cerebellar IFN-γ and IL-1β at P13, and brainstem enolase at P18. DTI showed a decrease in FA and AD in the corpus callosum (CC) and cingulate gyrus, and an increase in RD in the CC. MRS revealed decreases in NAA/Cho, Cr, Tau/Cr, and Gly/Cr; increases in TCho and GPC in the brainstem; and decreases in NAA/Cho in the hippocampus.ConclusionsWe conclude that early postnatal exposure to IH, similar in magnitude to that experienced in human preterm infants, is associated with evidence for proinflammatory changes, decreases in white matter integrity, and metabolic changes consistent with hypoxia.

  3. Adult hippocampal neurogenesis: an important target associated with antidepressant effects of exercise.

    Science.gov (United States)

    Sun, Lina; Sun, Qingshan; Qi, Jinshun

    2017-10-26

    Depression is a prevalent devastating mental disorder that affects the normal life of patients and brings a heavy burden to whole society. Although many efforts have been made to attenuate depressive/anxiety symptoms, the current clinic antidepressants have limited effects. Scientists have long been making attempts to find some new strategies that can be applied as the alternative antidepressant therapy. Exercise, a widely recognized healthy lifestyle, has been suggested as a therapy that can relieve psychiatric stress. However, how exercise improves the brain functions and reaches the antidepressant target needs systematic summarization due to the complexity and heterogeneous feature of depression. Brain plasticity, especially adult neurogenesis in the hippocampus, is an important neurophysiology to facilitate animals for neurogenesis can occur in not only humans. Many studies indicated that an appropriate level of exercise can promote neurogenesis in the adult brains. In this article, we provide information about the antidepressant effects of exercise and its implications in adult neurogenesis. From the neurogenesis perspective, we summarize evidence about the effects of exercise in enhancing neurogenesis in the hippocampus through regulating growth factors, neurotrophins, neurotransmitters and metabolism as well as inflammations. Taken together, a large number of published works indicate the multiple benefits of exercise in the brain functions of animals, particularly brain plasticity like neurogenesis and synaptogenesis. Therefore, a new treatment method for depression therapy can be developed by regulating the exercise activity.

  4. Behaviour of postnatally growth-impaired mice during malnutrition and after partial weight recovery

    DEFF Research Database (Denmark)

    Huber, Reinhard C.; Kolb, Andreas F.; Lillico, Simon

    2013-01-01

    Objectives: Early malnutrition is a highly prevalent condition in developing countries. Different rodent models of postnatal early malnutrition have been used to approach the subject experimentally, inducing early malnutrition by maternal malnutrition, temporal maternal separation, manipulation...... of litter size or the surgical nipple ligation to impair lactation. Studies on the behaviour of (previously) malnourished animals using animal models have produced sometimes contradictory results regarding the effects of early postnatal malnutrition and have been criticized for introducing potential...... confounding factors. The present paper is a first report on the behavioural effects of early malnutrition induced by an alternative approach: mice nursed by a-casein-deficient knockout dams showed a severe growth delay during early development and substantial catch-up growth after weaning when compared...

  5. THE SOCIAL ENVIRONMENT AND NEUROGENESIS IN THE ADULT MAMMALIAN BRAIN

    Directory of Open Access Journals (Sweden)

    Claudia eLieberwirth

    2012-05-01

    Full Text Available Adult neurogenesis—the formation of new neurons in adulthood—has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones as well as exogenous (e.g., physical activity and environmental complexity factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. Most recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult-adult (e.g., mating, conspecific, and chemosensory signal exposure and adult-offspring (e.g., gestation, parenthood, and exposure to offspring interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant-subordinate interactions on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed.

  6. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life

    OpenAIRE

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P.; Klein, Jonathan D.; Chen, Gang; Lazarus, Philip; Collaco, Joseph M.; McGrath-Morrow, Sharon A.

    2015-01-01

    Nicotine exposure has been associated with an increased likelihood of developing attention deficit hyperactivity disorder (ADHD) in offspring of mothers who smoked during pregnancy. The goal of this study was to determine if exposure to E-cigarette nicotine vapors during late prenatal and early postnatal life altered behavior in adult mice. Methods: Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until d...

  7. APC/C-Cdh1 coordinates neurogenesis and cortical size during development

    Science.gov (United States)

    Delgado-Esteban, Maria; García-Higuera, Irene; Maestre, Carolina; Moreno, Sergio; Almeida, Angeles

    2013-12-01

    The morphology of the adult brain is the result of a delicate balance between neural progenitor proliferation and the initiation of neurogenesis in the embryonic period. Here we assessed whether the anaphase-promoting complex/cyclosome (APC/C) cofactor, Cdh1—which regulates mitosis exit and G1-phase length in dividing cells—regulates neurogenesis in vivo. We use an embryo-restricted Cdh1 knockout mouse model and show that functional APC/C-Cdh1 ubiquitin ligase activity is required for both terminal differentiation of cortical neurons in vitro and neurogenesis in vivo. Further, genetic ablation of Cdh1 impairs the ability of APC/C to promote neurogenesis by delaying the exit of the progenitor cells from the cell cycle. This causes replicative stress and p53-mediated apoptotic death resulting in decreased number of cortical neurons and cortex size. These results demonstrate that APC/C-Cdh1 coordinates cortical neurogenesis and size, thus posing Cdh1 in the molecular pathogenesis of congenital neurodevelopmental disorders, such as microcephaly.

  8. Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain.

    Directory of Open Access Journals (Sweden)

    Anke Popp

    Full Text Available BACKGROUND: GABA (gamma-aminobutyric acid, the main inhibitory neurotransmitter in the brain, is synthesized by glutamic acid decarboxylase (GAD. GAD exists in two adult isoforms, GAD65 and GAD67. During embryonic brain development at least two additional transcripts exist, I-80 and I-86, which are distinguished by insertions of 80 or 86 bp into GAD67 mRNA, respectively. Though it was described that embryonic GAD67 transcripts are not detectable during adulthood there are evidences suggesting re-expression under certain pathological conditions in the adult brain. In the present study we systematically analyzed for the first time the spatiotemporal distribution of different GADs with emphasis on embryonic GAD67 mRNAs in the postnatal brain using highly sensitive methods. METHODOLOGY/PRINCIPAL FINDINGS: QPCR was used to precisely investigate the postnatal expression level of GAD related mRNAs in cortex, hippocampus, cerebellum, and olfactory bulb of rats from P1 throughout adulthood. Within the first three postnatal weeks the expression of both GAD65 and GAD67 mRNAs reached adult levels in hippocampus, cortex, and cerebellum. The olfactory bulb showed by far the highest expression of GAD65 as well as GAD67 transcripts. Embryonic GAD67 splice variants were still detectable at birth. They continuously declined to barely detectable levels during postnatal development in all investigated regions with exception of a comparatively high expression in the olfactory bulb. Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream. CONCLUSIONS/SIGNIFICANCE: Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity. Therefore a functional role in processes like proliferation, migration or

  9. A flavonoid agonist of the TrkB receptor for BDNF improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn mouse model of DS.

    Science.gov (United States)

    Stagni, Fiorenza; Giacomini, Andrea; Guidi, Sandra; Emili, Marco; Uguagliati, Beatrice; Salvalai, Maria Elisa; Bortolotto, Valeria; Grilli, Mariagrazia; Rimondini, Roberto; Bartesaghi, Renata

    2017-12-01

    Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB). Systemic BDNF administration is impracticable because BDNF has a poor blood-brain barrier penetration. Recent screening of a chemical library has identified a flavone derivative, 7,8-dihydroxyflavone (7,8-DHF), a small-molecule that crosses the blood-brain barrier and binds with high affinity and specificity to the TrkB receptor. The therapeutic potential of TrkB agonists for neurogenesis improvement in DS has never been examined. The goal of our study was to establish whether it is possible to restore brain development in the Ts65Dn mouse model of DS by targeting the TrkB receptor with 7,8-DHF. Ts65Dn mice subcutaneously injected with 7,8-DHF in the neonatal period P3-P15 exhibited a large increase in the number of neural precursor cells in the dentate gyrus and restoration of granule cell number, density of dendritic spines and levels of the presynaptic protein synaptophysin. In order to establish the functional outcome of treatment, mice were treated with 7,8-DHF from P3 to adolescence (P45-50) and were tested with the Morris Water Maze. Treated Ts65Dn mice exhibited improvement of learning and memory, indicating that the recovery of the hippocampal anatomy translated into a functional rescue. Our study in a mouse model of DS provides novel evidence that treatment with 7,8-DHF during the early postnatal period restores the major trisomy-linked neurodevelopmental defects, suggesting that therapy with 7,8-DHF may represent a

  10. Sugar consumption produces effects similar to early life stress exposure on hippocampal markers of neurogenesis and stress response

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2016-01-01

    Full Text Available Adverse early life experience is a known risk factor for psychiatric disorders. It is also known that stress influences food preference. We were interested in exploring whether the choice of diet following early life stress exerts long-lasting molecular changes in the brain, particularly the hippocampus, a region critically involved in stress regulation and behavioural outcomes. Here, we examined the impact of early life stress induced by limited nesting material (LN and chronic sucrose availability post-weaning on an array of hippocampal genes related to plasticity, neurogenesis, stress and inflammatory responses and mitochondrial biogenesis. To examine mechanisms underlying the impact of LN and sugar intake on hippocampal gene expression, we investigated the role of DNA methylation. As females are more likely to experience adverse life events, we studied female Sprague-Dawley rats. After mating LN was imposed from days 2-9 postpartum. From 3-15 weeks of age, female Control and LN siblings had unlimited to access to either chow and water, or chow, water and 25% sucrose solution. LN markedly reduced glucocorticoid receptor (GR and neurogenic differentiation 1 (Neurod1 mRNA, markers involved in stress and hippocampal plasticity respectively, by more than 40%, with a similar effect of sugar intake in control rats. However, no further impact was observed in LN rats consuming sugar. Hippocampal Akt3 mRNA expression was similarly affected by LN and sucrose consumption. Interestingly, DNA methylation across 4 CpG sites of the GR and Neurod1 promoters was similar in LN and control rats. In summary, early life stress and post-weaning sugar intake produced long-term effects on hippocampal GR and Neurod1 expression. Moreover we found no evidence of altered promoter DNA methylation. We demonstrate for the first time that chronic sucrose consumption alone produces similar detrimental effects on the expression of hippocampal genes as LN exposure.

  11. A STEREOLOGICAL ANALYSIS OF THE EFFECT OF EARLY POSTNATAL ETHANOL EXPOSURE ON NEURONAL NUMBERS IN RAT DENTATE GYRUS

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    Takanori Miki

    2011-05-01

    Full Text Available Maternal ethanol ingestion during pregnancy can cause fetal alcohol syndrome (FAS in their offspring. Among the symptoms of FAS, damage to the central nervous system has emerged as one of the most serious problems. We have previously shown that a relatively high dose of ethanol exposure during early postnatal life can cause alterations in spatial learning ability. This ability is controlled, at least in part, by the hippocampal formation. The purpose of the present study was to determine whether exposure of rat pups to ethanol during early postnatal life had effects on the total number of the dentate gyrus neurons. Wistar rats were exposed to a relatively high daily dose of ethanol between postnatal days 10 to 15. Ethanol exposure was achieved by placing rat pups in a chamber containing ethanol vapour for 3 hours a day. The blood ethanol concentration was found to be about 430 mg/dL at the end of the exposure period. Groups of ethanol treated (ET, separation controls (SC and mother reared controls (MRC were anaesthetised and killed at 16-days-of-age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle was used to determine the volume of subdivisions of the dentate gyrus, and the physical disector method was used to estimate the numerical densities of neurons within each subdivision. The total number of neurons was calculated by multiplying estimates of the numerical density with the volume. There was, on average, about 421,000 granule cells in all three treatment groups. In the hilus region, ET rats had about 27,000 neuronal cells. This value was significantly smaller than the average of 38,000 such neurons estimated to be present in both MRC and SC animals. It is concluded that neurons in the hilus region of the dentate gyrus may be particularly vulnerable to the effects of a high dose of ethanol exposure during PND 10-15. It is likely that this deficit was due to neuronal death induced by some mechanisms related to

  12. Adolescent social isolation stress unmasks the combined effects of adolescent exercise and adult inflammation on hippocampal neurogenesis and behavior.

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    Hueston, Cara M; Cryan, John F; Nolan, Yvonne M

    2017-12-04

    Hippocampal neurogenesis and associated cognitive behaviors are regulated by a number of factors including stress, inflammation, and exercise. However, the interplay between these factors remains relatively unexplored, especially across the lifespan. In the current study, the effect of social isolation stress during the adolescent period on neurogenesis and hippocampal-dependent cognitive behaviors was examined. This period of the lifespan has been demonstrated to be an important time for hippocampal growth and plasticity, during which changes to hippocampal neurogenesis may have long lasting effects. Additionally, we aimed to determine whether a 'dual-hit' of adolescent stress and adult chronic neuroinflammation would potentiate any negative effects of either insult alone. Lastly, the potential positive effects of exercise during adolescence was examined to determine whether exercise could attenuate any negative impacts of these insults on hippocampal neurogenesis and behavior. The results from the current study demonstrate that social isolation stress during adolescence followed by intra-hippocampal exposure to the pro-inflammatory cytokine IL-1β in early adulthood produces deficits in both spontaneous alternations and novel object recognition. Exercise attenuated deficits in neurogenesis and novel object recognition in mice that had been exposed to the 'dual-hit' of stress and neuroinflammation. These findings indicate that adolescence represents a key period of the lifespan during which external factors such as stress and exercise can impact on hippocampal development, and may alter the response to challenges such as neuroinflammation in later life. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Tau protein and adult hippocampal neurogenesis

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    Almudena eFuster-Matanzo

    2012-07-01

    Full Text Available Tau protein is a microtubule associated protein found in the axonal compartment that stabilizes neuronal microtubules under normal physiological conditions. Tau metabolism has attracted much attention because of its role in neurodegenerative disorders called tauopathies, mainly Alzheimer disease. Here, we review recent findings suggesting that axonal outgrowth in subgranular zone during adult hippocampal neurogenesis requires a dynamic microtubule network and tau protein facilitates to maintain that dynamic cytoskeleton. Those functions are carried out in part by tau isoform with only three microtubule-binding domains (without exon 10 and by presence of hypherphosphorylated tau forms. Thus, tau is a good marker and a valuable tool to study new axons in adult neurogenesis.

  14. Maternal anxiety, risk factors and parenting in the first post-natal year.

    Science.gov (United States)

    Seymour, M; Giallo, R; Cooklin, A; Dunning, M

    2015-03-01

    The antecedents and consequences of maternal post-natal anxiety have received comparatively less attention than depression despite being one of the most frequently reported mental health difficulties experienced by parents following childbirth. The aim of this study was to extend emerging literature on post-natal anxiety by investigating the prevalence of maternal anxiety symptoms, and its relationship with parenting behaviours (i.e. warmth, hostility) and experiences (i.e. parenting efficacy and satisfaction) within the first post-natal year. The psychosocial risk factors for post-natal anxiety symptoms were also explored. A community sample of 224 Australian mothers of infants (aged 0-12 months) completed a self-report questionnaire. Mothers in the current sample reported significantly more symptoms of anxiety compared with a normative sample. Approximately 18% of mothers reported mild to extremely severe symptoms of anxiety, with a high proportion experiencing co-morbid depressive symptoms. Maternal anxiety was associated with low parenting warmth, involvement, efficacy and satisfaction, and high parenting hostility. Yet, co-morbid depression and anxiety was more strongly associated with these parenting behaviours and experiences than anxiety alone. A range of psychosocial risk factors (e.g. education, sleep, relationship quality) were associated with maternal post-natal anxiety symptoms, providing opportunities for early identification and targeted early intervention. © 2014 John Wiley & Sons Ltd.

  15. Spreading depression and focal venous cerebral ischemia enhance cortical neurogenesis

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    Ryo Tamaki

    2017-01-01

    Full Text Available Endogenous neurogenesis can arise from a variety of physiological stimuli including exercise, learning, or “enriched environment” as well as pathological conditions such as ischemia, epilepsy or cortical spreading depression. Whether all these conditions use a common trigger to set off endogenous neurogenesis is yet unclear. We hypothesized that cortical spreading depression (CSD induces neurogenesis in the cerebral cortex and dentate gyrus after cerebral venous ischemia. Forty-two Wistar rats alternatively underwent sham operation (Sham, induction of ten CSDs or venous ischemia provoked via occlusion of two adjacent superficial cortical vein followed by ten induced CSDs (CSD + 2-VO. As an additional control, 15 naïve rats received no intervention except 5-bromo-2′-deoxyuridine (BrdU treatment for 7 days. Sagittal brain slices (40 μm thick were co-stained for BrdU and doublecortin (DCX; new immature neuronal cells on day 9 or NeuN (new mature neuronal cells on day 28. On day 9 after sham operation, cell proliferation and neurogenesis occurred in the cortex in rats. The sole induction of CSD had no effect. But on days 9 and 28, more proliferating cells and newly formed neurons in the ipsilateral cortex were observed in rats subjected to CSD + 2VO than in rats subjected to sham operation. On days 9 and 28, cell proliferation and neurogenesis in the ipsilateral dentate gyrus was increased in sham-operated rats than in naïve rats. Our data supports the hypothesis that induced cortical neurogenesis after CSD + 2-VO is a direct effect of ischemia, rather than of CSD alone.

  16. Evaluation of the Adult Goldfish Brain as a Model for the Study of Progenitor Cells

    Science.gov (United States)

    2007-08-27

    embryo [34]. ESCs are able to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm, and they are...postnatal brain is their functional and anatomical destiny . Based on many reports investigating neurogenesis, the majority of newly produced cells...Homeodomain-bearing transcriptional factor. Expression is specific to early embryos and pluripotential stem cells. Key molecule involved in the

  17. The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis.

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    Stephen N Sansom

    2009-06-01

    Full Text Available Neural stem cell self-renewal, neurogenesis, and cell fate determination are processes that control the generation of specific classes of neurons at the correct place and time. The transcription factor Pax6 is essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central nervous system, including the cerebral cortex. We used Pax6 as an entry point to define the cellular networks controlling neural stem cell self-renewal and neurogenesis in stem cells of the developing mouse cerebral cortex. We identified the genomic binding locations of Pax6 in neocortical stem cells during normal development and ascertained the functional significance of genes that we found to be regulated by Pax6, finding that Pax6 positively and directly regulates cohorts of genes that promote neural stem cell self-renewal, basal progenitor cell genesis, and neurogenesis. Notably, we defined a core network regulating neocortical stem cell decision-making in which Pax6 interacts with three other regulators of neurogenesis, Neurog2, Ascl1, and Hes1. Analyses of the biological function of Pax6 in neural stem cells through phenotypic analyses of Pax6 gain- and loss-of-function mutant cortices demonstrated that the Pax6-regulated networks operating in neural stem cells are highly dosage sensitive. Increasing Pax6 levels drives the system towards neurogenesis and basal progenitor cell genesis by increasing expression of a cohort of basal progenitor cell determinants, including the key transcription factor Eomes/Tbr2, and thus towards neurogenesis at the expense of self-renewal. Removing Pax6 reduces cortical stem cell self-renewal by decreasing expression of key cell cycle regulators, resulting in excess early neurogenesis. We find that the relative levels of Pax6, Hes1, and Neurog2 are key determinants of a dynamic network that controls whether neural stem cells self-renew, generate cortical neurons, or generate basal progenitor cells

  18. Sonic hedgehog signaling regulates amygdalar neurogenesis and extinction of fear memory.

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    Hung, Hui-Chi; Hsiao, Ya-Hsin; Gean, Po-Wu

    2015-10-01

    It is now recognized that neurogenesis occurs throughout life predominantly in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricle. In the present study, we investigated the relationship between neurogenesis in the amygdala and extinction of fear memory. Mice received 15 tone-footshock pairings. Twenty-four hours after training, the mice were given 15 tone-alone trials (extinction training) once per day for 7 days. Two hours before extinction training, the mice were injected intraperitoneally with 5-bromo-3-deoxyuridine (BrdU). BrdU-positive and NeuN-positive cells were analyzed 52 days after the training. A group of mice that received tone-footshock pairings but no extinction training served as controls (FC+No-Ext). The number of BrdU(+)/NeuN(+) cells was significantly higher in the extinction (FC+Ext) than in the FC+No-Ext mice. Proliferation inhibitor methylazoxymethanol acetate (MAM) or DNA synthesis inhibitor cytosine arabinoside (Ara-C) reduced neurogenesis and retarded extinction. Silencing Sonic hedgehog (Shh) gene with short hairpin interfering RNA (shRNA) by means of a retrovirus expression system to knockdown Shh specifically in the mitotic neurons reduced neurogenesis and retarded extinction. By contrast, over-expression of Shh increased neurogenesis and facilitated extinction. These results suggest that amygdala neurogenesis and Shh signaling are involved in the extinction of fear memory. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  19. Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior.

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    Sun, Dong; Sun, Xiang-Dong; Zhao, Lu; Lee, Dae-Hoon; Hu, Jin-Xia; Tang, Fu-Lei; Pan, Jin-Xiu; Mei, Lin; Zhu, Xiao-Juan; Xiong, Wen-Cheng

    2018-01-08

    Adult neurogenesis in hippocampal dentate gyrus (DG) is a complex, but precisely controlled process. Dysregulation of this event contributes to multiple neurological disorders, including major depression. Thus, it is of considerable interest to investigate how adult hippocampal neurogenesis is regulated. Here, we present evidence for neogenin, a multifunctional transmembrane receptor, to regulate adult mouse hippocampal neurogenesis. Loss of neogenin in adult neural stem cells (NSCs) or neural progenitor cells (NPCs) impaired NSCs/NPCs proliferation and neurogenesis, whereas increased their astrocytic differentiation. Mechanistic studies revealed a role for neogenin to positively regulate Gli1, a crucial downstream transcriptional factor of sonic hedgehog, and expression of Gli1 into neogenin depleted NSCs/NPCs restores their proliferation. Further morphological and functional studies showed additional abnormities, including reduced dendritic branches and spines, and impaired glutamatergic neuro-transmission, in neogenin-depleted new-born DG neurons; and mice with depletion of neogenin in NSCs/NPCs exhibited depressive-like behavior. These results thus demonstrate unrecognized functions of neogenin in adult hippocampal NSCs/NPCs-promoting NSCs/NPCs proliferation and neurogenesis and preventing astrogliogenesis and depressive-like behavior, and suggest neogenin regulation of Gli1 signaling as a possible underlying mechanism.

  20. Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis.

    Science.gov (United States)

    Pérez-García, Georgina; Guzmán-Quevedo, Omar; Da Silva Aragão, Raquel; Bolaños-Jiménez, Francisco

    2016-02-17

    Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition.

  1. Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice.

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    Anna Fiorentini

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions, extracellular β-amyloid (Aβ plaques and intracellular neurofibrillary tangles within neocortex and hippocampus. Adult hippocampal neurogenesis plays an important role in learning and memory processes and its abnormal regulation might account for cognitive impairments associated with AD. METHODOLOGY/PRINCIPAL FINDINGS: The double transgenic (Tg CRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein, aged 2 and 6 months, were used to examine in vivo the effects of 5 weeks lithium treatment. BrdU labelling showed a decreased neurogenesis in the subgranular zone of Tg mice compared to non-Tg mice. The decrease of hippocampal neurogenesis was accompanied by behavioural deficits and worsened with age and pathology severity. The differentiation into neurons and maturation of the proliferating cells were also markedly impaired in the Tg mice. Lithium treatment to 2-month-old Tg mice significantly stimulated the proliferation and neuron fate specification of newborn cells and fully counteracted the transgene-induced impairments of cognitive functions. The drug, by the inhibition of GSK-3β and subsequent activation of Wnt/ß-catenin signalling promoted hippocampal neurogenesis. Finally, the data show that the lithium's ability to stimulate neurogenesis and cognitive functions was lost in the aged Tg mice, thus indicating that the lithium-induced facilitation of neurogenesis and cognitive functions declines as brain Aβ deposition and pathology increases. CONCLUSIONS: Lithium, when given on time, stimulates neurogenesis and counteracts AD-like pathology.

  2. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

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    Oosthuizen, M K; Amrein, I

    2016-06-02

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Influence of prenatal and postnatal growth on intellectual functioning in school-aged children.

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    Pongcharoen, Tippawan; Ramakrishnan, Usha; DiGirolamo, Ann M; Winichagoon, Pattanee; Flores, Rafael; Singkhornard, Jintana; Martorell, Reynaldo

    2012-05-01

    To assess the relative influence of size at birth, infant growth, and late postnatal growth on intellectual functioning at 9 years of age. A follow-up, cross-sectional study. Three districts in Khon Kaen province, northeast Thailand. A total of 560 children, or 92% of former participants of a trial of iron and/or zinc supplementation during infancy. Prenatal (size at birth), early infancy (birth to 4 months), late infancy (4 months to 1 year), and late postnatal (1 to 9 years) growth. Multiple-stage least squares analyses were used to generate uncorrelated residuals of postnatal growth. Intellectual functioning was measured at 9 years using the Wechsler Intelligence Scale for Children and the Raven's Colored Progressive Matrices (Pearson). Analyses included adjustment for maternal, household, and school characteristics. Significant relationships were found between growth and IQ (Wechsler Intelligence Scale for children, third edition, Thai version), but only up to 1 year of age; overall, growth was not related to the Raven's Colored Progressive Matrices. The strongest and most consistent relationships were with length (birth, early infancy, and late infancy); for weight, only early infancy gain was consistently related to IQ. Head circumference at birth was not collected routinely; head circumference at 4 months (but not head circumference growth thereafter) was related to IQ. Late postnatal growth was not associated with any outcome. Physical growth in early infancy (and, to a lesser extent, physical growth in late infancy and at birth) is associated with IQ at 9 years of age. Early infancy may be a critical window for human development.

  4. Neurogenesis and brain injury: managing a renewable resource for repair

    OpenAIRE

    Hallbergson, Anna F.; Gnatenco, Carmen; Peterson, Daniel A.

    2003-01-01

    The brain shows limited ability to repair itself, but neurogenesis in certain areas of the adult brain suggests that neural stem cells may be used for structural brain repair. It will be necessary to understand how neurogenesis in the adult brain is regulated to develop strategies that harness neural stem cells for therapeutic use.

  5. Deletion of TLX and social isolation impairs exercise-induced neurogenesis in the adolescent hippocampus.

    Science.gov (United States)

    Kozareva, Danka A; O'Leary, Olivia F; Cryan, John F; Nolan, Yvonne M

    2018-01-01

    Adolescence is a sensitive period of neurodevelopment during which life experiences can have profound effects on the brain. Hippocampal neurogenesis, the neurodevelopmental process of generating functional new neurons from neural stem cells, occurs throughout the lifespan and has been shown to play a role in learning, memory and in mood regulation. In adulthood it is influenced by extrinsic environmental factors such as exercise and stress. Intrinsic factors that regulate hippocampal neurogenesis include the orphan nuclear receptor TLX (Nr2e1) which is primarily expressed in the neurogenic niches of the brain. While mechanisms regulating adult hippocampal neurogenesis have been widely studied, less is known on how hippocampal neurogenesis is affected during adolescence. The aim of this study was to investigate the influence of both TLX and isolation stress on exercise-induced increases in neurogenesis in running and sedentary conditions during adolescence. Single- (isolation stress) wild type and Nr2e1 -/- mice or pair-housed wild type mice were housed in sedentary conditions or allowed free access to running wheels for 3 weeks during adolescence. A reduction of neuronal survival was evident in mice lacking TLX, and exercise did not increase hippocampal neurogenesis in these Nr2e1 -/- mice. This suggests that TLX is necessary for the pro-neurogenic effects of exercise during adolescence. Interestingly, although social isolation during adolescence did not affect hippocampal neurogenesis, it prevented an exercise-induced increase in neurogenesis in the ventral hippocampus. Together these data demonstrate the importance of intrinsic and extrinsic factors in promoting an exercise-induced increase in neurogenesis at this key point in life. © 2017 Wiley Periodicals, Inc.

  6. Neurogenesis in the aging brain.

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    Apple, Deana M; Solano-Fonseca, Rene; Kokovay, Erzsebet

    2017-10-01

    Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair. In this review, we describe NSCs and their niches during tissue homeostasis and how they undergo age-associated remodeling and dysfunction. We also discuss some of the functional ramifications in the brain from NSC aging. Finally, we discuss some recent insights from interventions in NSC aging that could eventually translate into therapies for healthy brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Fetal Nicotine Exposure Increases Preference for Nicotine Odor in Early Postnatal and Adolescent, but Not Adult, Rats

    Science.gov (United States)

    Mantella, Nicole M.; Kent, Paul F.; Youngentob, Steven L.

    2013-01-01

    Human studies demonstrate a four-fold increased possibility of smoking in the children of mothers who smoked during pregnancy. Nicotine is the active addictive component in tobacco-related products, crossing the placenta and contaminating the amniotic fluid. It is known that chemosensory experience in the womb can influence postnatal odor-guided preference behaviors for an exposure stimulus. By means of behavioral and neurophysiologic approaches, we examined whether fetal nicotine exposure, using mini-osmotic pumps, altered the response to nicotine odor in early postnatal (P17), adolescent (P35) and adult (P90) progeny. Compared with controls, fetal exposed rats displayed an altered innate response to nicotine odor that was evident at P17, declined in magnitude by P35 and was absent at P90 - these effects were specific to nicotine odor. The behavioral effect in P17 rats occurred in conjunction with a tuned olfactory mucosal response to nicotine odor along with an untoward consequence on the epithelial response to other stimuli – these P17 neural effects were absent in P35 and P90 animals. The absence of an altered neural effect at P35 suggests that central mechanisms, such as nicotine-induced modifications of the olfactory bulb, bring about the altered behavioral response to nicotine odor. Together, these findings provide insights into how fetal nicotine exposure influences the behavioral preference and responsiveness to the drug later in life. Moreover, they add to a growing literature demonstrating chemosensory mechanisms by which patterns of maternal drug use can be conveyed to offspring, thereby enhancing postnatal vulnerability for subsequent use and abuse. PMID:24358374

  8. Linking adult hippocampal neurogenesis with human physiology and disease.

    Science.gov (United States)

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions

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    Ming, Guo-li; Song, Hongjun

    2011-01-01

    Summary Adult neurogenesis, a process of generating functional neurons from adult neural precursors, occurs throughout life in restricted brain regions in mammals. The past decade has witnessed tremendous progress in addressing questions related to almost every aspect of adult neurogenesis in the mammalian brain. Here we review major advances in our understanding of adult mammalian neurogenesis in the dentate gyrus of the hippocampus and from the subventricular zone of the lateral ventricle, the rostral migratory stream to the olfactory bulb. We highlight emerging principles that have significant implications for stem cell biology, developmental neurobiology, neural plasticity, and disease mechanisms. We also discuss remaining questions related to adult neural stem cells and their niches, underlying regulatory mechanisms and potential functions of newborn neurons in the adult brain. Building upon the recent progress and aided by new technologies, the adult neurogenesis field is poised to leap forward in the next decade. PMID:21609825

  10. BMP signaling mediates effects of exercise on hippocampal neurogenesis and cognition in mice.

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    Kevin T Gobeske

    2009-10-01

    Full Text Available Exposure to exercise or to environmental enrichment increases the generation of new neurons in the adult hippocampus and promotes certain kinds of learning and memory. While the precise role of neurogenesis in cognition has been debated intensely, comparatively few studies have addressed the mechanisms linking environmental exposures to cellular and behavioral outcomes. Here we show that bone morphogenetic protein (BMP signaling mediates the effects of exercise on neurogenesis and cognition in the adult hippocampus. Elective exercise reduces levels of hippocampal BMP signaling before and during its promotion of neurogenesis and learning. Transgenic mice with decreased BMP signaling or wild type mice infused with a BMP inhibitor both exhibit remarkable gains in hippocampal cognitive performance and neurogenesis, mirroring the effects of exercise. Conversely, transgenic mice with increased BMP signaling have diminished hippocampal neurogenesis and impaired cognition. Exercise exposure does not rescue these deficits, suggesting that reduced BMP signaling is required for environmental effects on neurogenesis and learning. Together, these observations show that BMP signaling is a fundamental mechanism linking environmental exposure with changes in cognitive function and cellular properties in the hippocampus.

  11. [Postnatal diagnosis of gastric volvulus revealing congenital diaphragmatic hernia].

    Science.gov (United States)

    Aprahamian, A; Nouyrigat, V; Grévent, D; Hervieux, E; Chéron, G

    2017-05-01

    Postnatally diagnosed congenital diaphragmatic hernias (CDH) are rare and have a better prognosis than those diagnosed prenatally. Postnatal symptoms can be respiratory, digestive, or mixed. Gastric volvulus can reveal CDH. Symptoms are pain, abdominal distension, and/or vomiting. Upper gastrointestinal barium X-ray radiography provides the diagnosis. Prognosis is related to early surgical management in complicated forms with intestinal occlusion or sub-occlusion. We report on an infant who presented with vomiting, which revealed gastric volvulus associated with a CDH. Progression was favorable after surgical treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Developmental programming of somatic growth, behavior and endocannabinoid metabolism by variation of early postnatal nutrition in a cross-fostering mouse model.

    Science.gov (United States)

    Schreiner, Felix; Ackermann, Merle; Michalik, Michael; Hucklenbruch-Rother, Eva; Bilkei-Gorzo, Andras; Racz, Ildiko; Bindila, Laura; Lutz, Beat; Dötsch, Jörg; Zimmer, Andreas; Woelfle, Joachim

    2017-01-01

    Nutrient deprivation during early development has been associated with the predisposition to metabolic disorders in adulthood. Considering its interaction with metabolism, appetite and behavior, the endocannabinoid (eCB) system represents a promising target of developmental programming. By cross-fostering and variation of litter size, early postnatal nutrition of CB6F1-hybrid mice was controlled during the lactation period (3, 6, or 10 pups/mother). After weaning and redistribution at P21, all pups received standard chow ad libitum. Gene expression analyses (liver, visceral fat, hypothalamus) were performed at P50, eCB concentrations were determined in liver and visceral fat. Locomotor activity and social behavior were analyzed by means of computer-assisted videotracking. Body growth was permanently altered, with differences for length, weight, body mass index and fat mass persisting beyond P100 (all 3>6>10,p6>10 (DAGLα p6>10 (FAAH pOpen-field social behavior testing revealed significant group differences, with formerly underfed mice turning out to be the most sociable animals (p<0.01). Locomotor activity did not differ. Our data indicate a developmental plasticity of somatic growth, behavior and parameters of the eCB system, with long-lasting impact of early postnatal nutrition. Developmental programming of the eCB system in metabolically active tissues, as shown here for liver and fat, may play a role in the formation of the adult cardiometabolic risk profile following perinatal malnutrition in humans.

  13. Comparative aspects of adult neural stem cell activity in vertebrates.

    Science.gov (United States)

    Grandel, Heiner; Brand, Michael

    2013-03-01

    At birth or after hatching from the egg, vertebrate brains still contain neural stem cells which reside in specialized niches. In some cases, these stem cells are deployed for further postnatal development of parts of the brain until the final structure is reached. In other cases, postnatal neurogenesis continues as constitutive neurogenesis into adulthood leading to a net increase of the number of neurons with age. Yet, in other cases, stem cells fuel neuronal turnover. An example is protracted development of the cerebellar granular layer in mammals and birds, where neurogenesis continues for a few weeks postnatally until the granular layer has reached its definitive size and stem cells are used up. Cerebellar growth also provides an example of continued neurogenesis during adulthood in teleosts. Again, it is the granular layer that grows as neurogenesis continues and no definite adult cerebellar size is reached. Neuronal turnover is most clearly seen in the telencephalon of male canaries, where projection neurons are replaced in nucleus high vocal centre each year before the start of a new mating season--circuitry reconstruction to achieve changes of the song repertoire in these birds? In this review, we describe these and other examples of adult neurogenesis in different vertebrate taxa. We also compare the structure of the stem cell niches to find common themes in their organization despite different functions adult neurogenesis serves in different species. Finally, we report on regeneration of the zebrafish telencephalon after injury to highlight similarities and differences of constitutive neurogenesis and neuronal regeneration.

  14. A Common Language: How Neuroimmunological Cross Talk Regulates Adult Hippocampal Neurogenesis

    Directory of Open Access Journals (Sweden)

    Odette Leiter

    2016-01-01

    Full Text Available Immune regulation of the brain is generally studied in the context of injury or disease. Less is known about how the immune system regulates the brain during normal brain function. Recent work has redefined the field of neuroimmunology and, as long as their recruitment and activation are well regulated, immune cells are now known to have protective properties within the central nervous system in maintaining brain health. Adult neurogenesis, the process of new neuron generation in the adult brain, is highly plastic and regulated by diverse extrinsic and intrinsic cues. Emerging research has shown that immune cells and their secreted factors can influence adult neurogenesis, both under baseline conditions and during conditions known to change neurogenesis levels, such as aging and learning in an enriched environment. This review will discuss how, under nonpathological conditions, the immune system can interact with the neural stem cells to regulate adult neurogenesis with particular focus on the hippocampus—a region crucial for learning and memory.

  15. Elevated homocysteine by levodopa is detrimental to neurogenesis in parkinsonian model.

    Directory of Open Access Journals (Sweden)

    Jin Young Shin

    Full Text Available BACKGROUND: Modulation of neurogenesis that acts as an endogenous repair mechanism would have a significant impact on future therapeutic strategies for Parkinson's disease (PD. Several studies demonstrated dopaminergic modulation of neurogenesis in the subventricular zone (SVZ of the adult brain. Levodopa, the gold standard therapy for PD, causes an increase in homocysteine levels that induces neuronal death via N-methyl-D-aspartate (NMDA receptor. The present study investigated whether elevated homocysteine by levodopa treatment in a parkinsonian model would modulate neurogenesis via NMDA receptor signal cascade and compared the effect of levodopa and pramipexol (PPX on neurogenic activity. METHODOLOGY/PRINCIPAL FINDINGS: Neurogenesis was assessed in vitro using neural progenitor cells (NPCs isolated from the SVZ and in vivo with the BrdU-injected animal model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Modulation of homocysteine levels was evaluated using co-cultures of NPCs and astrocytes and PD animals. Immunochemical and Western blot analyses were used to measure neurogenesis and determine the cell death signaling. Levodopa treatment increased release of homocysteine on astrocytes culture media as well as in plasma and brain of PD animals. Increased homocysteine by levodopa led to increased apoptosis of NPCs through the NMDA receptor-dependent the extracellular signal-regulated kinase (ERK signaling pathways. The administration of a NMDA antagonist significantly attenuated apoptotic cell death in levodopa-treated NPCs and markedly increased the number of BrdU-positive cells in the SVZ of levodopa-treated PD animals. Comparative analysis revealed that PPX treatment significantly increased the number of NPCs and BrdU-positive cells in the SVZ of PD animals compared to levodopa treatment. Our present study demonstrated that increased homocysteine by levodopa has a detrimental effect on neurogenesis through NMDA receptor

  16. Doc Title: Adult Hippocampal Neurogenesis is Impaired by Transient Developmental Thyroid Hormone Disruption

    Data.gov (United States)

    U.S. Environmental Protection Agency — Severe thyroid hormone (TH) deprivation during development impairs neurogenesis throughout the brain. The hippocampus also maintains a capacity for neurogenesis...

  17. Pre- and Post-Natal Maternal Depressive Symptoms in Relation with Infant Frontal Function, Connectivity, and Behaviors

    Science.gov (United States)

    Soe, Ni Ni; Wen, Daniel J.; Poh, Joann S.; Li, Yue; Broekman, Birit F. P.; Chen, Helen; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D.; Meaney, Michael J.; Rifkin-Graboi, Anne; Qiu, Anqi

    2016-01-01

    This study investigated the relationships between pre- and early post-natal maternal depression and their changes with frontal electroencephalogram (EEG) activity and functional connectivity in 6- and 18-month olds, as well as externalizing and internalizing behaviors in 24-month olds (n = 258). Neither prenatal nor postnatal maternal depressive symptoms independently predicted neither the frontal EEG activity nor functional connectivity in 6- and 18-month infants. However, increasing maternal depressive symptoms from the prenatal to postnatal period predicted greater right frontal activity and relative right frontal asymmetry amongst 6-month infants but these finding were not observed amongst 18-month infants after adjusted for post-conceptual age on the EEG visit day. Subsequently increasing maternal depressive symptoms from the prenatal to postnatal period predicted lower right frontal connectivity within 18-month infants but not among 6-month infants after controlling for post-conceptual age on the EEG visit day. These findings were observed in the full sample and the female sample but not in the male sample. Moreover, both prenatal and early postnatal maternal depressive symptoms independently predicted children’s externalizing and internalizing behaviors at 24 months of age. This suggests that the altered frontal functional connectivity in infants born to mothers whose depressive symptomatology increases in the early postnatal period compared to that during pregnancy may reflect a neural basis for the familial transmission of phenotypes associated with mood disorders, particularly in girls. PMID:27073881

  18. Nutrients, neurogenesis and brain ageing: From disease mechanisms to therapeutic opportunities.

    Science.gov (United States)

    Fidaleo, Marco; Cavallucci, Virve; Pani, Giovambattista

    2017-10-01

    Appreciation of the physiological relevance of mammalian adult neurogenesis has in recent years rapidly expanded from a phenomenon of homeostatic cell replacement and brain repair to the current view of a complex process involved in high order cognitive functions. In parallel, an array of endogenous or exogenous triggers of neurogenesis has also been identified, among which metabolic and nutritional cues have drawn significant attention. Converging evidence from animal and in vitro studies points to nutrient sensing and energy metabolism as major physiological determinants of neural stem cell fate, and modulators of the whole neurogenic process. While the cellular and molecular circuitries underlying metabolic regulation of neurogenesis are still incompletely understood, the key role of mitochondrial activity and dynamics, and the importance of autophagy have begun to be fully appreciated; moreover, nutrient-sensitive pathways and transducers such as the insulin-IGF cascade, the AMPK/mTOR axis and the transcription regulators CREB and Sirt-1 have been included, beside more established "developmental" signals like Notch and Wnt, in the molecular networks that dictate neural-stem-cell self-renewal, migration and differentiation in response to local and systemic inputs. Many of these nutrient-related cascades are deregulated in the contest of metabolic diseases and in ageing, and may contribute to impaired neurogenesis and thus to cognition defects observed in these conditions. Importantly, accumulating knowledge on the metabolic control of neurogenesis provides a theoretical framework for the trial of new or repurposed drugs capable of interfering with nutrient sensing as enhancers of neurogenesis in the context of neurodegeneration and brain senescence. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Effects of Neurotrophic Support and Amyloid-Targeted Combined Therapy on Adult Hippocampal Neurogenesis in a Transgenic Model of Alzheimer's Disease.

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    Christopher D Morrone

    Full Text Available Although it is recognized that multi-drug therapies may be necessary to combat AD, there is a paucity of preclinical proof of concept studies. We present a combination treatment paradigm, which temporally affects different aspects of Alzheimer's disease (AD-like pathology, specifically Aβ-toxicity and neurogenesis. At early stages of AD-like pathology, in TgCRND8 mice, we found that combating Aβ pathology with scyllo-inositol ameliorated deficits in neurogenesis. Older TgCRND8 mice with established amyloid load had decreased progenitor cell proliferation and survival compared to non-transgenic mice, regardless of scyllo-inositol treatment. The prolonged exposure to Aβ-pathology leads to deficits in the neurogenic niche, thus targeting Aβ alone is insufficient to rescue neurogenesis. To support the neurogenic niche, we combined scyllo-inositol treatment with leteprinim potassium (neotrofin, the latter of which stimulates neurotrophin expression. We show that the combination treatment of scyllo-inositol and neotrofin enhances neuronal survival and differentiation. We propose this proof of concept combination therapy of targeting Aβ-pathology and neurotrophin deficits as a potential treatment for AD.

  20. Effect of prenatal and postnatal malnutrition on intellectual functioning in early school-aged children in rural western China.

    Science.gov (United States)

    Li, Chao; Zhu, Ni; Zeng, Lingxia; Dang, Shaonong; Zhou, Jing; Yan, Hong

    2016-08-01

    The aim of this study was to evaluate the effect of prenatal and postnatal malnutrition on the intellectual functioning of early school-aged children. We followed the offspring of women who had participated in a trial of prenatal supplementation with different combinations of micronutrients and who remained resident in the study field. We measured their intellectual functioning using the Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for-age, and body mass index (BMI)-for-age were used as anthropometric nutritional status indices. Four of the 5 composite scores derived from the WISC-IV, except for working memory index (WMI), were significantly lower in low birth weight children after adjusting for confounds. All 5 composite scores, including full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), WMI, perceptual reasoning index (PRI), and processing speed index (PSI) were significant lower in stunted and underweight children. The differences in the means of WISC-IV test scores were greatest between stunted and nonstunted children. The means for FSIQ, VCI, WMI, PRI, and PSI were as follows: 5.88 (95% confidence interval [CI]: 2.84-8.92), 5.08 (95% CI: 1.12-8.41), 4.71 (95% CI: 1.78-7.66), 6.13 (95% CI: 2.83-9.44), and 5.81 (95% CI: 2.61-9.00). These means were lower in stunted children after adjusting for confounds. Our results suggest the important influences of low birth weight and postnatal malnutrition (stunting, low body weight) on intellectual functioning in early school-aged children.

  1. Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis.

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    Valentina Tosetti

    Full Text Available The complex architecture of adult brain derives from tightly regulated migration and differentiation of precursor cells generated during embryonic neurogenesis. Changes at transcriptional level of genes that regulate migration and differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR is a transcription factor that is already expressed during early embryonic days. However, AR role in the regulation of gene expression at early embryonic stage is yet to be determinate. Long non-coding RNA (lncRNA Sox2 overlapping transcript (Sox2OT plays a crucial role in gene expression control during development but its transcriptional regulation is still to be clearly defined. Here, using Bicalutamide in order to pharmacologically inactivated AR, we investigated whether AR participates in the regulation of the transcription of the lncRNASox2OTat early embryonic stage. We identified a new DNA binding region upstream of Sox2 locus containing three androgen response elements (ARE, and found that AR binds such a sequence in embryonic neural stem cells and in mouse embryonic brain. Our data suggest that through this binding, AR can promote the RNA polymerase II dependent transcription of Sox2OT. Our findings also suggest that AR participates in embryonic neurogenesis through transcriptional control of the long non-coding RNA Sox2OT.

  2. Early post-natal exposure to intermittent hypoxia in rodents is pro-inflammatory, impairs white matter integrity and alters brain metabolism

    Science.gov (United States)

    Darnall, Robert A.; Chen, Xi; Nemani, Krishnamurthy V.; Sirieix, Chrystelle M.; Gimi, Barjor; Knoblach, Susan; McEntire, Betty L.; Hunt, Carl E.

    2017-01-01

    Background Preterm infants are frequently exposed to intermittent hypoxia (IH) associated with apnea and periodic breathing that may result in inflammation and brain injury that later manifests as cognitive and executive function deficits. We used a rodent model to determine whether early postnatal exposure to IH would result in inflammation and brain injury. Methods Rat pups were exposed to IH from P2–P12. Control animals were exposed to room air. Cytokines were analyzed in plasma and brain tissue at P13 and P18. At P20–P22, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were performed. Results Pups exposed to IH had increased plasma Gro/CXCL1 and cerebellar IFN-γ and IL-1β at P13, and brainstem enolase at P18. DTI showed a decrease in FA and AD in the corpus callosum (CC) and cingulate gyrus and an increase in RD in the CC. MRS revealed decreases in NAA/Cho, Cr, Tau/Cr and Gly/Cr and increases in TCho and GPC in the brainstem and decreases in NAA/Cho in the hippocampus. Conclusions We conclude that early postnatal exposure to IH, similar in magnitude experienced in human preterm infants, is associated with evidence for pro-inflammatory changes, decreases in white matter integrity, and metabolic changes consistent with hypoxia. PMID:28388601

  3. Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis.

    Science.gov (United States)

    Ebrahimzadeh Bideskan, Alireza; Mohammadipour, Abbas; Fazel, Alireza; Haghir, Hossein; Rafatpanah, Houshang; Hosseini, Mahmoud; Rajabzadeh, Aliakbar

    2017-07-05

    The usage of Titanium dioxide nanoparticles (TiO 2 -NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO 2 -NPs during developmental period has been associated with hippocampal injury and with a decrease in learning and memory status of the offspring. However, little is known about its injury mechanism. This paper describes the in vivo neurotoxic effects of TiO 2 -NPs on rat offspring hippocampus during developmental period. Pregnant and lactating Wistar rats received intragastric TiO 2 -NPs (100mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21 and postnatal day (PD) 2 to (PD) 21 respectively. Animals in the control groups received an equal volume of distilled water via gavage. At the end of the treatment process, offspring were deeply anesthetized and sacrificed. Then brains of each group were collected and sections of the rat offspring's brains were stained using TUNEL staining (for detection of apoptotic cells) and immunostaining (for neurogenesis). Moreover, the right hippocampus (n=6 per each group) were removed from the right hemisphere for evaluating the expression of Bax and Bcl-2 level. Results of histopatological examination by TUNEL staining showed that maternal exposure to TiO 2 -NPs during pregnancy and lactation periods increased apoptotic cells significantly (P<0.01) in the offspring hippocampus. The immunolabeling of double cortin (DCX) protein as neurogenesis marker also showed that TiO 2 -NPs reduced neurogenesis in the hippocampus of the offspring (P<0.05). Moreover, in comparison with the control group, the mRNA levels of Bax and Bcl-2 in the TiO 2 -NPs group significantly increased and decreased, respectively (P<0.01). These findings provide strong evidence that maternal exposure to TiO 2 -NPs significantly impact hippocampal neurogenesis and apoptosis in the offspring. The potential impact of nanoparticle exposure for millions of pregnant mothers and

  4. Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases?

    Directory of Open Access Journals (Sweden)

    Suk-yu Yau

    2014-01-01

    Full Text Available Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain.

  5. Spatial relational memory requires hippocampal adult neurogenesis.

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    David Dupret

    Full Text Available The dentate gyrus of the hippocampus is one of the few regions of the mammalian brain where new neurons are generated throughout adulthood. This adult neurogenesis has been proposed as a novel mechanism that mediates spatial memory. However, data showing a causal relationship between neurogenesis and spatial memory are controversial. Here, we developed an inducible transgenic strategy allowing specific ablation of adult-born hippocampal neurons. This resulted in an impairment of spatial relational memory, which supports a capacity for flexible, inferential memory expression. In contrast, less complex forms of spatial knowledge were unaltered. These findings demonstrate that adult-born neurons are necessary for complex forms of hippocampus-mediated learning.

  6. Wnt/β-catenin signalling pathway mediated aberrant hippocampal neurogenesis in kainic acid-induced epilepsy.

    Science.gov (United States)

    Qu, Zhengyi; Su, Fang; Qi, Xueting; Sun, Jianbo; Wang, Hongcai; Qiao, Zhenkui; Zhao, Hong; Zhu, Yulan

    2017-10-01

    Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis with massive neuronal loss and severe gliosis. Aberrant neurogenesis has been shown in the epileptogenesis process of temporal lobe epilepsy. However, the molecular mechanisms underlying aberrant neurogenesis remain unclear. The roles of Wnt signalling cascade have been well established in neurogenesis during multiple aspects. Here, we used kainic acid-induced rat epilepsy model to investigate whether Wnt/β-catenin signalling pathway is involved in the aberrant neurogenesis in temporal lobe epilepsy. Immunostaining and western blotting results showed that the expression levels of β-catenin, Wnt3a, and cyclin D1, the key regulators in Wnt signalling pathway, were up-regulated during acute epilepsy induced by the injection of kainic acids, indicating that Wnt signalling pathway was activated in kainic acid-induced temporal lobe epilepsy. Moreover, BrdU labelling results showed that blockade of the Wnt signalling by knocking down β-catenin attenuated aberrant neurogenesis induced by kainic acids injection. Altogether, Wnt/β-catenin signalling pathway mediated hippocampal neurogenesis during epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy. Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis. Aberrant neurogenesis has been shown to involve in the epileptogenesis process of temporal lobe epilepsy. In the present study, we discovered that Wnt3a/β-catenin signalling pathway serves as a link between aberrant neurogenesis and underlying remodelling in the hippocampus, leading to temporal lobe epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous repair machinery?

    Science.gov (United States)

    Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

    2014-01-01

    Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.

  8. Neurogenesis in Aplysia californica resembles nervous system formation in vertebrates

    International Nuclear Information System (INIS)

    Jacob, M.H.

    1984-01-01

    The pattern of neurogenesis of the central nervous system of Aplysia californica was investigated by [ 3 H]thymidine autoradiography. Large numbers of animals at a series of early developmental stages were labeled with [ 3 H]thymidine for 24 or 48 hr and were subsequently sampled at specific intervals throughout the life cycle. I found that proliferative zones, consisting of columnar and placodal ectodermal cells, are established in regions of the body wall adjacent to underlying mesodermal cells. Mitosis in the proliferative zones generates a population of cells which leave the surface and migrate inward to join the nearby forming ganglia. Tracing specific [ 3 H]thymidine-labeled cells from the body wall to a particular ganglion and within the ganglion over time suggests that the final genomic replication of the neuronal precursors occurs before the cells join the ganglion while glial cell precursors and differentiating glial cells continue to divide within the ganglion for some time. Ultrastructural examination of the morphological features of the few mitosing cells observed within the Aplysia central nervous system supports this interpretation. The pattern of neurogenesis in the Aplysia central nervous system resembles the proliferation of cells in the neural tube and the migration of neural crest and ectodermal placode cells in the vertebrate nervous system but differs from the pattern described for other invertebrates

  9. The influence of postnatal handling on adult neuroendocrine and behavioural stress reactivity

    NARCIS (Netherlands)

    Meerlo, P; Horvath, KM; Nagy, GM; Bohus, B; Koolhaas, JM

    1999-01-01

    Environmental stimuli during early stages of life can influence the development of an organism and may result in permanent changes in adult behaviour and physiology. In the present study we investigated the influence of early postnatal handling on adult neuroendocrine and behavioural stress

  10. Oppositional effects of serotonin receptors 5-HT1a, 2 and 2c in the regulation of adult hippocampal neurogenesis

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    Friederike Klempin

    2010-07-01

    Full Text Available Serotonin (5-HT appears to play a major role in controlling adult hippocampal neurogenesis and thereby it is relevant for theories linking failing adult neurogenesis to the pathogenesis of major depression and the mechanisms of action of antidepressants. Serotonergic drugs lack acute effects on adult neurogenesis in many studies, which suggests a surprising long latency phase. Here we report that the selective serotonin reuptake inhibitor fluoxetine, which has no acute effect on precursor cell proliferation, causes the well-described increase in net neurogenesis upon prolonged treatment partly by promoting the survival and maturation of new postmitotic neurons. We hypothesized that this result is the cumulative effect of several 5-HT-dependent events in the course of adult neurogenesis. Thus, we used specific agonists and antagonists to 5-HT1a, 2, and 2c receptor subtypes to analyze their impact on different developmental stages. We found that 5-HT exerts acute and opposing effects on proliferation and survival or differentiation of precursor cells by activating the diverse receptor subtypes on different stages within the neuronal lineage in vivo. This was confirmed in vitro by demonstrating that 5-HT1a receptors are involved in self-renewal of precursor cells, whereas 5-HT2 receptors effect both proliferation and promote neuronal differentiation. We propose that under acute conditions 5-HT2 effects counteract the positive proliferative effect of 5-HT1a receptor activation. However, prolonged 5-HT2c receptor activation fosters an increase in late stage progenitor cells and early postmitotic neurons, leading to a net increase in adult neurogenesis. Our data indicate that serotonin does not show effect latency in the adult dentate gyrus. Rather, the delayed response to serotonergic drugs with respect to endpoints downstream of the immediate receptor activity is largely due to the initially antagonistic and un-balanced action of different 5-HT

  11. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    Science.gov (United States)

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Absence of the neurogenesis-dependent nuclear receptor TLX induces inflammation in the hippocampus.

    Science.gov (United States)

    Kozareva, Danka A; Hueston, Cara M; Ó'Léime, Ciarán S; Crotty, Suzanne; Dockery, Peter; Cryan, John F; Nolan, Yvonne M

    2017-08-20

    The orphan nuclear receptor TLX (Nr2e1) is a key regulator of hippocampal neurogenesis. Impaired adult hippocampal neurogenesis has been reported in neurodegenerative and psychiatric conditions including dementia and stress-related depression. Neuroinflammation is also implicated in the neuropathology of these disorders, and has been shown to negatively affect hippocampal neurogenesis. To investigate a role for TLX in hippocampal neuroinflammation, we assessed microglial activation in the hippocampus of mice with a spontaneous deletion of TLX. Results from our study suggest that a lack of TLX is implicated in deregulation of microglial phenotype and that consequently, the survival and function of newborn cells in the hippocampus is impaired. TLX may be an important target in understanding inflammatory-associated impairments in neurogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention.

    Science.gov (United States)

    Kim, Ah Hyun; Chun, Hye Jeong; Lee, Seulah; Kim, Hyung Sik; Lee, Jaewon

    2017-08-01

    Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. NF-κB Mediated Regulation of Adult Hippocampal Neurogenesis: Relevance to Mood Disorders and Antidepressant Activity

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    Valeria Bortolotto

    2014-01-01

    Full Text Available Adult hippocampal neurogenesis is a peculiar form of process of neuroplasticity that in recent years has gained great attention for its potential implication in cognition and in emotional behavior in physiological conditions. Moreover, a vast array of experimental studies suggested that adult hippocampal neurogenesis may be altered in various neuropsychiatric disorders, including major depression, where its disregulation may contribute to cognitive impairment and/or emotional aspects associated with those diseases. An intriguing area of interest is the potential influence of drugs on adult neurogenesis. In particular, several psychoactive drugs, including antidepressants, were shown to positively modulate adult hippocampal neurogenesis. Among molecules which could regulate adult hippocampal neurogenesis the NF-κB family of transcription factors has been receiving particular attention from our and other laboratories. Herein we review recent data supporting the involvement of NF-κB signaling pathways in the regulation of adult neurogenesis and in the effects of drugs that are endowed with proneurogenic and antidepressant activity. The potential implications of these findings on our current understanding of the process of adult neurogenesis in physiological and pathological conditions and on the search for novel antidepressants are also discussed.

  15. Fate of Cajal-Retzius neurons in the postnatal mouse neocortex

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    Tara G Chowdhury

    2010-03-01

    Full Text Available Cajal-Retzius (CR neurons play a critical role in cortical neuronal migration, but their exact fate after the completion of neocortical lamination remains a mystery. Histological evidence has been unable to unequivocally determine whether these cells die or undergo a phenotypic transformation to become resident interneurons of Layer 1 in the adult neocortex. To determine their ultimate fate, we performed chronic in vivo two-photon imaging of identified CR neurons during postnatal development in mice that express the green fluorescent protein (GFP under the control of the early B-cell factor 2 (Ebf2 promoter. We find that, after birth, virtually all CR neurons in mouse neocortex express Ebf2. Although postnatal CR neurons undergo dramatic morphological transformations, they do not migrate to deeper layers. Instead, their gradual disappearance from the cortex is due to apoptotic death during the second postnatal week. A small fraction of CR neurons present at birth survive into adulthood. We conclude that, in addition to orchestrating cortical layering, a subset of CR neurons must play other roles beyond the third postnatal week.

  16. Adult Hippocampal Neurogenesis is Impaired by Transient and Moderate Developmental Thyroid Hormone Disruption

    Science.gov (United States)

    Severe thyroid hormone (TH) deprivation during development impairs neurogenesis throughout the brain. The hippocampus also maintains a capacity for neurogenesis throughout life which is reduced in adult-onset hypothyroidism. This study examined hippocampal volume in the neonate a...

  17. BIRDS AS A MODEL TO STUDY ADULT NEUROGENESIS: BRIDGING EVOLUTIONARY, COMPARATIVE AND NEUROETHOLOGICAL APPROCHES

    Science.gov (United States)

    BARNEA, ANAT; PRAVOSUDOV, VLADIMIR

    2011-01-01

    During the last few decades evidence has demonstrated that adult neurogenesis is a well-preserved feature throughout the animal kingdom. In birds, ongoing neuronal addition occurs rather broadly, to a number of brain regions. This review describes adult avian neurogenesis and neuronal recruitment, discusses factors that regulate these processes, and touches upon the question of their genetic control. Several attributes make birds an extremely advantageous model to study neurogenesis. First, song learning exhibits seasonal variation that is associated with seasonal variation in neuronal turnover in some song control brain nuclei, which seems to be regulated via adult neurogenesis. Second, food-caching birds naturally use memory-dependent behavior in learning locations of thousands of food caches scattered over their home ranges. In comparison with other birds, food-caching species have relatively enlarged hippocampi with more neurons and intense neurogenesis, which appears to be related to spatial learning. Finally, migratory behavior and naturally occurring social systems in birds also provide opportunities to investigate neurogenesis. Such diversity of naturally-occurring memory-based behaviors, combined with the fact that birds can be studied both in the wild and in the laboratory, make them ideal for investigation of neural processes underlying learning. This can be done by using various approaches, from evolutionary and comparative to neuroethological and molecular. Finally, we connect the avian arena to a broader view by providing a brief comparative and evolutionary overview of adult neurogenesis and by discussing the possible functional role of the new neurons. We conclude by indicating future directions and possible medical applications. PMID:21929623

  18. Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice

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    Klaus Fabel

    2009-11-01

    Full Text Available Voluntary physical exercise (wheel running, RUN and environmental enrichment (ENR both stimulate adult hippocampal neurogenesis but do so by different mechanisms. RUN induces precursor cell proliferation, whereas ENR exerts a survival-promoting effect on newborn cells. In addition, continued RUN prevented the physiologically occurring age-related decline in precursor cell in the dentate gyrus but did not lead to a corresponding increase in net neurogenesis. We hypothesized that in the absence of appropriate cognitive stimuli the potential for neurogenesis could not be realized but that an increased potential by proliferating precursor cells due to RUN could actually lead to more adult neurogenesis if an appropriate survival-promoting stimulus follows the exercise. We thus asked whether a sequential combination of RUN and ENR (RUNENR would show additive effects that are distinct from the application of either paradigm alone. We found that the effects of 10 days of RUN followed by 35 days of ENR were additive in that the combined stimulation yielded an approximately 30% greater increase in new neurons than either stimulus alone, which also increased neurogenesis. Surprisingly, this result indicates that although overall the amount of proliferating cells in the dentate gyrus is poorly predictive of net adult neurogenesis, an increased neurogenic potential nevertheless provides the basis for a greater efficiency of the same survival-promoting stimulus. We thus propose that physical activity can “prime” the neurogenic region of the dentate gyrus for increased neurogenesis in the case the animal is exposed to an additional cognitive stimulus, here represented by the enrichment paradigm.

  19. First-time fathers' postnatal experiences and support needs: A descriptive qualitative study.

    Science.gov (United States)

    Shorey, Shefaly; Dennis, Cindy-Lee; Bridge, Shiho; Chong, Yap Seng; Holroyd, Eleanor; He, Hong-Gu

    2017-12-01

    To explore first-time fathers' postnatal experiences and support needs in the early postpartum period. The postnatal period is a stressful transition period for new fathers. It is imperative to understand their needs and experiences to provide appropriate support for them. The majority of previous studies were based in Western countries and explored fathers' needs during pregnancy and childbirth, with few studies conducted in the postnatal period. In Singapore, a multiracial society with differing paternal cultural values from its Western counterparts, there is considerable need to examine the experiences and needs of first-time fathers. A descriptive qualitative design was used. Data were collected from November 2015-January 2016. Fifteen first-time fathers were recruited from two postnatal wards of a public hospital, using a purposive sampling method. A semi-structured interview guide was used to conduct face-to-face interviews. A thematic analysis was conducted and ethics approval was sought for this study. Four overarching themes and seventeen subthemes were generated. The four overarching themes were: (1) No sense of reality to sense of responsibility; (2) Unprepared and challenged; (3) Support: needs, sources, experience and attitude; and (4) Future help for fathers. Fathers undergo a transition phase where they have unmet support needs during the early postnatal period. Understanding and addressing these needs may facilitate smooth transition to fatherhood. This study's findings can be used to involve fathers and design future supportive educational programs to promote positive parenting experiences and family dynamics. © 2017 John Wiley & Sons Ltd.

  20. Neurogenesis in the brain auditory pathway of a marsupial, the northern native cat (Dasyurus hallucatus)

    International Nuclear Information System (INIS)

    Aitkin, L.; Nelson, J.; Farrington, M.; Swann, S.

    1991-01-01

    Neurogenesis in the auditory pathway of the marsupial Dasyurus hallucatus was studied. Intraperitoneal injections of tritiated thymidine (20-40 microCi) were made into pouch-young varying from 1 to 56 days pouch-life. Animals were killed as adults and brain sections were prepared for autoradiography and counterstained with a Nissl stain. Neurons in the ventral cochlear nucleus were generated prior to 3 days pouch-life, in the superior olive at 5-7 days, and in the dorsal cochlear nucleus over a prolonged period. Inferior collicular neurogenesis lagged behind that in the medial geniculate, the latter taking place between days 3 and 9 and the former between days 7 and 22. Neurogenesis began in the auditory cortex on day 9 and was completed by about day 42. Thus neurogenesis was complete in the medullary auditory nuclei before that in the midbrain commenced, and in the medial geniculate before that in the auditory cortex commenced. The time course of neurogenesis in the auditory pathway of the native cat was very similar to that in another marsupial, the brushtail possum. For both, neurogenesis occurred earlier than in eutherian mammals of a similar size but was more protracted

  1. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

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    Dani Smith

    Full Text Available Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains.Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not.Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  2. Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life.

    Science.gov (United States)

    Smith, Dani; Aherrera, Angela; Lopez, Armando; Neptune, Enid; Winickoff, Jonathan P; Klein, Jonathan D; Chen, Gang; Lazarus, Philip; Collaco, Joseph M; McGrath-Morrow, Sharon A

    2015-01-01

    Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

  3. Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits.

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    Erika Navarrete

    Full Text Available Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB. We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1, pups were randomly assigned to one of the following conditions: intact pups (INT, intact pups fed by enteral gavage (INT+ENT, sham operated pups (SHAM, pups with unilateral lesions of the olfactory bulb (OBx-UNI, and pups with bilateral lesions of the olfactory bulb (OBx-BI. At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00, and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb.

  4. Prevalence and risk factors for postnatal depression in Sabah, Malaysia: a cohort study.

    Science.gov (United States)

    Mohamad Yusuff, Aza Sherin; Tang, Li; Binns, Colin W; Lee, Andy H

    2015-03-01

    Postnatal depression can have serious consequences for both the mother and infant. However, epidemiological data required to implement appropriate early prevention are still lacking in Malaysia. To investigate the prevalence of postnatal depression within six months postpartum and associated risk factors among women in Sabah, Malaysia. A prospective cohort study of 2072 women was conducted in Sabah during 2009-2010. Participants were recruited at 36-38 weeks of gestation and followed up at 1, 3 and 6 months postpartum. The presence of depressive symptoms was assessed using the validated Malay version of the Edinburgh Postnatal Depression Scale. Logistic regression analyses were performed to ascertain risk factors associated with postnatal depression. Overall, 14.3% of mothers (95% confidence interval (CI) 12.5-16.2%) had experienced depression within the first six months postpartum. Women depressed during pregnancy (odds ratio (OR) 3.71, 95% CI 2.46-5.60) and those with consistent worries about the newborn (OR 1.68, 95% CI 1.16-2.42) were more likely to suffer from depression after childbirth. Women whose husband assisted with infant care (OR 0.43, 95% CI 0.20-0.97) and mothers who were satisfied with their marital relationship (OR 0.27, 95% CI 0.09-0.81) appeared to incur a reduced risk of postnatal depression. A substantial proportion of mothers suffered from postnatal depression in Sabah, Malaysia. Screening and intervention programmes targeting vulnerable subgroups of women during antenatal and early postpartum periods are recommended to deal with the problem. Copyright © 2014 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  5. Neurogenesis in the brain stem of the rabbit: an autoradiographic study

    International Nuclear Information System (INIS)

    Oblinger, M.M.; Das, G.D.

    1981-01-01

    With the aid of ( 3 H)-thymidine autoradiography, neurogenesis was documented in the nuclear groups of the medulla oblongata, pons, and mid-brain, as well as in the brain stem reticular formation of the rabbit. Following single injections of ( 3 H)-thymidine, counts were taken of intensely labeled neurons within the nuclei of the functional columns related to the cranial nerves, nuclei of several other functional classifications, and nuclei that did not fit into a functional category. In the brain stem as a whole, neurogenesis was found to occur between days 10.0 and 18.5 of gestation: however, the majority of nuclei studied contained intensely neurons only between days 12.0 and 15.0. Only in the pontine nucleus and the tectum were intensely labeled cells observed as late as day 18.5. Directional gradients of histogenesis were often observed within, as well as between, various nuclei. Within the nuclear columns related to the cranial nerves, a clear mediolateral spread of neurogenesis was observable such that nuclei of the motor columns reached a peak in neurogenesis before those in the sensory columns. Likewise, a mediolateral proliferation pattern was seen in the brain stem reticular formation. Other individual directional gradients were discernible; however, in the brain stem as a whole, distinct overall gradients were not observable. In many individual nuclei, gradients in neuron size were observed such that large neurons preferentially arose prior to smaller neurons. Information pertaining to gradients in neurogenesis, as well as to relationships among functionally related nuclei, are discussed

  6. Mouse embryonic retina delivers information controlling cortical neurogenesis.

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    Ciro Bonetti

    2010-12-01

    Full Text Available The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded, the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal. Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system.

  7. Endogenous neurogenesis in the human brain following cerebral infarction.

    Science.gov (United States)

    Minger, Stephen L; Ekonomou, Antigoni; Carta, Eloisa M; Chinoy, Amish; Perry, Robert H; Ballard, Clive G

    2007-01-01

    Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.

  8. Interleukin-1β: A New Regulator of the Kynurenine Pathway Affecting Human Hippocampal Neurogenesis

    Science.gov (United States)

    Zunszain, Patricia A; Anacker, Christoph; Cattaneo, Annamaria; Choudhury, Shanas; Musaelyan, Ksenia; Myint, Aye Mu; Thuret, Sandrine; Price, Jack; Pariante, Carmine M

    2012-01-01

    Increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. Here, we show for the first time how IL-1β, a pro-inflammatory cytokine shown to be increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. IL-1β was detrimental to neurogenesis, as shown by a decrease in the number of doublecortin-positive neuroblasts (−28%), and mature, microtubule-associated protein-2-positive neurons (−36%). Analysis of the enzymes that regulate the kynurenine pathway showed that IL-1β induced an upregulation of transcripts for indolamine-2,3-dioxygenase (IDO), kynurenine 3-monooxygenase (KMO), and kynureninase (42-, 12- and 30-fold increase, respectively, under differentiating conditions), the enzymes involved in the neurotoxic arm of the kynurenine pathway. Moreover, treatment with IL-1β resulted in an increase in kynurenine, the catabolic product of IDO-induced tryptophan metabolism. Interestingly, co-treatment with the KMO inhibitor Ro 61-8048 reversed the detrimental effects of IL-1β on neurogenesis. These observations indicate that IL-1β has a critical role in regulating neurogenesis whereas affecting the availability of tryptophan and the production of enzymes conducive to toxic metabolites. Our results suggest that inhibition of the kynurenine pathway may provide a new therapy to revert inflammatory-induced reduction in neurogenesis. PMID:22071871

  9. Early-Life Stress Does Not Aggravate Spatial Memory or the Process of Hippocampal Neurogenesis in Adult and Middle-Aged APP/PS1 Mice

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    Lianne Hoeijmakers

    2018-03-01

    Full Text Available Life-time experiences are thought to influence the risk to develop the neurodegenerative disorder Alzheimer’s disease (AD. In particular, early-life stress (ES may modulate the onset and progression of AD. There is recent evidence by our group and others that AD-related neuropathological progression and the associated neuroimmune responses are modulated by ES in the classic APPswe/PS1dE9 mouse model for AD. We here extend our previous study on ES mediated modulation of neuropathology and neuroinflammation and address in the same cohort of mice whether ES accelerates and/or aggravates AD-induced cognitive decline and alterations in the process of adult hippocampal neurogenesis (AHN, a form of brain plasticity. Chronic ES was induced by limiting bedding and nesting material during the first postnatal week and is known to induce cognitive deficits by 4 months in wild type (WT mice. The onset of cognitive decline in APP/PS1 mice generally starts around 6 months of age. We here tested mice at ages 2–4 months to study acceleration and at ages 8–10 months for aggravation of the APP/PS1 phenotype. ES-exposed WT and APP/PS1 mice were able to perform the object recognition (ORT and location tasks (OLT at 2 months of age. Interestingly, at 3 months, ES induced impairments in the performance of the OLT in WT, but not in APP/PS1 mice. APP/PS1 mice exhibited alterations in hippocampal cell proliferation and differentiation, but ES exposure did not further change this. At 9 months, APP/PS1 mice exhibited impaired performance in the Morris Water Maze (MWM task, as well as reductions in markers of the AHN process, which were not further modulated by ES exposure. In addition, we observed a so far unreported hyperactivity in ES-exposed mice at 8 months of age, which hampered assessment of cognitive functions in the ORT and OLT. In conclusion, while ES has been reported to modulate AD neuropathology and neuroinflammation before, it failed to accelerate or

  10. Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation

    International Nuclear Information System (INIS)

    Itahashi, Megu; Abe, Hajime; Tanaka, Takeshi; Mizukami, Sayaka; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

    2015-01-01

    Highlights: • The effect of maternal exposure to HCP on rat hippocampal neurogenesis was examined. • HCP induces myelin vacuolation of nerve tracts in the septal–hippocampal pathway. • Myelin changes suppress Chrnb2-mediated cholinergic inputs to the dentate gyrus. • SGZ apoptosis occurs via the mitochondrial pathway and targets type-2b cells. • Dysfunction of cholinergic inputs is related to type-2b SGZ cell apoptosis. - Abstract: Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300 ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2 + progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling + apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300 ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300 ppm HCP. Neurogenesis may be affected by dysfunction

  11. Inhibitory effects of caffeine on hippocampal neurogenesis and function.

    Science.gov (United States)

    Han, Myoung-Eun; Park, Kyu-Hyun; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Kim, Hak-Jin; Oh, Sae-Ock

    2007-05-18

    Caffeine is one of the most extensively consumed psychostimulants in the world. However, compared to short-term effects of caffeine, the long-term effects of caffeine consumption on learning and memory are poorly characterized. The present study found that long-term consumption of low dose caffeine (0.3 g/L) slowed hippocampus-dependent learning and impaired long-term memory. Caffeine consumption for 4 weeks also significantly reduced hippocampal neurogenesis compared to controls. From these results, we concluded that long-term consumption of caffeine could inhibit hippocampus-dependent learning and memory partially through inhibition of hippocampal neurogenesis.

  12. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

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    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  13. Maternal postnatal mental health and later emotional-behavioural development of children: the mediating role of parenting behaviour.

    Science.gov (United States)

    Giallo, R; Cooklin, A; Wade, C; D'Esposito, F; Nicholson, J M

    2014-05-01

    Maternal postnatal mental health difficulties have been associated with poor outcomes for children. One mechanism by which parent mental health can impact on children's outcomes is via its effects on parenting behaviour. The longitudinal relationships between maternal postnatal distress, parenting warmth, hostility and child well-being at age seven were examined for 2200 families participating in a population-based longitudinal study of Australian children. The relationship between postnatal distress and children's later emotional-behavioural development was mediated by parenting hostility, but not parenting warmth, even after accounting for concurrent maternal mental health. Postnatal distress was more strongly associated with lower parenting warmth for mothers without a past history of depression compared with mothers with a past history of depression. These findings underscore the contribution of early maternal well-being to later parenting and child outcomes, highlighting the importance of mental health and parenting support in the early parenting years. Implications for policy and practice are discussed. © 2013 John Wiley & Sons Ltd.

  14. Prenatal hydronephrosis: postnatal evaluation and management.

    Science.gov (United States)

    Vemulakonda, Vijaya; Yiee, Jenny; Wilcox, Duncan T

    2014-08-01

    Congenital hydronephrosis is one of the most common anomalies identified on antenatal ultrasound. The underlying etiology of congenital hydronephrosis is multifold, ranging from transient hydronephrosis in utero to clinically significant congenital anomalies of the kidney and urinary tract. While traditional management of hydronephrosis was aimed at relieving symptoms, the advent of routine prenatal ultrasound has led to a shift in the goal of treatment to prevention of renal injury in the asymptomatic patient. However, despite this focus on renal preservation, the diagnostic criteria for identification of children "at risk" for renal damage that can be alleviated by surgical treatment remain a subject of debate. Both antenatal and postnatal imaging studies have been evaluated as indicators for potential reversible renal damage and have been used as potential indicators of the need for surgical intervention. The aim of this review is to discuss the current literature regarding the role of postnatal clinical and radiographic evaluation to identify children who may benefit from early surgical intervention.

  15. Deletion of running-induced hippocampal neurogenesis by irradiation prevents development of an anxious phenotype in mice.

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    Johannes Fuss

    2010-09-01

    Full Text Available Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box. Reducing neurogenesis by focalized irradiation of the hippocampus abolished this exercise-induced increase of anxiety, suggesting a direct implication of hippocampal neurogenesis in this phenotype. On the other hand, irradiated mice explored less frequently the lit compartment of the dark-light box test irrespective of wheel running, suggesting that irradiation per se induced anxiety as well. Thus, our data suggest that intermediate levels of neurogenesis are related to the lowest levels of anxiety. Moreover, using c-Fos immunocytochemistry as cellular activity marker, we observed significantly different induction patterns between runners and sedentary controls when exposed to a strong anxiogenic stimulus. Again, this effect was altered by irradiation. In contrast, the well-known induction of brain-derived neurotrophic factor (BDNF by voluntary exercise was not disrupted by focal irradiation, indicating that hippocampal BDNF levels were not correlated with anxiety under our experimental conditions. In summary, our data demonstrate to our knowledge for the first time that increased neurogenesis has a causative implication in the induction of anxiety.

  16. Acupuncture for neurogenesis in experimental ischemic stroke: a systematic review and meta-analysis.

    Science.gov (United States)

    Lu, Lin; Zhang, Xiao-guang; Zhong, Linda L D; Chen, Zi-xian; Li, Yan; Zheng, Guo-qing; Bian, Zhao-xiang

    2016-01-20

    Acupuncture has been used for patients with stroke and post-stroke rehabilitation for thousands of years. Previous studies reported that acupuncture enhanced stroke recovery through neurogenesis. Hence, we conducted a systematic review and meta-analysis for preclinical studies to assess the current evidence for acupuncture effect on neurogenesis in treating ischaemic stroke. Studies were obtained from six databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, and Chinese Biomedical Literature Database, Ultimately, 34 studies containing 1617 animals were identified. Neurogenesis markers of Brdu, Nestin, PSA-NCAM, NeuN and GFAP were selected as major outcomes. The pooled results of 15 studies marked with Brdu showed significant effects of acupuncture for improving proliferation when compared with control groups (P acupuncture for increasing proliferation when compared with control groups (P acupuncture for enhancing migration when compared with control groups (P acupuncture for stimulating differentiation when compared with control groups (P acupuncture is a prospective therapy targeting neurogenesis for ischemic stroke.

  17. The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats

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    Karina H. Solís

    2017-12-01

    Full Text Available Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H1 receptor (H1R which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H1R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2 and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H1R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H1R expression by qRT-PCR and Western blot and, finally, we tested H1R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers and partially reverted the increased level of MAP2 protein at E14, concluding that H1R have an important role in the increased neurogenesis within the dorsal telencephalon

  18. Correlations between Hippocampal Neurogenesis and Metabolic Indices in Adult Nonhuman Primates

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    Tarique D. Perera

    2011-01-01

    Full Text Available Increased neurogenesis in feeding centers of the murine hypothalamus is associated with weight loss in diet-induced obese rodents (Kokoeva et al., 2005 and Matrisciano et al., 2010, but this relationship has not been examined in other species. Postmortem hippocampal neurogenesis rates and premortem metabolic parameters were statistically analyzed in 8 chow-fed colony-reared adult bonnet macaques. Dentate gyrus neurogenesis, reflected by the immature neuronal marker, doublecortin (DCX, and expression of the antiapoptotic gene factor, B-cell lymphoma 2 (BCL-2, but not the precursor proliferation mitotic marker, Ki67, was inversely correlated with body weight and crown-rump length. DCX and BCL-2 each correlated positively with blood glucose level and lipid ratio (total cholesterol/high-density lipoprotein. This study demonstrates that markers of dentate gyrus neuroplasticity correlate with metabolic parameters in primates.

  19. The temporal expression pattern of alpha-synuclein modulates olfactory neurogenesis in transgenic mice.

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    Sebastian R Schreglmann

    Full Text Available Adult neurogenesis mirrors the brain´s endogenous capacity to generate new neurons throughout life. In the subventricular zone/ olfactory bulb system adult neurogenesis is linked to physiological olfactory function and has been shown to be impaired in murine models of neuronal alpha-Synuclein overexpression. We analyzed the degree and temporo-spatial dynamics of adult olfactory bulb neurogenesis in transgenic mice expressing human wild-type alpha-Synuclein (WTS under the murine Thy1 (mThy1 promoter, a model known to have a particularly high tg expression associated with impaired olfaction.Survival of newly generated neurons (NeuN-positive in the olfactory bulb was unchanged in mThy1 transgenic animals. Due to decreased dopaminergic differentiation a reduction in new dopaminergic neurons within the olfactory bulb glomerular layer was present. This is in contrast to our previously published data on transgenic animals that express WTS under the control of the human platelet-derived growth factor β (PDGF promoter, that display a widespread decrease in survival of newly generated neurons in regions of adult neurogenesis, resulting in a much more pronounced neurogenesis deficit. Temporal and quantitative expression analysis using immunofluorescence co-localization analysis and Western blots revealed that in comparison to PDGF transgenic animals, in mThy1 transgenic animals WTS is expressed from later stages of neuronal maturation only but at significantly higher levels both in the olfactory bulb and cortex.The dissociation between higher absolute expression levels of alpha-Synuclein but less severe impact on adult olfactory neurogenesis in mThy1 transgenic mice highlights the importance of temporal expression characteristics of alpha-Synuclein on the maturation of newborn neurons.

  20. Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH

    DEFF Research Database (Denmark)

    Main, Katharina M; Schmidt, Ida M; Toppari, Jorma

    2002-01-01

    BACKGROUND: Patients with hypogonadotropic hypogonadism may be diagnosed shortly after birth because of micropenis and cryptorchidism, combined with subnormal LH and FSH concentrations during the postnatal period. OBJECTIVE: To investigate whether treating these patients with gonadotropins postna...... observed. CONCLUSIONS: Gonadotropin treatment in an infant with hypogonadotropic hypogonadism succeeded in inducing an increase in inhibin B and testicular growth.......BACKGROUND: Patients with hypogonadotropic hypogonadism may be diagnosed shortly after birth because of micropenis and cryptorchidism, combined with subnormal LH and FSH concentrations during the postnatal period. OBJECTIVE: To investigate whether treating these patients with gonadotropins...... the normal range (0.05-0.17 IU/l and 79-112 pg/ml respectively). METHODS: From 7.9 to 13.7 months of age, the patient was treated with recombinant human LH and FSH in doses of 20 and 21.3 IU s.c. twice weekly respectively. RESULTS: During treatment concentrations of LH, FSH, inhibin B and estradiol increased...

  1. Amyloid β Is Not the Major Factor Accounting for Impaired Adult Hippocampal Neurogenesis in Mice Overexpressing Amyloid Precursor Protein

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    Hongyu Pan

    2016-10-01

    Full Text Available Adult hippocampal neurogenesis was impaired in several Alzheimer's disease models overexpressing mutant human amyloid precursor protein (hAPP. However, the effects of wild-type hAPP on adult neurogenesis and whether the impaired adult hippocampal neurogenesis was caused by amyloid β (Aβ or APP remained unclear. Here, we found that neurogenesis was impaired in the dentate gyrus (DG of adult mice overexpressing wild-type hAPP (hAPP-I5 compared with controls. However, the adult hippocampal neurogenesis was more severely impaired in hAPP-I5 than that in hAPP-J20 mice, which express similar levels of hAPP mRNA but much higher levels of Aβ. Furthermore, reducing Aβ levels did not affect the number of doublecortin-positive cells in the DG of hAPP-J20 mice. Our results suggested that hAPP was more likely an important factor inhibiting adult neurogenesis, and Aβ was not the major factor affecting neurogenesis in the adult hippocampus of hAPP mice.

  2. Hypothalamic neuroendocrine circuitry is programmed by maternal obesity: interaction with postnatal nutritional environment.

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    Hui Chen

    Full Text Available OBJECTIVE: Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY and suppressor proopiomelanocortin (POMC in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD consumption are unclear. RESEARCH DESIGN AND METHODS: Female Sprague Dawley rats were exposed to chow or HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1, litters were adjusted to 3/litter to induce postnatal overnutrition (vs. 12 in control. At postnatal day 20, half of the rats from each maternal group were weaned onto chow or HFD for 15 weeks. Hypothalamic appetite regulators, and fuel (glucose and lipid metabolic markers were measured. RESULTS: Offspring from obese dams gained more weight than those from lean dams independent of post-weaning diet. Maternal obesity interacted with post-weaning HFD consumption to cause greater levels of hyperphagia, adiposity, hyperlipidemia, and glucose intolerance in offspring. This was linked to increased hypothalamic NPY signaling and leptin resistance in adult offspring. Litter size reduction had a detrimental impact on insulin and adiponectin, while hypothalamic NPY and POMC mRNA expression were suppressed in the face of normal energy intake and weight gain. CONCLUSIONS: Maternal obesity, postnatal litter size reduction and post-weaning HFD consumption caused obesity via different neuroendocrine mechanism. There were strong additive effects of maternal obesity and post-weaning HFD consumption to increase the metabolic disorders in offspring.

  3. Postnatal Psychosocial Assessment and Clinical Decision-Making, a Descriptive Study.

    Science.gov (United States)

    Sims, Deborah; Fowler, Cathrine

    2018-05-18

    The aim of this study is to describe experienced child and family health nurses' clinical decision-making during a postnatal psychosocial assessment. Maternal emotional wellbeing in the postnatal year optimises parenting and promotes infant development. Psychosocial assessment potentially enables early intervention and reduces the risk of a mental disorder occurring during this time of change. Assessment accuracy, and the interventions used are determined by the standard of nursing decision-making. A qualitative methodology was employed to explore decision-making behaviour when conducting a postnatal psychosocial assessment. This study was conducted in an Australian early parenting organisation. Twelve experienced child and family health nurses were interviewed. A detailed description of a postnatal psychosocial assessment process was obtained using a critical incident technique. Template analysis was used to determine the information domains the nurses accessed, and content analysis was used to determine the nurses' thinking strategies, to make clinical decisions from this assessment. The nurses described 24 domains of information and used 17 thinking strategies, in a variety of combinations. The four information domains most commonly used were parenting, assessment tools, women-determined issues and sleep. The seven thinking strategies most commonly used were searching for information, forming relationships between the information, recognising a pattern, drawing a conclusion, setting priorities, providing explanations for the information and judging the value of the information. The variety and complexity of the clinical decision-making involved in postnatal psychosocial assessment confirms that the nurses use information appropriately and within their scope of nursing practice. The standard of clinical decision-making determines the results of the assessment and the optimal access to care. Knowledge of the information domains and the decision-making strategies

  4. An Aminopropyl Carbazole Derivative Induces Neurogenesis by Increasing Final Cell Division in Neural Stem Cells.

    Science.gov (United States)

    Shin, Jae-Yeon; Kong, Sun-Young; Yoon, Hye Jin; Ann, Jihyae; Lee, Jeewoo; Kim, Hyun-Jung

    2015-07-01

    P7C3 and its derivatives, 1-(3,6-dibromo-9H-carbazol-9-yl)-3-(p-tolylamino)propan-2-ol (1) and N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-hydroxypropyl)-N-(3-methoxyphenyl)-4-methylbenzenesulfonamide (2), were previously reported to increase neurogenesis in rat neural stem cells (NSCs). Although P7C3 is known to increase neurogenesis by protecting newborn neurons, it is not known whether its derivatives also have protective effects to increase neurogenesis. In the current study, we examined how 1 induces neurogenesis. The treatment of 1 in NSCs increased numbers of cells in the absence of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2), while not affecting those in the presence of growth factors. Compound 1 did not induce astrocytogenesis during NSC differentiation. 5-Bromo-2'-deoxyuridine (BrdU) pulsing experiments showed that 1 significantly enhanced BrdU-positive neurons. Taken together, our data suggest that 1 promotes neurogenesis by the induction of final cell division during NSC differentiation.

  5. Targeted surveillance for postnatal hearing loss: a program evaluation.

    Science.gov (United States)

    Beswick, Rachael; Driscoll, Carlie; Kei, Joseph; Glennon, Shirley

    2012-07-01

    The importance of monitoring hearing throughout early childhood cannot be understated. However, there is a lack of evidence available regarding the most effective method of monitoring hearing following the newborn screen. The goal of this study was to describe a targeted surveillance program using a risk factor registry to identify children with a postnatal hearing loss. All children who were born in Queensland, Australia between September 2004 and December 2009, received a bilateral 'pass' on newborn hearing screening, and had at least one risk factor, were referred for targeted surveillance and were included in this study. The cohort was assessed throughout early childhood in accordance with Queensland's diagnostic assessment protocols. During the study period, 7320 (2.8% of 261,328) children were referred for targeted surveillance, of which 56 were identified with a postnatal hearing loss (0.77%). Of these, half (50.0%) were identified with a mild hearing loss, and 64.3% were identified with a sensorineural hearing loss. In regards to risk factors, syndrome, craniofacial anomalies, and severe asphyxia had the highest yield of positive cases of postnatal hearing loss for children referred for targeted surveillance, whereas, low birth weight, bacterial meningitis, and professional concern had a particularly low yield. Limitations of the targeted surveillance program were noted and include: (1) a lost contact rate of 32.4%; (2) delays in first surveillance assessment; (3) a large number of children who required on-going monitoring; and (4) extensive diagnostic assessments were completed on children with normal hearing. Examination of the lost contact rate revealed indigenous children were more likely to be documented as lost contact. In addition, children with one risk factor only were significantly more likely to not attend a surveillance appointment. Positive cases of postnatal hearing loss were detected through the targeted surveillance program. However, the

  6. Clonidine treatment delays postnatal motor development and blocks short-term memory in young mice.

    Directory of Open Access Journals (Sweden)

    Cristina Calvino-Núñez

    Full Text Available During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

  7. Macrophage-Mediated Glial Cell Elimination in the Postnatal Mouse Cochlea

    Directory of Open Access Journals (Sweden)

    LaShardai N. Brown

    2017-12-01

    Full Text Available Hearing relies on the transmission of auditory information from sensory hair cells (HCs to the brain through the auditory nerve. This relay of information requires HCs to be innervated by spiral ganglion neurons (SGNs in an exclusive manner and SGNs to be ensheathed by myelinating and non-myelinating glial cells. In the developing auditory nerve, mistargeted SGN axons are retracted or pruned and excessive cells are cleared in a process referred to as nerve refinement. Whether auditory glial cells are eliminated during auditory nerve refinement is unknown. Using early postnatal mice of either sex, we show that glial cell numbers decrease after the first postnatal week, corresponding temporally with nerve refinement in the developing auditory nerve. Additionally, expression of immune-related genes was upregulated and macrophage numbers increase in a manner coinciding with the reduction of glial cell numbers. Transient depletion of macrophages during early auditory nerve development, using transgenic CD11bDTR/EGFP mice, resulted in the appearance of excessive glial cells. Macrophage depletion caused abnormalities in myelin formation and transient edema of the stria vascularis. Macrophage-depleted mice also showed auditory function impairment that partially recovered in adulthood. These findings demonstrate that macrophages contribute to the regulation of glial cell number during postnatal development of the cochlea and that glial cells play a critical role in hearing onset and auditory nerve maturation.

  8. Supplementation with fish oil and coconut fat prevents prenatal stress-induced changes in early postnatal development.

    Science.gov (United States)

    Borsonelo, Elizabethe C; Suchecki, Deborah; Calil, Helena Maria; Galduróz, José Carlos F

    2011-08-01

    Adequate development of the central nervous system depends on prenatal and postnatal factors. On one hand, prenatal stress (PNS) has been implicated in impaired development of the offspring. On other hand, nutritional factors during pregnancy and lactation can influence fetal and postnatal growth. This study assessed the postnatal development of rat offspring exposed to PNS, which consisted of restraint and bright lights, 3 times/day, from days 14 to 20 of pregnancy, whose mothers were fed different diets during pregnancy and lactation: regular diet, diet supplemented with coconut fat or fish oil. When pregnancy was confirmed, they were distributed into control (CTL) or PNS groups. At birth, PNS males and females weighed less than those in the group CTL. At 21 days of age, this alteration was no longer observed with fish oil and coconut fat groups. PNS and coconut fat diet induced increased locomotor activity in 13 day old male and female pups, and this effect was prevented by fish oil supplementation only in females. In conclusion, postnatal development from birth to weaning was influenced by PNS and diet and some of those alterations were prevented by coconut fat and fish oil. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  9. NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction.

    Science.gov (United States)

    Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee

    2013-04-01

    Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.

  10. Duodenal Ca2+ absorption is not stimulated by calcitriol during early postnatal development of pigs.

    Science.gov (United States)

    Schroeder, B; Dahl, M R; Breves, G

    1998-08-01

    The role of calcitriol in stimulating intestinal active Ca2+ absorption during postnatal life was studied in newborn, suckling, and weaned control (Con) piglets and piglets suffering from inherited calcitriol deficiency (Def piglets). In addition, a group of Def piglets was treated with vitamin D3 (Def-D3 piglets), which normalized plasma calcitriol levels. Regardless of age, duodenal calbindin-D9k concentrations ranged between 1,839 and 2,846 microg/g mucosa in Con piglets, between 821 and 1,219 microg/g mucosa in Def piglets, and between 2,960 and 3,692 microg/g mucosa in Def-D3 animals. In weaned animals, active Ca2+ absorption as calculated from in vitro 45Ca2+ flux rate measurements in Ussing chambers could be related to calbindin-D9k levels. Thus active Ca2+ absorption was completely absent in Def animals but was reconstituted in Def-D3 animals. In contrast, in newborn Def piglets active Ca2+ absorption functioned normally despite the low plasma calcitriol and mucosal calbindin-D9k levels and could not be affected by treatment with vitamin D3. Similar results were obtained from suckling Def piglets. The microtubule-disrupting agent colchicine caused significant inhibition of transepithelial net Ca2+ absorption in duodenal epithelia from newborn piglets without exerting an effect in suckling and weaned animals. Colchicine had no effect on Ca2+ uptake across the brush border membrane of mucosal enterocytes or on glucose-dependent electrogenic net ion flux rates in duodenal preparations from newborn Con piglets. In conclusion, our findings reveal intestinal active Ca2+ absorption during early postnatal life of pigs that involves calcitriol-independent mechanisms and that may include intact microtubule actions.

  11. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    International Nuclear Information System (INIS)

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-01-01

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life

  12. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    Energy Technology Data Exchange (ETDEWEB)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  13. Deficient plasticity in the hippocampus and the spiral of addiction: focus on adult neurogenesis.

    Science.gov (United States)

    Canales, Juan J

    2013-01-01

    Addiction is a complex neuropsychiatric disorder which causes disruption at multiple levels, including cognitive, emotional, and behavioral domains. Traditional biological theories of addiction have focused on the mesolimbic dopamine pathway and the nucleus accumbens as anatomical substrates mediating addictive-like behaviors. More recently, we have begun to recognize the engagement and dynamic influence of a much broader circuitry which encompasses the frontal cortex, the amygdala, and the hippocampus. In particular, neurogenesis in the adult hippocampus has become a major focus of attention due to its ability to influence memory, motivation, and affect, all of which are disrupted in addiction. First, I summarize toxicological data that reveal strongly suppressive effects of drug exposure on adult hippocampal neurogenesis. Then, I discuss the impact of deficient neurogenesis on learning and memory function, stress responsiveness and affective behavior, as they relate to addiction. Finally, I examine recent behavioral observations that implicate neurogenesis in the adult hippocampus in the emergence and maintenance of addictive behavior. The evidence reviewed here suggests that deficient neurogenesis is associated with several components of the downward spiraling loop that characterizes addiction, including elevated sensitivity to drug-induced reward and reinforcement, enhanced neurohormonal responsiveness, emergence of a negative affective state, memory impairment, and inflexible behavior.

  14. Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis.

    Science.gov (United States)

    von Rüden, E-L; Avemary, J; Zellinger, C; Algermissen, D; Bock, P; Beineke, A; Baumgärtner, W; Stein, V M; Tipold, A; Potschka, H

    2012-08-01

    Despite knowledge about the impact of brain inflammation on hippocampal neurogenesis, data on the influence of virus encephalitis on dentate granule cell neurogenesis are so far limited. Canine distemper is considered an interesting model of virus encephalitis, which can be associated with a chronic progressing disease course and can cause symptomatic seizures. To determine the impact of canine distemper virus (CDV) infection on hippocampal neurogenesis, we compared post-mortem tissue from dogs with infection with and without seizures, from epileptic dogs with non-viral aetiology and from dogs without central nervous system diseases. The majority of animals with infection and with epilepsy of non-viral aetiology exhibited neuronal progenitor numbers below the age average in controls. Virus infection with and without seizures significantly decreased the mean number of neuronal progenitor cells by 43% and 76% as compared to age-matched controls. Ki-67 labelling demonstrated that hippocampal cell proliferation was neither affected by infection nor by epilepsy of non-viral aetiology. Analysis of CDV infection in cells expressing caspase-3, doublecortin or Ki-67 indicated that infection of neuronal progenitor cells is extremely rare and suggests that infection might damage non-differentiated progenitor cells, hamper neuronal differentiation and promote glial differentiation. A high inter-individual variance in the number of lectin-reactive microglial cells was evident in dogs with distemper infection. Statistical analyses did not reveal a correlation between the number of lectin-reactive microglia cells and neuronal progenitor cells. Our data demonstrate that virus encephalitis with and without seizures can exert detrimental effects on hippocampal neurogenesis, which might contribute to long-term consequences of the disease. The lack of a significant impact of distemper virus on Ki-67-labelled cells indicates that the infection affected neuronal differentiation and

  15. Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity

    DEFF Research Database (Denmark)

    Slidsborg, Carina; Jensen, Louise Bering; Rasmussen, Steen Christian

    2017-01-01

    Background To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP). Methods This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national registers...

  16. Birth weight and postnatal growth in preterm born children are associated with cortisol in early infancy, but not at age 8 years.

    Science.gov (United States)

    Ruys, Charlotte A; van der Voorn, Bibian; Lafeber, Harrie N; van de Lagemaat, Monique; Rotteveel, Joost; Finken, Martijn J J

    2017-08-01

    Preterm birth has been associated with altered hypothalamic-pituitary-adrenal (HPA-) axis activity as well as cardiometabolic diseases and neurodevelopmental impairments later in life. We assessed cortisol from term age to age 8 y in children born preterm, to explore the development of HPA-axis activity in association with intrauterine and early-postnatal growth until 6 mo. corrected age. In 152 children born at a gestational age ≤32 wks. and/or with a birth weight ≤1,500g, random serum cortisol was assessed at term age (n=150), 3 mo. (n=145) and 6 mo. corrected age (n=144), and age 8 y (n=59). Salivary cortisol was assessed at age 8 y (n=75): prior to bedtime, at awakening, 15min after awakening, and before lunch. Cortisol was analyzed in association with birth weight-standard deviation score (SDS), being born small for gestational age (SGA), and combinations of intrauterine and postnatal growth: appropriate for gestational age (AGA) with or without growth restriction (AGA GR+ or AGA GR-) at 6 mo. corrected age, and SGA with or without catch-up growth (SGA CUG+ or SGA CUG-) at 6 mo. corrected age. Cross-sectional associations at all time points were analyzed using linear regression, and longitudinal associations were analyzed using generalized estimating equations. Longitudinally, birth weight-SDS was associated with cortisol (β [95%CI]): lower cortisol over time was seen in infants with a birth weight ≤-2 SDS (-50.69 [-94.27; -7.11], p=0.02), infants born SGA (-29.70 [-60.58; 1.19], p=0.06), AGA GR+ infants (-55.10 [-106.02; -4.17], p=0.03) and SGA CUG- infants (-61.91 [-104.73; -19.10], p=0.01). In cross-sectional analyses at age 8 y, no associations were found between either serum or salivary cortisol and birth weight-SDS, SGA-status, or growth from birth to 6 mo. corrected age. In children born preterm, poor intrauterine and postnatal growth were associated with lower cortisol in early infancy, but not at age 8 y. Even though HPA-axis activity no longer

  17. Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe epilepsy.

    Science.gov (United States)

    Paradisi, M; Fernández, M; Del Vecchio, G; Lizzo, G; Marucci, G; Giulioni, M; Pozzati, E; Antonelli, T; Lanzoni, G; Bagnara, G P; Giardino, L; Calzà, L

    2010-10-01

    Neurogenesis in adult humans occurs in at least two areas of the brain, the subventricular zone of the telencephalon and the subgranular layer of the dentate gyrus in the hippocampal formation. We studied dentate gyrus subgranular layer neurogenesis in patients subjected to tailored antero-mesial temporal resection including amygdalohippocampectomy due to pharmacoresistant temporal lobe epilepsy (TLE) using the in vitro neurosphere assay. Sixteen patients were enrolled in the study; mesial temporal sclerosis (MTS) was present in eight patients. Neurogenesis was investigated by ex vivo neurosphere expansion in the presence of mitogens (epidermal growth factor + basic fibroblast growth factor) and spontaneous differentiation after mitogen withdrawal. Growth factor synthesis was investigated by qRT-PCR in neurospheres. We demonstrate that in vitro proliferation of cells derived from dentate gyrus of TLE patients is dependent on disease duration. Moreover, the presence of MTS impairs proliferation. As long as in vitro proliferation occurs, neurogenesis is maintained, and cells expressing a mature neurone phenotype (TuJ1, MAP2, GAD) are spontaneously formed after mitogen withdrawal. Finally, formed neurospheres express mRNAs encoding for growth (vascular endothelial growth factor) as well as neurotrophic factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor). We demonstrated that residual neurogenesis in the subgranular layer of the dentate gyrus in TLE is dependent on diseases duration and absent in MTS. © 2010 The Authors. Neuropathology and Applied Neurobiology © 2010 British Neuropathological Society.

  18. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    Directory of Open Access Journals (Sweden)

    Wei Ling Lim

    2016-08-01

    Full Text Available Maternal dexamethasone (DEX; a glucocorticoid receptor agonist exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP under the control of GnRH promoter. Pregnant females were administered with DEX (0.1mg/kg or vehicle (VEH, water daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0 males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the post synaptic marker molecule, post-synaptic density 95 was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

  19. Food, growth and time: Elsie Widdowson's and Robert McCance's research into prenatal and early postnatal growth.

    Science.gov (United States)

    Buklijas, Tatjana

    2014-09-01

    Cambridge scientists Robert McCance and Elsie Widdowson are best known for their work on the British food tables and wartime food rations, but it is their research on prenatal and early postnatal growth that is today seen as a foundation of the fields studying the impact of environment upon prenatal development and, consequently, adult disease. In this essay I situate McCance's and Widdowson's 1940s human and 1950s experimental studies in the context of pre-war concerns with fetal growth and development, especially within biochemistry, physiology and agriculture; and the Second World War and post-war focus on the effects of undernutrition during pregnancy upon the fetus. I relate Widdowson's and McCance's research on the long-term effects of early undernutrition to the concern with recovery from early trauma so pertinent in post-war Europe and with sensitive (critical) periods, a concept of high importance across different fields. Finally I discuss how, following a hiatus in which fetal physiology engaged with different questions and stressed fetal autonomy, interest in the impact of environment upon prenatal growth and development revived towards the end of the twentieth century. The new field of "developmental origins of health and disease", I suggest, has provided a context in which Widdowson's and McCance's work has regained importance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Progranulin regulates neurogenesis in the developing vertebrate retina.

    Science.gov (United States)

    Walsh, Caroline E; Hitchcock, Peter F

    2017-09-01

    We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed-retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn-a knockdown. Depleting Pgrn-a results in a significant lengthening of the cell cycle. These data suggest that Pgrn-a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn-a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 77: 1114-1129, 2017. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc.

  1. Perinatal Exposure to Glufosinate Ammonium Herbicide Impairs Neurogenesis and Neuroblast Migration through Cytoskeleton Destabilization.

    Science.gov (United States)

    Herzine, Ameziane; Laugeray, Anthony; Feat, Justyne; Menuet, Arnaud; Quesniaux, Valérie; Richard, Olivier; Pichon, Jacques; Montécot-Dubourg, Céline; Perche, Olivier; Mortaud, Stéphane

    2016-01-01

    Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ). During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA), leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray et al., 2014). Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life.

  2. Quality of life, postnatal depression and baby gender.

    Science.gov (United States)

    de Tychey, Claude; Briançon, Serge; Lighezzolo, Joëlle; Spitz, Elisabeth; Kabuth, Bernard; de Luigi, Valerie; Messembourg, Catherine; Girvan, Françoise; Rosati, Aurore; Thockler, Audrey; Vincent, Stephanie

    2008-02-01

    To study the impact of postnatal depression on the quality of life of young French mothers and to evaluate if the gender of their child influences this. Postnatal depression (PND) constitutes a major public health problem considering its high prevalence and consequences upon quality of life and parental skills. This research is a cross-sectional study during the postnatal period. This study was carried out during a two-month period. Data were collected by interview and questionnaires. The authors compared the prevalence rate of PND and life quality in a cohort of 181 women and measured the short-term impact of the child's birth. Postnatal depression strongly negatively influences all dimensions of life quality explored through the SF36, e.g. physical functioning (PF), physical Role (RP), bodily pain (BP), mental health (MH), emotional role (RE), social functioning (SF), vitality (VT), general health (GH), standardized physical component (PCS) and standardized mental component (MCS). The baby's gender (having a boy) also significantly reduces quality of life, irrespective of depressive state. There is a relationship between baby gender and PND. This research is the first to show that the birth of a boy reduces several dimensions of the mothers' quality of life. The importance of the impairment of quality of life in case of PND, as well as its effects on mother-child interaction, could justify prevention programs and early psychotherapeutic care. Further research needs to explore the effectiveness of programmes targeting the construction of parenting skills as a preventative measure against PND, especially for parents of boys.

  3. Association between maternal depressive symptoms in the early post-natal period and responsiveness in feeding at child age 2 years.

    Science.gov (United States)

    Mallan, Kimberley M; Daniels, Lynne A; Wilson, Jacinda L; Jansen, Elena; Nicholson, Jan M

    2015-10-01

    Maternal depression is a known risk factor for poor outcomes for children. Pathways to these poor outcomes relate to reduced maternal responsiveness or sensitivity to the child. Impaired responsiveness potentially impacts the feeding relationship and thus may be a risk factor for inappropriate feeding practices. The aim of this study was to examine the longitudinal relationships between self-reported maternal post-natal depressive symptoms at child age 4 months and feeding practices at child age 2 years in a community sample. Participants were Australian first-time mothers allocated to the control group of the NOURISH randomized controlled trial when infants were 4 months old. Complete data from 211 mothers (of 346 allocated) followed up when their children were 2 years of age (51% girls) were available for analysis. The relationship between Edinburgh Postnatal Depression Scale (EPDS) score (child age 4 months) and child feeding practices (child age 2 years) was tested using hierarchical linear regression analysis adjusted for maternal and child characteristics. Higher EPDS score was associated with less responsive feeding practices at child age 2 years: greater pressure [β = 0.18, 95% confidence interval (CI): 0.04-0.32, P = 0.01], restriction (β = 0.14, 95% CI: 0.001-0.28, P = 0.05), instrumental (β = 0.14, 95% CI: 0.005-0.27, P = 0.04) and emotional (β = 0.15, 95% CI: 0.01-0.29, P = 0.03) feeding practices (ΔR(2) values: 0.02-0.03, P responsiveness in child feeding. These findings suggest that the provision of support to mothers experiencing some levels of depressive symptomatology in the early post-natal period may improve responsiveness in the child feeding relationship. © 2014 John Wiley & Sons Ltd.

  4. Polysaccharides from Wolfberry Prevents Corticosterone-Induced Inhibition of Sexual Behavior and Increases Neurogenesis

    Science.gov (United States)

    Lau, Benson Wui-Man; Lee, Jada Chia-Di; Li, Yue; Fung, Sophia Man-Yuk; Sang, Yan-Hua; Shen, Jiangang; Chang, Raymond Chuen-Chung; So, Kwok-Fai

    2012-01-01

    Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of infertility and sexual dysfunction. However, there is still a scarcity of experimental evidence to support the pro-sexual effect of wolfberry. The aim of this study is to determine the effect of Lycium barbarum polysaccharides (LBP) on male sexual behavior of rats. Here we report that oral feeding of LBP for 21 days significantly improved the male copulatory performance including increase of copulatory efficiency, increase of ejaculation frequency and shortening of ejaculation latency. Furthermore, sexual inhibition caused by chronic corticosterone was prevented by LBP. Simultaneously, corticosterone suppressed neurogenesis in subventricular zone and hippocampus in adult rats, which could be reversed by LBP. The neurogenic effect of LBP was also shown in vitro. Significant correlation was found between neurogenesis and sexual performance, suggesting that the newborn neurons are associated with reproductive successfulness. Blocking neurogenesis in male rats abolished the pro-sexual effect of LBP. Taken together, these results demonstrate the pro-sexual effect of LBP on normal and sexually-inhibited rats, and LBP may modulate sexual behavior by regulating neurogenesis. PMID:22523540

  5. A longitudinal study on the maternal–fetal relationship and postnatal maternal sensitivity

    NARCIS (Netherlands)

    Maas, A.J.B.M.; de Cock, E.S.A.; Vreeswijk, C.M.J.M.; Vingerhoets, A.J.J.M.; van Bakel, H.J.A.

    2016-01-01

    Objective: The present study examined whether early signs of maternal sensitivity can be detected during pregnancy by focusing on the maternal–fetal relationship and postnatal maternal sensitivity. Background: Earlier research has identified maternal sensitive behaviour as an important factor for

  6. Antenatal interpersonal sensitivity is more strongly associated than perinatal depressive symptoms with postnatal mother-infant interaction quality.

    Science.gov (United States)

    Raine, Karen; Cockshaw, Wendell; Boyce, Philip; Thorpe, Karen

    2016-10-01

    Maternal mental health has enduring effects on children's life chances and is a substantial cost driver for child health, education and social services. A key linking mechanism is the quality of mother-infant interaction. A body of work associates maternal depressive symptoms across the antenatal and postnatal (perinatal) period with less-than-optimal mother-infant interaction. Our study aims to build on previous research in the field through exploring the association of a maternal personality trait, interpersonal sensitivity, measured in early pregnancy, with subsequent mother-infant interaction quality. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine the association between antenatal interpersonal sensitivity and postnatal mother-infant interaction quality in the context of perinatal depressive symptoms. Interpersonal sensitivity was measured during early pregnancy and depressive symptoms in the antenatal year and across the first 21 months of the postnatal period. In a subsample of the ALSPAC, mother-infant interaction was measured at 12 months postnatal through a standard observation. For the subsample that had complete data at all time points (n = 706), hierarchical regression examined the contribution of interpersonal sensitivity to variance in mother-infant interaction quality. Perinatal depressive symptoms predicted little variance in mother-infant interaction. Antenatal interpersonal sensitivity explained a greater proportion of variance in mother-infant interaction quality. The personality trait, interpersonal sensitivity, measured in early pregnancy, is a more robust indicator of subsequent mother-infant-interaction quality than perinatal depressive symptoms, thus affording enhanced opportunity to identify vulnerable mother-infant relationships for targeted early intervention.

  7. The satiating hormone amylin enhances neurogenesis in the area postrema of adult rats

    Directory of Open Access Journals (Sweden)

    Claudia G. Liberini

    2016-10-01

    Full Text Available Objective: Adult neurogenesis in the subgranular zone and subventricular zone is generally accepted, but its existence in other brain areas is still controversial. Circumventricular organs, such as the area postrema (AP have recently been described as potential neurogenic niches in the adult brain. The AP is the major site of action of the satiating hormone amylin. Amylin has been shown to promote the formation of neuronal projections originating from the AP in neonatal rodents but the role of amylin in adult neurogenesis remains unknown. Methods: To test this, we first performed an RNA-sequencing of the AP of adult rats acutely injected with either amylin (20 μg/kg, amylin plus the amylin receptor antagonist AC187 (500 μg/kg or vehicle. Second, animals were subcutaneously equipped with minipumps releasing either amylin (50 μg/kg/day or vehicle for 3 weeks to assess cell proliferation and differentiation with the 5′-bromo-2-deoxyuridine (BrdU technique. Results: Acute amylin injections affected genes involved in pathways and processes that control adult neurogenesis. Amylin consistently upregulated NeuroD1 transcript and protein in the adult AP, and this effect was blocked by the co-administration of AC187. Further, chronic amylin treatment increased the number of newly proliferated AP-cells and significantly promoted their differentiation into neurons rather than astrocytes. Conclusion: Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats. Keywords: Amylin, Adult neurogenesis, Area postrema, BrdU, Circumventricular organs

  8. Postnatal cocaine exposure: effects on behavior of rats in forced swim test.

    Science.gov (United States)

    Magalhães, Ana; Tavares, Maria Amélia; de Sousa, Liliana

    2002-06-01

    Exposure to cocaine in early periods of postnatal life has adverse effects on behavior, namely, it induces the display of anxiety and fear-like behaviors that are associated with stress and depression. This study examined the effects of early developmental cocaine exposure in several categories of behavior observed in forced swim test. Male and female Wistar rats were given 15 mg/kg of cocaine hydrochloride/body weight/day, subcutaneously, in two daily doses, from postnatal day (PND) 1 to PND27. Controls were saline injected in the same protocol. In PND26-PND27, rats were placed in a swimming pool during 5 min in two sessions. The categories of behavior studied in this work included horizontal and vertical rotation, vibrissae clean, head clean, fast and slow swim, struggling, floating, sliding, diving, head-diving, and wagging head. Results showed differences in the frequencies of several behavioral categories that allowed the discrimination of the behaviors that may constitute "behavioral despair" indicators, as well as which behaviors are most affected by cocaine exposure. Cocaine groups were less active and more immobile than controls. These results suggest that postnatal exposure to cocaine can produce depression-like effects and affect the ability of these animals to cope with stress situations.

  9. Myocardial phospholipid remodeling under different types of load imposed during early postnatal development

    Czech Academy of Sciences Publication Activity Database

    Novák, F.; Kolář, František; Hamplová, B.; Mrnka, L.; Pelouch, Václav; Ošťádal, Bohuslav; Nováková, O.

    2009-01-01

    Roč. 58, Suppl.2 (2009), S13-S32 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : phospholipids * myocardium * postnatal development Subject RIV: CE - Biochemistry Impact factor: 1.430, year: 2009

  10. Interaction Effect of Social Isolation and High Dose Corticosteroid on Neurogenesis and Emotional Behavior.

    Science.gov (United States)

    Chan, Jackie N-M; Lee, Jada C-D; Lee, Sylvia S P; Hui, Katy K Y; Chan, Alan H L; Fung, Timothy K-H; Sánchez-Vidaña, Dalinda I; Lau, Benson W-M; Ngai, Shirley P-C

    2017-01-01

    Hypercortisolemia is one of the clinical features found in depressed patients. This clinical feature has been mimicked in animal studies via application of exogenous corticosterone (CORT). Previous studies suggested that CORT can induce behavioral disturbance in anxious-depressive like behavior, which is associated with suppressed neurogenesis. Hippocampal neurogenesis plays an important role in adult cognitive and behavioral regulation. Its suppression may thus lead to neuropsychiatric disorders. Similar to the effects of CORT on the animals' depression-like behaviors and neurogenesis, social deprivation has been regarded as one factor that predicts poor prognosis in depression. Furthermore, social isolation is regarded as a stressor to social animals including experimental rodents. Hence, this study aims to examine if social isolation would induce further emotional or anxiety-like behavior disturbance and suppress neurogenesis in an experimental model that was repeatedly treated with CORT. Sprague-Dawley rats were used in this study to determine the effects of different housing conditions, either social isolated or group housing, in vehicle-treated control and CORT-treated animals. Forced swimming test (FST), open field test (OFT) and social interaction test (SIT) were used to assess depression-like, anxiety-like and social behaviors respectively. Immunohistochemistry was performed to quantify the number of proliferative cells and immature neurons in the hippocampus, while dendritic maturation of immature neurons was analyzed by Sholl analysis. Social isolation reduced latency to immobility in FST. Furthermore, social isolation could significantly reduce the ratio of doublecortin and bromodeoxyuridine (BrdU) positive cells of the neurogenesis assay under CORT-treated condition. The current findings suggested that the behavioral and neurological effect of social isolation is dependent on the condition of hypercortisolemia. Furthermore, social isolation may

  11. [Brain repair after ischemic stroke: role of neurotransmitters in post-ischemic neurogenesis].

    Science.gov (United States)

    Sánchez-Mendoza, Eduardo; Bellver-Landete, Víctor; González, María Pilar; Merino, José Joaquín; Martínez-Murillo, Ricardo; Oset-Gasque, María Jesús

    2012-11-01

    Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

  12. NR2B subunit-dependent long-term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life.

    Science.gov (United States)

    Hogsden, Jennifer L; Dringenberg, Hans C

    2009-08-01

    The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

  13. Early postnatal development of the mandible in children with isolated cleft palate and children with nonsyndromic Robin sequence

    DEFF Research Database (Denmark)

    Eriksen, J.; Hermann, N.V.; Darvann, Tron Andre

    2006-01-01

    Objective: Analysis of early postnatal mandibular size and growth velocity in children with untreated isolated cleft palate (ICP), nonsyndromic Robin sequence (RS), and a control group of children with unilateral incomplete cleft lip (UICL). Material: 114 children (66 isolated cleft palate, 7 Robin...... and mandibular growth velocity (mm/year) was calculated. Cleft width was measured on the casts at 2 months of age. Results: Mean mandibular length and posterior height were significantly smaller in isolated cleft palate and Robin sequence, compared with unilateral incomplete cleft lip. Mandibular length in Robin...... sequence was also significantly shorter, compared with isolated cleft palate. No significant difference was found between mean mandibular growth velocities in the three groups. No significant correlation was found between mandibular length and cleft width in either isolated cleft palate or Robin sequence...

  14. Hippocampal neurogenesis in the C57BL/6J mice at early adulthood following prenatal alcohol exposure.

    Science.gov (United States)

    Olateju, Oladiran I; Spocter, Muhammad A; Patzke, Nina; Ihunwo, Amadi O; Manger, Paul R

    2018-04-01

    We examined the effect of chronic prenatal alcohol exposure (PAE) on the process of adult neurogenesis in C57BL/6J mice at early adulthood (PND 56). Pregnant mice, and their in utero litters, were exposed to alcohol, through oral gavage, on gestational days 7-16, with recorded blood alcohol concentrations averaging 184 mg/dL (CA group). Two control groups, sucrose (CAc) and non-treated (NTc) control groups were also examined. The brains of pups at PND 56 from each experimental group were sectioned in a sagittal plane, and stained for Nissl substance with cresyl violet, and immunostained for Ki-67 which labels proliferative cells and doublecortin (DCX) for immature neurons. Morphologically, the neurogenic pattern was identical in all three groups studied. Populations of Ki-67 immunopositive cells in the dentate gyrus were not statistically significantly different between the experimental groups and there were no differences between the sexes. Thus, the PAE in this study does not appear to have a strong effect on the proliferative process in the adult hippocampus. In contrast, the numbers of immature neurons, labeled with DCX, was statistically significantly lower in the prenatal alcohol exposed mice compared with the two control groups. Alcohol significantly lowered the number of DCX hippocampal cells in the male mice, but not in the female mice. This indicates that the PAE appears to lower the rate of conversion of proliferative cells to immature neurons and this effect of alcohol is sexually dimorphic. This lowered number of immature neurons in the hippocampus appears to mirror hippocampal dysfunctions observed in FASD children.

  15. The Effects of Maternal Postnatal Depression and Child Sex on Academic Performance at Age 16 Years: A Developmental Approach

    Science.gov (United States)

    Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Croudace, Tim; Cooper, Peter

    2010-01-01

    Background: Postnatal depression (PND) is associated with poor cognitive functioning in infancy and the early school years; long-term effects on academic outcome are not known. Method: Children of postnatally depressed (N = 50) and non-depressed mothers (N = 39), studied from infancy, were followed up at 16 years. We examined the effects on…

  16. Understanding exercise self-efficacy and barriers to leisure-time physical activity among postnatal women.

    Science.gov (United States)

    Cramp, Anita G; Bray, Steven R

    2011-07-01

    Studies have demonstrated that postnatal women are at high risk for physical inactivity and generally show lower levels of leisure-time physical activity (LTPA) compared to prepregnancy. The overall purpose of the current study was to investigate social cognitive correlates of LTPA among postnatal women during a 6-month period following childbirth. A total of 230 women (mean age = 30.9) provided descriptive data regarding barriers to LTPA and completed measures of LTPA and self-efficacy (exercise and barrier) for at least one of the study data collection periods. A total of 1,520 barriers were content analyzed. Both exercise and barrier self-efficacy were positively associated with subsequent LTPA. Exercise self-efficacy at postnatal week 12 predicted LTPA from postnatal weeks 12 to 18 (β = .40, R (2) = .18) and exercise self-efficacy at postnatal week 24 predicted LTPA during weeks 24-30 (β = .49, R (2) = .30). Barrier self-efficacy at week 18 predicted LTPA from weeks 18 to 24 (β = .33, R (2) = .13). The results of the study identify a number of barriers to LTPA at multiple time points closely following childbirth which may hinder initiation, resumption or maintenance of LTPA. The results also suggest that higher levels of exercise and barrier self-efficacy are prospectively associated with higher levels of LTPA in the early postnatal period. Future interventions should be designed to investigate causal effects of developing participants' exercise and barrier self-efficacy for promoting and maintaining LTPA during the postnatal period.

  17. Neuronal Rac1 Is Required for Learning-Evoked Neurogenesis

    Science.gov (United States)

    Anderson, Matthew P.; Freewoman, Julia; Cord, Branden; Babu, Harish; Brakebusch, Cord

    2013-01-01

    Hippocampus-dependent learning and memory relies on synaptic plasticity as well as network adaptations provided by the addition of adult-born neurons. We have previously shown that activity-induced intracellular signaling through the Rho family small GTPase Rac1 is necessary in forebrain projection neurons for normal synaptic plasticity in vivo, and here we show that selective loss of neuronal Rac1 also impairs the learning-evoked increase in neurogenesis in the adult mouse hippocampus. Earlier work has indicated that experience elevates the abundance of adult-born neurons in the hippocampus primarily by enhancing the survival of neurons produced just before the learning event. Loss of Rac1 in mature projection neurons did reduce learning-evoked neurogenesis but, contrary to our expectations, these effects were not mediated by altering the survival of young neurons in the hippocampus. Instead, loss of neuronal Rac1 activation selectively impaired a learning-evoked increase in the proliferation and accumulation of neural precursors generated during the learning event itself. This indicates that experience-induced alterations in neurogenesis can be mechanistically resolved into two effects: (1) the well documented but Rac1-independent signaling cascade that enhances the survival of young postmitotic neurons; and (2) a previously unrecognized Rac1-dependent signaling cascade that stimulates the proliferative production and retention of new neurons generated during learning itself. PMID:23884931

  18. Immune Regulator MCPIP1 Modulates TET Expression during Early Neocortical Development

    Directory of Open Access Journals (Sweden)

    Huihui Jiang

    2016-09-01

    Full Text Available MCPIP1 is a recently identified immune regulator that plays critical roles in preventing immune disorders, and is also present in the brain. Currently an unresolved question remains as to how MCPIP1 performs its non-immune functions in normal brain development. Here, we report that MCPIP1 is abundant in neural progenitor cells (NPCs and newborn neurons during the early stages of neurogenesis. The suppression of MCPIP1 expression impairs normal neuronal differentiation, cell-cycle exit, and concomitant NPC proliferation. MCPIP1 is important for maintenance of the NPC pool. Notably, we demonstrate that MCPIP1 reduces TET (TET1/TET2/TET3 levels and then decreases 5-hydroxymethylcytosine levels. Furthermore, the MCPIP1 interaction with TETs is involved in neurogenesis and in establishing the proper number of NPCs in vivo. Collectively, our findings not only demonstrate that MCPIP1 plays an important role in early cortical neurogenesis but also reveal an unexpected link between neocortical development, immune regulators, and epigenetic modification.

  19. Neurogenesis Inhibition Prevents Enriched Environment to Prolong and Strengthen Social Recognition Memory, But Not to Increase BDNF Expression.

    Science.gov (United States)

    Pereira-Caixeta, Ana Raquel; Guarnieri, Leonardo O; Pena, Roberta R; Dias, Thomáz L; Pereira, Grace Schenatto

    2017-07-01

    Hippocampus-dependent memories, such as social recognition (SRM), are modulated by neurogenesis. However, the precise role of newborn neurons in social memory processing is still unknown. We showed previously that 1 week of enriched environment (EE) is sufficient to increase neurogenesis in the hippocampus (HIP) and the olfactory bulb (OB) of mice. Here, we tested the hypothesis that 1 week of EE would enhance SRM persistence and strength. In addition, as brain-derived neurotrophic factor (BDNF) may mediate some of the neurogenesis effects on memory, we also tested if 1 week of EE would increase BDNF expression in the HIP and OB. We also predicted that neurogenesis inhibition would block the gain of function caused by EE on both SRM and BDNF expression. We found that EE increased BDNF expression in the HIP and OB of mice; at the same time, it allowed SRM to last longer. In addition, mice on EE had their SRM unaffected by memory consolidation interferences. As we predicted, treatment with the anti-mitotic drug AraC blocked EE effects on SRM. Surprisingly, neurogenesis inhibition did not affect the BDNF expression, increased by EE. Together, our results suggest that newborn neurons improve SRM persistence through a BDNF-independent mechanism. Interestingly, this study on social memory uncovered an unexpected dissociation between the effect of adult neurogenesis and BDNF expression on memory persistence, reassuring the idea that not all neurogenesis effects on memory are BDNF-dependent.

  20. Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M.; Xu, Lihong; Storm, Daniel R.

    2015-01-01

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. PMID:25995470

  1. Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain.

    Science.gov (United States)

    Nokia, Miriam S; Anderson, Megan L; Shors, Tracey J

    2012-12-01

    Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood-brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3-12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesised that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague-Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta-band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the 'chemobrain'. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  2. Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

    Directory of Open Access Journals (Sweden)

    Fabio Cavaliere

    2016-01-01

    Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

  3. Pre- and postnatal stress and asthma in children: Temporal- and sex-specific associations

    Science.gov (United States)

    Lee, Alison; Chiu, Yueh-Hsiu Mathilda; Rosa, Maria José; Jara, Calvin; Wright, Robert O.; Coull, Brent A.; Wright, Rosalind J.

    2016-01-01

    BACKGROUND Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. OBJECTIVES We examined associations between pre- and/or postnatal stress and children's asthma (n=765) and effect modification by sex in a prospective cohort study. METHODS Maternal negative life events (NLEs) were ascertained prenatally and postpartum. NLEs scores were categorized as 0, 1-2, 3-4, or ≥5 to assess exposure-response relationships. We examined effects of pre- and postnatal stress on children's asthma by age 6 years modeling each as independent predictors; mutually adjusting for prenatal and postnatal stress; and finally considering interactions between pre- and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. RESULTS When considering stress in each period independently, among boys a dose-response relationship was evident for each level increase on the ordinal scale prenatally (OR=1.38, 95% CI 1.06, 1.79; p-for-trend=0.03) and postnatally (OR=1.53, 95% CI 1.16, 2.01; p-for-trend=0.001); among girls only the postnatal trend was significant (OR=1.60, 95% CI 1.14, 2.22; p-for-trend=0.005). Higher stress in both the pre- and postnatal periods was associated with increased odds of being diagnosed with asthma in girls [OR=1.37, 95% CI 0.98, 1.91 (pinteraction=0.07)] but not boys [OR=1.08, 95% CI 0.82, 1.42 (pinteraction=0.61)]. CONCLUSIONS While boys were more vulnerable to stress during the prenatal period, girls were more impacted by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early life stress may provide unique insight into asthma etiology and natural history. PMID:26953156

  4. Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats.

    Science.gov (United States)

    Sofronova, Svetlana I; Gaynullina, Dina K; Shvetsova, Anastasia A; Borzykh, Anna A; Selivanova, Ekaterina K; Kostyunina, Daria S; Sharova, Anna P; Martyanov, Andrey A; Tarasova, Olga S

    2017-11-01

    The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α 1 -adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. © 2017 Society for Endocrinology.

  5. Extremely weak magnetic field exposure may inhibit hippocampal neurogenesis of Sprague Dawley rats

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    Zhang, B.; Tian, L.; Cai, Y.; Xu, H.; Pan, Y.

    2016-12-01

    Hippocampal neurogenesis occurs throughout life in mammals brains and can be influenced by animals' age as well as environmental factors. Lines of evidences have shown that the magnetic field is an important physics environmental factor influencing many animals' growth and development, and extremely weak magnetic field exposures have been proved having serious adverse effects on the metabolism and behaviors in some animals, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we experimentally examined the extremely weak magnetic field effects on neurogenesis of the dentate gyrus (DG) of hippocampus of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, an extremely weak magnetic field (≤ 0.5μT) and the geomagnetic fields (strength 31-58μT) as controls. Thirty-two SD rats (3-weeks old) were used in this study. New cell survival in hippocampus was assessed at 0, 14, 28, and 42 days after a 7-day intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Meanwhile, the amounts of immature neurons and mature neurons which are both related to hippocampal neurogenesis, as documented by labeling with doublecortin (DCX) and neuron (NeuN), respectively, were also analyzed at 0, 14, 28, and 42 days. Compared with geomagnetic field exposure groups, numbers of BrdU-, DCX-positive cells of DG of hippocampus in tested rats reduces monotonously and more rapidly after 14 days, and NeuN-positive cells significantly decreases after 28days when exposed in the extremely weak magnetic field condition. Our data suggest that the exposure to an extremely weak magnetic field may suppress the neurogenesis in DG of SD rats.

  6. Contribution of constitutively proliferating precursor cell subtypes to dentate neurogenesis after cortical infarcts

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    Oberland Julia

    2010-11-01

    Full Text Available Abstract Background It is well known that focal ischemia increases neurogenesis in the adult dentate gyrus of the hippocampal formation but the cellular mechanisms underlying this proliferative response are only poorly understood. We here investigated whether precursor cells which constitutively proliferate before the ischemic infarct contribute to post-ischemic neurogenesis. To this purpose, transgenic mice expressing green fluorescent protein (GFP under the control of the nestin promoter received repetitive injections of the proliferation marker bromodeoxyuridine (BrdU prior to induction of cortical infarcts. We then immunocytochemically analyzed the fate of these BrdU-positive precursor cell subtypes from day 4 to day 28 after the lesion. Results Quantification of BrdU-expressing precursor cell populations revealed no alteration in number of radial glia-like type 1 cells but a sequential increase of later precursor cell subtypes in lesioned animals (type 2a cells at day 7, type 3 cells/immature neurons at day 14. These alterations result in an enhanced survival of mature neurons 4 weeks postinfarct. Conclusions Focal cortical infarcts recruit dentate precursor cells generated already before the infarct and significantly contribute to an enhanced neurogenesis. Our findings thereby increase our understanding of the complex cellular mechanisms of postlesional neurogenesis.

  7. A weak magnetic field inhibits hippocampal neurogenesis in SD rats

    Science.gov (United States)

    Zhang, B.; Tian, L.; Cai, Y.; Pan, Y.

    2017-12-01

    Geomagnetic field is an important barrier that protects life forms on Earth from solar wind and radiation. Paleomagnetic data have well demonstrated that the strength of ancient geomagnetic field was dramatically weakened during a polarity transition. Accumulating evidence has shown that weak magnetic field exposures has serious adverse effects on the metabolism and behaviors in organisms. Hippocampal neurogenesis occurs throughout life in mammals' brains which plays a key role in brain function, and can be influenced by animals' age as well as environmental factors, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we have investigated the weak magnetic field effects on hippocampal neurogenesis of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, a weak magnetic field (≤1.3 μT) and the geomagnetic fields (51 μT).The latter is treated as a control condition. SD rats were exposure to the weak magnetic field up to 6 weeks. We measured the changes of newborn nerve cells' proliferation and survival, immature neurons, neurons and apoptosis in the dentate gyrus (DG) of hippocampus in SD rats. Results showed that, the weak magnetic field (≤1.3 μT) inhibited their neural stem cells proliferation and significantly reduced the survival of newborn nerve cells, immature neurons and neurons after 2 or 4 weeks continuous treatment (i.e. exposure to weak magnetic field). Moreover, apoptosis tests indicated the weak magnetic field can promote apoptosis of nerve cells in the hippocampus after 4 weeks treatment. Together, our new data indicate that weak magnetic field decrease adult hippocampal neurogenesis through inhibiting neural stem cells proliferation and promoting apoptosis, which provides useful experimental constraints on better understanding the mechanism of linkage between life and geomagnetic field.

  8. Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

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    Müller Anke

    2010-06-01

    Full Text Available Abstract Background Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Δ9-tetrahydrocannabinol (THC and Cannabidiol (CBD fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1 deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail. Results THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX-expressing intermediate progenitor cells. Conclusion CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.

  9. Pre- and postnatal nutrition in sheep affects ß-cell secretion and hypothalamic control

    DEFF Research Database (Denmark)

    Kongsted, Anna Hauntoft; Husted, Sanne Vinter; Thygesen, Malin P.

    2013-01-01

    Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose–insulin axis are not readily detectable by conventional tests early in life, making...... and short-term abundance of food. In this study, twin-pregnant sheep were fed diets meeting 100% (NORM) or 50% (LOW) of energy and protein requirements during the last trimester. Twin offspring were fed either a normal moderate (CONV) diet or a high-carbohydrate–high-fat (HCHF) diet from 3 days to 6 months...... abundance) and adrenalin challenges. At 6 months of age, postnatal HCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutrition was found to be associated with unexpected endocrine responses...

  10. Changes in ultrastructure of rat ovaries after early postnatal x-ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, A [Juntendo Univ., Tokyo (Japan). School of Medicine

    1975-02-01

    Female rats were irradiated with 190R of X-rays at 10 days of age and the ovarian ultrastructures were studied 4 and 7 months after irradiation. Ultrastructural changes were found in germinal epithelial cells, in fibroblasts in the tunica albuginea and in interstitial cells. The germinal epithelial cells exhibited various signs of degeneration but no sign of proliferation. Electron density of their basal part was reduced considerably. Their mitochondria became swollen and free ribosomes were decreased in number. The nuclei often protruded from the free surface of these cells. These cells frequently fragmented and, finally, complete desquamation occurred. The basement membrane became unevently thickened. Nuclei of enlarged fibroblasts in the tunica albuginea became irregularly ellipsoid in shape, and the nuclear envelope was occasionally invaginated. Various cytoplasmic organelles of the fibroblasts were well-developed. Some abnormal invasion of cytoplasm into the nucleus was found in the interstitial cells showing the ultrastructural characteristics of steroid hormone synthesis. Various cytoplasmic roganelles and inclusions invaded into the nuclei of these cells and the nuclear envelope sometimes disappeared locally. These interstitial cells contained a large number of irregular-shaped electron dense mitochondria with vesicular cristae, and numerous dilated vesicles of smooth-surfaced endoplasmic reticulum (SER). The cells of the anovular follicles in the irradiated ovaries resembled, in fine structure, the granulosa cells in normal primary follicles of non-irradiated ovaries. These cells seemed to be less affected by early postnatal irradiation.

  11. Impaired neurogenesis of the dentate gyrus is associated with pattern separation deficits: A computational study.

    Science.gov (United States)

    Faghihi, Faramarz; Moustafa, Ahmed A

    2016-09-01

    The separation of input patterns received from the entorhinal cortex (EC) by the dentate gyrus (DG) is a well-known critical step of information processing in the hippocampus. Although the role of interneurons in separation pattern efficiency of the DG has been theoretically known, the balance of neurogenesis of excitatory neurons and interneurons as well as its potential role in information processing in the DG is not fully understood. In this work, we study separation efficiency of the DG for different rates of neurogenesis of interneurons and excitatory neurons using a novel computational model in which we assume an increase in the synaptic efficacy between excitatory neurons and interneurons and then its decay over time. Information processing in the EC and DG was simulated as information flow in a two layer feed-forward neural network. The neurogenesis rate was modeled as the percentage of new born neurons added to the neuronal population in each time bin. The results show an important role of an optimal neurogenesis rate of interneurons and excitatory neurons in the DG in efficient separation of inputs from the EC in pattern separation tasks. The model predicts that any deviation of the optimal values of neurogenesis rates leads to different decreased levels of the separation deficits of the DG which influences its function to encode memory.

  12. TLX-Its Emerging Role for Neurogenesis in Health and Disease.

    Science.gov (United States)

    Sobhan, Praveen K; Funa, Keiko

    2017-01-01

    The orphan nuclear receptor TLX, also called NR2E1, is a factor important in the regulation of neural stem cell (NSC) self-renewal, neurogenesis, and maintenance. As a transcription factor, TLX is vital for the expression of genes implicated in neurogenesis, such as DNA replication, cell cycle, adhesion and migration. It acts by way of repressing or activating target genes, as well as controlling protein-protein interactions. Growing evidence suggests that dysregulated TLX acts in the initiation and progression of human disorders of the nervous system. This review describes recent knowledge about TLX expression, structure, targets, and biological functions, relevant to maintaining adult neural stem cells related to both neuropsychiatric conditions and certain nervous system tumours.

  13. Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model.

    Science.gov (United States)

    Murai, Kiyohito; Qu, Qiuhao; Sun, GuoQiang; Ye, Peng; Li, Wendong; Asuelime, Grace; Sun, Emily; Tsai, Guochuan E; Shi, Yanhong

    2014-06-24

    The role of the nuclear receptor TLX in hippocampal neurogenesis and cognition has just begun to be explored. In this study, we generated a transgenic mouse model that expresses TLX under the control of the promoter of nestin, a neural precursor marker. Transgenic TLX expression led to mice with enlarged brains with an elongated hippocampal dentate gyrus and increased numbers of newborn neurons. Specific expression of TLX in adult hippocampal dentate gyrus via lentiviral transduction increased the numbers of BrdU(+) cells and BrdU(+)NeuN(+) neurons. Furthermore, the neural precursor-specific expression of the TLX transgene substantially rescued the neurogenic defects of TLX-null mice. Consistent with increased neurogenesis in the hippocampus, the TLX transgenic mice exhibited enhanced cognition with increased learning and memory. These results suggest a strong association between hippocampal neurogenesis and cognition, as well as significant contributions of TLX to hippocampal neurogenesis, learning, and memory.

  14. Imaging and recording subventricular zone progenitor cells in live tissue of postnatal mice

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    Benjamin Lacar

    2010-07-01

    Full Text Available The subventricular zone (SVZ is one of two regions where neurogenesis persists in the postnatal brain. The SVZ, located along the lateral ventricle, is the largest neurogenic zone in the brain that contains multiple cell populations including astrocyte-like cells and neuroblasts. Neuroblasts migrate in chains to the olfactory bulb where they differentiate into interneurons. Here, we discuss the experimental approaches to record the electrophysiology of these cells and image their migration and calcium activity in acute slices. Although these techniques were in place for studying glial cells and neurons in mature networks, the SVZ raises new challenges due to the unique properties of SVZ cells, the cellular diversity, and the architecture of the region. We emphasize different methods, such as the use of transgenic mice and in vivo electroporation that permit identification of the different SVZ cell populations for patch clamp recording or imaging. Electroporation also permits genetic labeling of cells using fluorescent reporter mice and modification of the system using either RNA interference technology or floxed mice. In this review, we aim to provide conceptual and technical details of the approaches to perform electrophysiological and imaging studies of SVZ cells.

  15. Effect of Metformin on Adult Hippocampal Neurogenesis: Comparison with Donepezil and Links to Cognition.

    Science.gov (United States)

    Ahmed, Sara; Mahmood, Zahra; Javed, Aneela; Hashmi, Shoaib Naiyer; Zerr, Inga; Zafar, Saima; Zahid, Saadia

    2017-05-01

    Recent studies have uncovered evidence suggesting that interference with hippocampal adult neurogenesis contributes to neurodegeneration in Alzheimer's disease (AD). Evidence supporting that AD is a metabolic disease with derangements in brain glucose utilization implies the use of anti-diabetics as an alternate therapeutic strategy. The present study drew comparison between the pro-neurogenic potential of metformin and donepezil in AlCl 3 -induced mouse model of neurodegeneration. Morris water maze task and subsequent immunohistochemical evaluation for NeuN was conducted. Expression of neurogenesis markers and hippocampal proteome analysis was determined by qRT-PCR and SDS-PAGE, respectively, followed by ESI-QTOFF MS/MS identification. The results demonstrated impaired spatial memory and differential expression of eight proteins in the AlCl 3 group as compared to the controls. Interestingly, treatment with metformin normalized the proteome profile and expression levels of neurogenesis markers along with improvement in the spatial memory. Moreover, as compared to donepezil, metformin-treated mice exhibited an enhanced number of post-mitotic NeuN-positive neurons. It is suggested that underlying molecular mechanisms of metformin-mediated adult hippocampal neurogenesis may have implications in treatment of neurodegenerative disorders.

  16. Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

    2015-05-20

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. Copyright © 2015 the authors 0270-6474/15/357833-17$15.00/0.

  17. NeuroD Modulates Opioid Agonist-Selective Regulation of Adult Neurogenesis and Contextual Memory Extinction

    OpenAIRE

    Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee

    2013-01-01

    Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate o...

  18. Interaction Effect of Social Isolation and High Dose Corticosteroid on Neurogenesis and Emotional Behavior

    OpenAIRE

    Chan, Jackie N.-M.; Lee, Jada C.-D.; Lee, Sylvia S. P.; Hui, Katy K. Y.; Chan, Alan H. L.; Fung, Timothy K.-H.; S?nchez-Vida?a, Dalinda I.; Lau, Benson W.-M.; Ngai, Shirley P.-C.

    2017-01-01

    Hypercortisolemia is one of the clinical features found in depressed patients. This clinical feature has been mimicked in animal studies via application of exogenous corticosterone (CORT). Previous studies suggested that CORT can induce behavioral disturbance in anxious-depressive like behavior, which is associated with suppressed neurogenesis. Hippocampal neurogenesis plays an important role in adult cognitive and behavioral regulation. Its suppression may thus lead to neuropsychiatric disor...

  19. Increase in neurogenesis and behavioural benefit after chronic fluoxetine treatment in Wistar rats

    DEFF Research Database (Denmark)

    Klein, Anders Bue; Flagstad, P; Kristjansen, P E G

    2008-01-01

    Disturbances in hippocampal neurogenesis may be involved in the pathophysiology of depression and it has been argued that an increase in the generation of new nerve cells in the hippocampus is involved in the mechanism of action of antidepressants.......Disturbances in hippocampal neurogenesis may be involved in the pathophysiology of depression and it has been argued that an increase in the generation of new nerve cells in the hippocampus is involved in the mechanism of action of antidepressants....

  20. Is the organisation and structure of hospital postnatal care a barrier to quality care? Findings from a state-wide review in Victoria, Australia.

    Science.gov (United States)

    McLachlan, Helen L; Forster, Della A; Yelland, Jane; Rayner, Joanne; Lumley, Judith

    2008-09-01

    to describe the structure and organisation of hospital postnatal care in Victoria, Australia. postal survey sent to all public hospitals in Victoria (n=71) and key-informant interviews with midwives and medical practitioners (n=38). Victoria, Australia. providers of postnatal care in Victorian public hospitals. there is significant diversity across Victoria in the way postnatal units are structured and organised and in the way care is provided. There are differences in numerous practices, including maternal and neonatal observations and the length of time women spend in hospital after giving birth. Although the benefits of continuity of care are recognised by health care providers, continuity is difficult to provide in the postnatal period. Postnatal care is provided in busy, sometimes chaotic environments, with many barriers to providing effective care and few opportunities for women to rest and recover after childbirth. The findings in this study can, in part, be explained by the lack of evidence that has been available to guide early postnatal care. current structures such as standard postnatal documentation (clinical pathways) and fixed length of stay, may inhibit rather than support individualised care for women after childbirth. There is a need to move towards greater flexibility in providing of early postnatal care, including alternative models of service delivery; choice and flexibility in the length of stay after birth; a focus on the individual with far less emphasis on care being structured around organisational requirements; and building an evidence base to guide care.

  1. Perinatal exposure to glufosinate ammonium herbicide impairs neurogenesis and neuroblast migration through cytoskeleton destabilization

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    Ameziane Herzine

    2016-08-01

    Full Text Available Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ. During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA, leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray, Herzine et al. 2014 . Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life.

  2. Juvenile social defeat stress exposure persistently impairs social behaviors and neurogenesis.

    Science.gov (United States)

    Mouri, Akihiro; Ukai, Mayu; Uchida, Mizuki; Hasegawa, Sho; Taniguchi, Masayuki; Ito, Takahiro; Hida, Hirotake; Yoshimi, Akira; Yamada, Kiyofumi; Kunimoto, Shohko; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

    2018-05-01

    Adverse juvenile experiences, including physical abuse, often have negative health consequences later in life. We investigated the influence of social defeat stress exposure as juveniles on neuropsychological behaviors, and the causal role of glucocorticoids in abnormal behaviors and impairment of neurogenesis in mice exposed to the stress. The juvenile (24-day-old) and adult (70-day-old) male C57BL/6J mice were exposed to social defeat stress induced by an aggressive ICR mouse. Social defeat stress exposure as juveniles, even for 1 day, induced persistent social avoidance to the unfamiliar ICR mouse in the social interaction test, but that was not observed in mice exposed to the stress as adults. Social avoidance by the stress exposure as juveniles for 10 consecutive days was observed, when the target mouse was not only unfamiliar ICR but also another C57BL/J mouse, but not an absent or an anesthetized ICR mouse. The stress exposure did not induce anxiety- and depression-like behaviors in spontaneous locomotor activity, elevated plus-maze test, marble-burying test, forced swimming test, or sucrose preference test. Serum corticosterone levels increased immediately after the stress exposure. The hippocampal neurogenesis was suppressed 1 day and 4 weeks after the stress exposure. Administration of mifepristone, a glucocorticoid receptor antagonist, prior to each stress exposure, blocked the persistent social avoidance and suppression of neurogenesis. In conclusion, social avoidance induced by social defeat stress exposure as juveniles are more persistent than that as adults. These social avoidances are associated with suppression of hippocampal neurogenesis via glucocorticoid receptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Effects of postnatal anoxia on striatal dopamine metabolism and prepulse inhibition in rats

    DEFF Research Database (Denmark)

    Sandager-Nielsen, Karin; Andersen, Maibritt B; Sager, Thomas N

    2004-01-01

    in schizophrenic patients. There was no effect of postnatal anoxia on either baseline or d-amphetamine-induced deficit in the prepulse inhibition (PPI) paradigm in adulthood. Accordingly, although oxygen deficiency early in life has been discussed as vulnerability factor in developing schizophrenia, exposure...

  4. Adult neurogenesis in the olfactory system shapes odor memory and perception.

    Science.gov (United States)

    Gheusi, Gilles; Lledo, Pierre-Marie

    2014-01-01

    The olfactory system is a dynamic place. In mammals, not only are sensory neurons located in the sensory organ renewed through adult life, but also its first central relay is reconstructed by continuous neuronal recruitment. Despite these numerous morphological and physiological changes, olfaction is a unique sensory modality endowed with a privileged link to memory. This raises a clear conundrum; how does the olfactory system balance its neuronal turnover with its participation in long-term memory? This review concentrates on the functional aspects of adult neurogenesis, addressing how the integration of late-born neurons participates in olfactory perception and memory. After outlining the properties of adult neurogenesis in the olfactory system, and after describing their regulation by internal and environmental factors, we ask how the process of odorant perception can be influenced by constant neuronal turnover. We then explore the possible functional roles that newborn neurons might have for olfactory memory. Throughout this review, and as we concentrate almost exclusively on mammalian models, we stress the idea that adult neurogenesis is yet another form of plasticity used by the brain to copes with a constantly changing olfactory world. © 2014 Elsevier B.V. All rights reserved.

  5. Understanding adult neurogenesis beyond its role in learning and memory formation

    Directory of Open Access Journals (Sweden)

    Ab Latif Wani

    2017-04-01

    Full Text Available There has been a shift in the understanding of brain, neurons, and their functional role over the last two decades. Earlier it was believed that the brain was a static organ and was not subject to any change throughout life. An understanding was developed later that brain reorganizes its structure by a specific property called neuroplasticity. Recent research shows that the brain generates new neurons even in the adult stage, and this process is called adult neurogenesis. Although researchers still not have all the answers about the newborn neurons, and why and how they are generated, and what is their role, some have highlighted the importance of these in learning and memory formation, and even in memories of fear and spatial navigation. A wide range of environmental experience influences the generation of newborn neurons and their functional variability. There are questions about how different environmental experiences cause the differences in the generation of new neurons. Recently the field of optogenetics attempted to answer the questions on adult neurogenesis. However there are still questions about adult neurogenesis which needs a more naturalistic approach, for their better understanding.

  6. Exposure to swainsonine impairs adult neurogenesis and spatial learning and memory.

    Science.gov (United States)

    Wang, Jiutao; Song, Lingzhen; Zhang, Qi; Zhang, Wei; An, Lei; Zhang, Yamei; Tong, Dewen; Zhao, Baoyu; Chen, Shulin; Zhao, Shanting

    2015-01-05

    Swainsonine (SW) is an indolizidine triol plant alkaloid isolated from the species Astragalus, colloquially termed locoweed. Ingestion induces severe neurological symptoms of livestock and wildlife, including ataxia, trembling, exaggerated fright reactions. Toxicity to the central and peripheral nervous system is caused by inhibition of lysosomal a-mannosidase (AMA) and accumulation of intracellular oligosaccharide. However, the effects of SW on adult neurogenesis and cognition have remained unclear. Therefore, the present study was conducted to examine the effects of SW on adult neurogenesis and learning as well as memory performance in adult mice. SW (10μg/mL in drinking water) was administered orally to mice for 4 weeks. Our results showed that SW reduced proliferation and survival of neural progenitor cells (NPCs) in culture, and in the hippocampus of adult mice. In addition, exposure to SW led to down-regulation of doublecortin (DCX) and synaptophysin (SYP) in the hippocampus. However, caspase 3 and glial fibrillary acidic protein (GFAP) levels were significantly increased in SW-treated mice. Finally, SW-treated mice exhibited deficits in hippocampus-dependent spatial learning and memory. Our findings suggest that SW affects adult neurogenesis and cognitive function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid Fatty Acid composition in a muscle type specific manner in sheep.

    Directory of Open Access Journals (Sweden)

    Lei Hou

    Full Text Available We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD and biceps femoris (BF and in the cardiac muscle (ventriculus sinister cordis (VSC of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM or 50% (LOW of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty, twin offspring received a high-carbohydrate-high-fat (HCHF or a moderate-conventional (CONV diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults. The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4 protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced

  8. A qualitative study of the acceptability of routine screening of postnatal women using the Edinburgh Postnatal Depression Scale.

    Science.gov (United States)

    Shakespeare, Judy; Blake, Fiona; Garcia, Jo

    2003-01-01

    BACKGROUND: Screening for postnatal depression using the Edinburgh Postnatal Depression Scale (EPDS) has been widely recommended and implemented in primary care, although little is known about how acceptable it is to women. AIM: To explore the acceptability to women of postnatal screening by health visitors with the EPDS. DESIGN OF STUDY: Qualitative interview study. SETTING: Postnatal patients from 22 general practices within the area of Oxford City Primary Care Group. METHOD: Thirty-nine postnatal women from a purposive sample were interviewed, chosen on the basis of different general practices, EPDS results at eight weeks and eight months postnatal, and whether 'listening visits' were received. The interviews were analysed using the constant comparative method. RESULTS: Just over half of the women interviewed found screening with the EPDS less than acceptable, whatever their postnatal emotional health. The main themes identified were problems with the process of screening and, in particular, the venue, the personal intrusion of screening and stigma. The women interviewed had a clear preference for talking about how they felt, rather than filling out a questionnaire. CONCLUSION: For this sample, routine screening with the EPDS was less than acceptable for the majority of women. This is of concern, as universal screening with the EPDS for the detection of postnatal depression is already recommended and widespread in primary care. PMID:14601337

  9. Does developmental hypothyroidism produce lasting effects on adult neurogenesis?

    Science.gov (United States)

    The subgranular zone of the dentate gyrus (DO) of the adult hippocampus generates new neurons throughout life. Thyroid hormones (TH) are essential for brain development, but impaired neurogenesis with adult hypothyroidism has also been reported. We investigated the role of milder...

  10. Perlecan controls neurogenesis in the developing telencephalon

    Directory of Open Access Journals (Sweden)

    Fairén Alfonso

    2007-04-01

    Full Text Available Abstract Background Perlecan is a proteoglycan expressed in the basal lamina of the neuroepithelium during development. Perlecan absence does not impair basal lamina assembly, although in the 55% of the mutants early disruptions of this lamina conducts to exencephaly, impairing brain development. The rest of perlecan-null brains complete its prenatal development, maintain basal lamina continuity interrupted by some isolated ectopias, and are microcephalic. Microcephaly consists of thinner cerebral walls and underdeveloped ganglionic eminences. We have studied the mechanisms that generate brain atrophy in telencephalic areas where basal lamina is intact. Results Brain atrophy in the absence of perlecan started in the ventral forebrain and extended to lateral and dorsal parts of the cortex in the following stages. First, the subpallial forebrain developed poorly in early perlecan-null embryos, because of a reduced cell proliferation: the number of cells in mitosis decreased since the early stages of development. This reduction resulted in a decreased tangential migration of interneurons to the cerebral cortex. Concomitant with the early hypoplasia observed in the medial ganglionic eminences, Sonic Hedgehog signal decreased in the perlecan-null floor plate basal lamina at E12.5. Second, neurogenesis in the pallial neuroepithelium was affected in perlecan deficient embryos. We found reductions of nearly 50% in the number of cells exiting the cell cycle at E12–E13. The labeling index, which was normal at this age, significantly decreased with advancing corticogenesis. Moreover, nestin+ or PCNA+ progenitors increased since E14.5, reaching up to about 150% of the proportion of PCNA+ cells in the wild-type at E17.5. Thus, labeling index reduction together with increased progenitor population, suggests that atrophy is the result of altered cell cycle progression in the cortical progenitors. Accordingly, less neurons populated the cortical plate and

  11. Electrophysiological characterization of granule cells in the dentate gyrus immediately after birth

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    Andrea ePedroni

    2014-02-01

    Full Text Available Granule cells (GCs in the dentate gyrus are generated mainly postnatally. Between embryonic day 10 and 14, neural precursors migrate from the primary dentate matrix to the dentate gyrus where they differentiate into neurons. Neurogenesis reaches a peak at the end of the first postnatal week and it is completed at the end of the first postnatal month. This process continues at a reduced rate throughout life. Interestingly, immediately after birth, GCs exhibit a clear GABAergic phenotype. Only later they integrate the classical glutamatergic trisynaptic hippocampal circuit. Here, whole patch clamp recordings, in current clamp mode, were performed from immature GCs, intracellularly loaded with biocytin (in hippocampal slices from P0-P3 old rats in order to compare their morphological characteristics with their electrophysiological properties. The vast majority of GCs were very immature with small somata, few dendritic branches terminating with small varicosities and growth cones. In spite of their immaturity their axons reached often the CA3 area. Immature GCs generated, upon membrane depolarization, either rudimentary sodium spikes or more clear overshooting action potentials that fired repetitively. They exhibited also low threshold calcium spikes. In addition, most spiking neurons showed spontaneous synchronized network activity, reminiscent of giant depolarizing potentials (GDPs generated in the hippocampus by the synergistic action of glutamate and GABA, both depolarizing and excitatory. This early synchronized activity, absent during adult neurogenesis, may play a crucial role in the refinement of local neuronal circuits within the developing dentate gyrus.

  12. Offspring psychopathology following preconception, prenatal, and postnatal maternal bereavement stress

    Science.gov (United States)

    Class, Quetzal A.; Abel, Kathryn M.; Khashan, Ali S.; Rickert, Martin E.; Dalman, Christina; Larsson, Henrik; Hultman, Christina M.; Långström, Niklas; Lichtenstein, Paul; D’Onofrio, Brian M.

    2013-01-01

    Background Preconception, prenatal, and postnatal maternal stress are associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt, and completed suicide. Methods Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992–2000 for childhood outcomes and 2,155,221 offspring born 1973–1997 for adult outcomes with follow-up through 2009. Maternal stress was defined as death of a first degree relative during 6 months before conception, across pregnancy, or the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HR) in unadjusted and adjusted analyses. Results Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third trimester prenatal stress increased risk of ASD (adjusted HR=1.58, 95% CI: 1.15–2.17) and ADHD (adjusted HR=1.31, 95% CI: 1.04–1.66). First postnatal year stress increased risk for offspring suicide attempt (adjusted HR=1.13, 95% CI: 1.02–1.25) and completed suicide (adjusted HR=1.51, 95% CI: 1.08–2.11). Bereavement stress during the second postnatal year increased risk of ASD (adjusted HR=1.30, 95% CI: 1.09–1.55). Conclusions Further research is needed on associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases risk of offspring suicide attempt, completed suicide, and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes. PMID:23591021

  13. Dentate gyrus neurogenesis ablation via cranial irradiation enhances morphine self-administration and locomotor sensitization.

    Science.gov (United States)

    Bulin, Sarah E; Mendoza, Matthew L; Richardson, Devon R; Song, Kwang H; Solberg, Timothy D; Yun, Sanghee; Eisch, Amelia J

    2018-03-01

    Adult dentate gyrus (DG) neurogenesis is important for hippocampal-dependent learning and memory, but the role of new neurons in addiction-relevant learning and memory is unclear. To test the hypothesis that neurogenesis is involved in the vulnerability to morphine addiction, we ablated adult DG neurogenesis and examined morphine self-administration (MSA) and locomotor sensitization. Male Sprague-Dawley rats underwent hippocampal-focused, image-guided X-ray irradiation (IRR) to eliminate new DG neurons or sham treatment (Sham). Six weeks later, rats underwent either MSA (Sham = 16, IRR = 15) or locomotor sensitization (Sham = 12, IRR = 12). Over 21 days of MSA, IRR rats self-administered ~70 percent more morphine than Sham rats. After 28 days of withdrawal, IRR rats pressed the active lever 40 percent more than Sham during extinction. This was not a general enhancement of learning or locomotion, as IRR and Sham groups had similar operant learning and inactive lever presses. For locomotor sensitization, both IRR and Sham rats sensitized, but IRR rats sensitized faster and to a greater extent. Furthermore, dose-response revealed that IRR rats were more sensitive at a lower dose. Importantly, these increases in locomotor activity were not apparent after acute morphine administration and were not a byproduct of irradiation or post-irradiation recovery time. Therefore, these data, along with other previously published data, indicate that reduced hippocampal neurogenesis confers vulnerability for multiple classes of drugs. Thus, therapeutics to specifically increase or stabilize hippocampal neurogenesis could aid in preventing initial addiction as well as future relapse. © 2017 Society for the Study of Addiction.

  14. Orphan nuclear receptor TLX regulates astrogenesis by modulating BMP signaling

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    Song eQin

    2014-04-01

    Full Text Available Neural stem cells (NSCs are self-renewing multipotent progenitors that generate both neurons and glia. The precise control of NSC behavior is fundamental to the architecture and function of the central nervous system. We previously demonstrated that the orphan nuclear receptor TLX is required for postnatal NSC activation and neurogenesis in the neurogenic niche. Here, we show that TLX modulates BMP-SMAD signaling to control the timing of postnatal astrogenesis. Genes involved in the BMP signaling pathway, such as Bmp4, Hes1, and Id3, are upregulated in postnatal brains lacking Tlx. Chromatin immunoprecipitation and electrophoretic mobility shift assays reveal that TLX can directly bind the enhancer region of Bmp4. In accordance with elevated BMP signaling, the downstream effectors SMAD1/5/8 are activated by phosphorylation in Tlx mutant mice. Consequently, Tlx mutant brains exhibit an early appearance and increased number of astrocytes with marker expression of glial fibrillary acidic protein (GFAP and S100B. Taken together, these results suggest that TLX tightly controls postnatal astrogenesis through the modulation of BMP-SMAD signaling pathway activity.

  15. Orphan nuclear receptor TLX regulates astrogenesis by modulating BMP signaling.

    Science.gov (United States)

    Qin, Song; Niu, Wenze; Iqbal, Nida; Smith, Derek K; Zhang, Chun-Li

    2014-01-01

    Neural stem cells (NSCs) are self-renewing multipotent progenitors that generate both neurons and glia. The precise control of NSC behavior is fundamental to the architecture and function of the central nervous system. We previously demonstrated that the orphan nuclear receptor TLX is required for postnatal NSC activation and neurogenesis in the neurogenic niche. Here, we show that TLX modulates bone morphogenetic protein (BMP)-SMAD signaling to control the timing of postnatal astrogenesis. Genes involved in the BMP signaling pathway, such as Bmp4, Hes1, and Id3, are upregulated in postnatal brains lacking Tlx. Chromatin immunoprecipitation and electrophoretic mobility shift assays reveal that TLX can directly bind the enhancer region of Bmp4. In accordance with elevated BMP signaling, the downstream effectors SMAD1/5/8 are activated by phosphorylation in Tlx mutant mice. Consequently, Tlx mutant brains exhibit an early appearance and increased number of astrocytes with marker expression of glial fibrillary acidic protein (GFAP) and S100B. Taken together, these results suggest that TLX tightly controls postnatal astrogenesis through the modulation of BMP-SMAD signaling pathway activity.

  16. PMC-12, a traditional herbal medicine, enhances learning memory and hippocampal neurogenesis in mice.

    Science.gov (United States)

    Park, Hee Ra; Kim, Ju Yeon; Lee, Yujeong; Chun, Hye Jeong; Choi, Young Whan; Shin, Hwa Kyoung; Choi, Byung Tae; Kim, Cheol Min; Lee, Jaewon

    2016-03-23

    The beneficial effects of traditional Korean medicine are recognized during the treatment of neurodegenerative conditions, such as, Alzheimer's disease and neurocognitive dysfunction, and recently, hippocampal neurogenesis has been reported to be associated with memory function. In this study, the authors investigated the beneficial effects of polygonum multiflorum Thunberg complex composition-12 (PMC-12), which is a mixture of four medicinal herbs, that is, Polygonum multiflorum, Polygala tenuifolia, Rehmannia glutinosa, and Acorus gramineus, on hippocampal neurogenesis, learning, and memory in mice. PMC-12 was orally administered to male C57BL/6 mice (5 weeks old) at 100 or 500 mg/kg daily for 2 weeks. PMC-12 administration significantly was found to increase the proliferation of neural progenitor cells and the survival of newly-generated cells in the dentate gyrus. In the Morris water maze test, the latency times of PMC-12 treated mice (100 or 500 mg/kg) were shorter than those of vehicle-control mice. In addition, PMC-12 increased the levels of BDNF, p-CREB, and synaptophysin, which are known to be associated with neural plasticity and hippocampal neurogenesis. These findings suggest PMC-12 enhances hippocampal neurogenesis and neurocognitive function and imply that PMC-12 ameliorates memory impairment and cognitive deficits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Proteomic analysis of astrocytic secretion that regulates neurogenesis using quantitative amine-specific isobaric tagging

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    Yan, Hu; Zhou, Wenhao [Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Wei, Liming; Zhong, Fan [Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Roda, Shanghai 200032 (China); Yang, Yi, E-mail: yyang@shmu.edu.cn [Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China)

    2010-01-08

    Astrocytes are essential components of neurogenic niches that affect neurogenesis through membrane association and/or the release of soluble factors. To identify factors released from astrocytes that could regulate neural stem cell differentiation and proliferation, we used mild oxygen-glucose deprivation (OGD) to inhibit the secretory capacity of astrocytes. Using the Transwell co-culture system, we found that OGD-treated astrocytes could not promote neural stem cell differentiation and proliferation. Next, isobaric tagging for the relative and absolute quantitation (iTRAQ) proteomics techniques was performed to identify the proteins in the supernatants of astrocytes (with or without OGD). Through a multi-step analysis and gene ontology classification, 130 extracellular proteins were identified, most of which were involved in neuronal development, the inflammatory response, extracellular matrix composition and supportive functions. Of these proteins, 44 had never been reported to be produced by astrocytes. Using ProteinPilot software analysis, we found that 60 extracellular proteins were significantly altered (27 upregulated and 33 downregulated) in the supernatant of OGD-treated astrocytes. Among these proteins, 7 have been reported to be able to regulate neurogenesis, while others may have the potential to regulate neurogenesis. This study profiles the major proteins released by astrocytes, which play important roles in the modulation of neurogenesis.

  18. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

    Directory of Open Access Journals (Sweden)

    Sanberg Paul R

    2008-02-01

    Full Text Available Abstract Background Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation. Results We determined that human umbilical cord blood mononuclear cells (UCBMC given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis. Conclusion The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain.

  19. Proteomic analysis of astrocytic secretion that regulates neurogenesis using quantitative amine-specific isobaric tagging

    International Nuclear Information System (INIS)

    Yan, Hu; Zhou, Wenhao; Wei, Liming; Zhong, Fan; Yang, Yi

    2010-01-01

    Astrocytes are essential components of neurogenic niches that affect neurogenesis through membrane association and/or the release of soluble factors. To identify factors released from astrocytes that could regulate neural stem cell differentiation and proliferation, we used mild oxygen-glucose deprivation (OGD) to inhibit the secretory capacity of astrocytes. Using the Transwell co-culture system, we found that OGD-treated astrocytes could not promote neural stem cell differentiation and proliferation. Next, isobaric tagging for the relative and absolute quantitation (iTRAQ) proteomics techniques was performed to identify the proteins in the supernatants of astrocytes (with or without OGD). Through a multi-step analysis and gene ontology classification, 130 extracellular proteins were identified, most of which were involved in neuronal development, the inflammatory response, extracellular matrix composition and supportive functions. Of these proteins, 44 had never been reported to be produced by astrocytes. Using ProteinPilot software analysis, we found that 60 extracellular proteins were significantly altered (27 upregulated and 33 downregulated) in the supernatant of OGD-treated astrocytes. Among these proteins, 7 have been reported to be able to regulate neurogenesis, while others may have the potential to regulate neurogenesis. This study profiles the major proteins released by astrocytes, which play important roles in the modulation of neurogenesis.

  20. Dannelse af nye nerveceller i den voksne hjerne

    DEFF Research Database (Denmark)

    Poulsen, Frantz Rom; Meyer, Morten; Rasmussen, Jens Zimmer

    2003-01-01

    neurogenesis in the adult human brain. In particular two brain regions show continuous division of neural stem and progenitor cells generating neurons and glial cells, namely the subgranular zone of the dentate gyrus and the subventricular zones of the lateral ventricles. From the latter region newly generated......Generation of new nerve cells (neurogenesis) is normally considered to be limited to the fetal and early postnatal period. Thus, damaged nerve cells are not expected to be replaced by generation of new cells. The brain is, however, more plastic than previously assumed. This also includes...... neuroblasts (immature nerve cells) migrate toward the olfactory bulb where they differentiate into neurons. In the dentate gyrus the newly generated neurons become functionally integrated in the granule cell layer, where they are believed to be of importance to learning and memory. It is at present not known...

  1. Abrogated inflammatory response promotes neurogenesis in a murine model of Japanese encephalitis.

    Directory of Open Access Journals (Sweden)

    Sulagna Das

    2011-03-01

    Full Text Available Japanese encephalitis virus (JEV induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline.Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used.This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors.

  2. Discovery of efficient stimulators for adult hippocampal neurogenesis based on scaffolds in dragon's blood.

    Science.gov (United States)

    Liang, Jian-Hua; Yang, Liang; Wu, Si; Liu, Si-Si; Cushman, Mark; Tian, Jing; Li, Nuo-Min; Yang, Qing-Hu; Zhang, He-Ao; Qiu, Yun-Jie; Xiang, Lin; Ma, Cong-Xuan; Li, Xue-Meng; Qing, Hong

    2017-08-18

    Reduction of hippocampal neurogenesis caused by aging and neurological disorders would impair neural circuits and result in memory loss. A new lead compound (N-trans-3',4'-methylenedioxystilben-4-yl acetamide 27) has been discovered to efficiently stimulate adult rats' neurogenesis. In-depth structure-activity relationship studies proved the necessity of a stilbene scaffold that is absent in highly cytotoxic analogs such as chalcones and heteroaryl rings and inactive analogs such as diphenyl acetylene and diphenyl ethane, and validated the importance of an NH in the carboxamide and a methylenedioxy substituent on the benzene ring. Immunohistochemical staining and biochemical analysis indicate, in contrast to previously reported neuroprotective chemicals, N-stilbenyl carboxamides have extra capacity for neuroproliferation-type neurogenesis, thereby providing a foundation for improving the plasticity of the adult mammalian brain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. LRRK2: an éminence grise of Wnt-mediated neurogenesis?

    Directory of Open Access Journals (Sweden)

    Daniel C Berwick

    2013-05-01

    Full Text Available The importance of Leucine-Rich Repeat Kinase 2 (LRRK2 to mature neurons is well-established, since mutations in PARK8, the gene encoding LRRK2, are the most common known cause of Parkinson’s disease. Nonetheless, despite the LRRK2 knockout mouse having no overt neurodevelopmental defect, numerous lines of in vitro data point towards a central role for this protein in neurogenesis. Roles for LRRK2 have been described in many key processes, including neurite outgrowth and the regulation of microtubule dynamics. Moreover, LRRK2 has been implicated in cell cycle control, suggesting additional roles in neurogenesis that precede terminal differentiation. However, we contend that the suggested function of LRRK2 as a scaffolding protein at the heart of numerous Wnt signaling cascades provides the most tantalizing link to neurogenesis in the developing brain. Numerous lines of evidence show a critical requirement for multiple Wnt pathways in the development of certain brain regions, not least the dopaminergic neurons of the ventral mid-brain. In conclusion, these observations indicate a function of LRRK2 as a subtle yet critical mediator of the action of Wnt ligands on developing neurons. We suggest that LRRK2 loss- or gain-of-function are likely modifiers of developmental phenotypes seen in animal models of Wnt signaling deregulation, a hypothesis that can be tested by cross-breeding relevant genetically modified experimental strains.

  4. Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

    Science.gov (United States)

    Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

    2016-02-01

    Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. On the Role of Neurogenesis and Neural Plasticity in the Evolution of Animal Personalities and Stress Coping Styles

    DEFF Research Database (Denmark)

    Overli, Oyvind; Sorensen, Christina

    2016-01-01

    and neurogenesis have received recent attention. This work reveals that brain cell proliferation and neurogenesis are associated with heritable variation in stress coping style, and they are also differentially affected by short- and long-term stress in a biphasic manner. Routine-dependent and inflexible behavior...... are conserved throughout the vertebrate subphylum, including factors affecting perception, learning, and memory of stimuli and events. Here we review conserved aspects of the contribution of neurogenesis and other aspects of neural plasticity to stress coping. In teleost fish, brain cell proliferation...

  6. Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations.

    Science.gov (United States)

    Lee, Alison; Mathilda Chiu, Yueh-Hsiu; Rosa, Maria José; Jara, Calvin; Wright, Robert O; Coull, Brent A; Wright, Rosalind J

    2016-09-01

    Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. We examined associations between prenatal and/or postnatal stress and children's asthma (n = 765) and effect modification by sex in a prospective cohort study. Maternal negative life events were ascertained prenatally and postpartum. Negative life event scores were categorized as 0, 1 to 2, 3 to 4, or 5 or greater to assess exposure-response relationships. We examined effects of prenatal and postnatal stress on children's asthma by age 6 years, modeling each as independent predictors, mutually adjusting for prenatal and postnatal stress, and finally considering interactions between prenatal and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. When considering stress in each period independently, among boys, a dose-response relationship was evident for each level increase on the ordinal scale prenatally (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P value for trend = .03) and postnatally (OR, 1.53; 95% CI, 1.16-2.01; P value for trend = .001); among girls, only the postnatal trend was significant (OR, 1.60; 95% CI, 1.14-2.22; P value for trend = .005). Higher stress in both the prenatal and postnatal periods was associated with increased odds of receiving a diagnosis of asthma in girls (OR, 1.37; 95% CI, 0.98-1.91; Pinteraction = .07) but not boys (OR, 1.08; 95% CI, 0.82-1.42; Pinteraction = .61). Although boys were more vulnerable to stress during the prenatal period, girls were more affected by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early-life stress might provide unique insight into the cause and natural history of asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Delayed behavioral dysfunctions following exposure to ionising radiation: role of neurogenesis

    International Nuclear Information System (INIS)

    Haridas, Seenu; Kumar, Mayank; Manda, Kailash

    2014-01-01

    Being a terminally differentiated organ, the brain has been considered to be a radioresistant one. Traditionally, delayed radiation-induced CNS damage was hypothesized as chiefly attributable to impaired vascular endothelial system and neuroinflammatory glial cell populations. In the recent decades, preclinical studies have focused on the hippocampal dentate gyrus, one of two discrete sites of the brain where adult neurogenesis takes place. Neurogenesis, in such area of the brain takes place throughout the adulthood and makes the brain highly vulnerable to the radiation. Recent investigations, including our own reports indicated that radiation ablates hippocampal neurogenesis, alters neuronal function, and induces neuroinflammation. Since the hippocampus is involved in learning and memory, behavioral adaptation and HPA axis regulation, damage by radiation leads to severe behavioral and cognitive dysfunctions. The present study aimed at evaluating the delayed effects of gamma-irradiation on the cognitive and affective functions, which were further corroborated to changes in neurogenesis. C57BL/6J mice were exposed to whole body irradiation as well as cranial irradiation by gamma-rays at different sub-lethal doses. The behavioral tests, consisting spontaneous motor activity, open field test, novel object recognition test, forced swim test and Morris water maze were performed at 1 month and 5 months post-exposure. Neurogenic potential was evaluated using flow-cytometry (FC) and immuno-histo-chemistry (IHC). The results indicated the significant changes in the affective and cognitive functions at delayed time points of radiation exposure. Profound alteration in the anxiety and depressive phenotype was observed following irradiation. Additionally, both long term and short term memory functions were disrupted, which were attributable to changes in the neurogenic potential as reported in the terms of BrdU positive cells using FC and IHC. Present investigation clearly

  8. S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal valproic acid exposure in very young mice.

    Science.gov (United States)

    Ornoy, Asher; Weinstein-Fudim, Liza; Tfilin, Matanel; Ergaz, Zivanit; Yanai, Joseph; Szyf, Moshe; Turgeman, Gadi

    2018-01-16

    A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight. From day 50, we carried out neurobehavioral tests and assessment of the antioxidant status of the prefrontal cerebral cortex, liver assessing SOD and CAT activity, lipid peroxidation and the expression of antioxidant genes. Mice injected with VPA exhibited neurobehavioral deficits typical of ASD that were more prominent in males. Changes in the activity of SOD and CAT increased lipid peroxidation and changes in the expression of antioxidant genes were observed in the prefrontal cortex of VPA treated mice, more prominent in females, while ASD like behavior was more prominent in males. There were no changes in the redox potential of the liver. The co-administration of VPA and SAM alleviated most ASD like neurobehavioral symptoms and normalized the redox potential in the prefrontal cortex. Early postnatal VPA administration induces ASD like behavior that is more severe in males, while the redox status changes are more severe in females; SAM corrects both. VPA-induced ASD seems to result from epigenetic changes, while the redox status changes may be secondary. Copyright © 2018. Published by Elsevier Inc.

  9. Maternal deprivation decelerates postnatal morphological lung development of F344 rats.

    Science.gov (United States)

    Hupa, Katharina Luise; Schmiedl, Andreas; Pabst, Reinhard; Von Hörsten, Stephan; Stephan, Michael

    2014-02-01

    Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide-cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4-dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4-deficient rats, due to a significant deceleration already induced by DPP4-deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4-system. Copyright © 2013 Wiley Periodicals, Inc.

  10. Using High Performance Computing to Examine the Processes of Neurogenesis Underlying Pattern Separation and Completion of Episodic Information.

    Energy Technology Data Exchange (ETDEWEB)

    Aimone, James Bradley; Bernard, Michael Lewis; Vineyard, Craig Michael; Verzi, Stephen Joseph.

    2014-10-01

    Adult neurogenesis in the hippocampus region of the brain is a neurobiological process that is believed to contribute to the brain's advanced abilities in complex pattern recognition and cognition. Here, we describe how realistic scale simulations of the neurogenesis process can offer both a unique perspective on the biological relevance of this process and confer computational insights that are suggestive of novel machine learning techniques. First, supercomputer based scaling studies of the neurogenesis process demonstrate how a small fraction of adult-born neurons have a uniquely larger impact in biologically realistic scaled networks. Second, we describe a novel technical approach by which the information content of ensembles of neurons can be estimated. Finally, we illustrate several examples of broader algorithmic impact of neurogenesis, including both extending existing machine learning approaches and novel approaches for intelligent sensing.

  11. Adult neurogenesis modifies excitability of the dentate gyrus

    Directory of Open Access Journals (Sweden)

    Taruna eIkrar

    2013-12-01

    Full Text Available Adult-born dentate granule neurons contribute to memory encoding functions of the dentate gyrus (DG such as pattern separation. However, local circuit-mechanisms by which adult-born neurons partake in this process are poorly understood. Computational, neuroanatomical and electrophysiological studies suggest that sparseness of activation in the granule cell layer (GCL is conducive for pattern separation. A sparse coding scheme is thought to facilitate the distribution of similar entorhinal inputs across the GCL to decorrelate overlapping representations and minimize interference. Here we used fast voltage-sensitive dye (VSD imaging combined with laser photostimulation and electrical stimulation to examine how selectively increasing adult DG neurogenesis influences local circuit activity and excitability. We show that DG of mice with more adult-born neurons exhibits decreased strength of neuronal activation and more restricted excitation spread in GCL while maintaining effective output to CA3c. Conversely, blockade of adult hippocampal neurogenesis changed excitability of the DG in the opposite direction. Analysis of GABAergic inhibition onto mature dentate granule neurons in the DG of mice with more adult-born neurons shows a modest readjustment of perisomatic inhibitory synaptic gain without changes in overall inhibitory tone, presynaptic properties or GABAergic innervation pattern. Retroviral labeling of connectivity in mice with more adult-born neurons showed increased number of excitatory synaptic contacts of adult-born neurons onto hilar interneurons. Together, these studies demonstrate that adult hippocampal neurogenesis modifies excitability of mature dentate granule neurons and that this non-cell autonomous effect may be mediated by local circuit mechanisms such as excitatory drive onto hilar interneurons. Modulation of DG excitability by adult-born dentate granule neurons may enhance sparse coding in the GCL to influence pattern

  12. Chinese herbal medicine for Alzheimer's disease: Clinical evidence and possible mechanism of neurogenesis.

    Science.gov (United States)

    Yang, Wen-Ting; Zheng, Xia-Wei; Chen, Shuang; Shan, Chun-Shuo; Xu, Qing-Qing; Zhu, Jia-Zhen; Bao, Xiao-Yi; Lin, Yan; Zheng, Guo-Qing; Wang, Yan

    2017-10-01

    Currently, there is lack of cure or disease-modifying treatment for Alzheimer's disease (AD). Chinese herbal medicine (CHM) is purported to ameliorate AD progression, perhaps by promoting hippocampal neurogenesis. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for AD based on high-quality randomized controlled trials (RCTs) and reviewed its possible mechanisms of neurogenesis according to animal-based researches. Twenty eligible studies with 1767 subjects were identified in eight database searches from inception to February 2017. The studies investigated the CHM versus placebo (n=3), CHM versus donepezil (n=9 with 10 comparisons), CHM plus donepezil versus donepezil (n=3), CHM versus a basic treatment (n=3), and CHM plus basic treatment versus basic treatment (n=2). Adverse events were reported in 11 studies, analyzed but not observed in 3 studies, and not analyzed in 6 studies. The main findings of present study are that CHM as adjuvant therapy exerted an additive anti-AD benefit, whereas the efficacy of CHM as a monotherapy was inconclusive. Additionally, CHMs were generally safe and well tolerated in AD patients. Active molecules in frequent constituents of CHMs can alter multiple critical signaling pathways regulating neurogenesis. Thus, the present evidence supports, to a limited extent, the conclusion that CHM can be recommended for routine use in AD patients and its possible mechanism enhances adult hippocampal neurogenesis through activating the multi-signal pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Selective noradrenaline depletion impairs working memory and hippocampal neurogenesis.

    Science.gov (United States)

    Coradazzi, Marino; Gulino, Rosario; Fieramosca, Francesco; Falzacappa, Lucia Verga; Riggi, Margherita; Leanza, Giampiero

    2016-12-01

    Noradrenergic neurons in the locus coeruleus play a role in learning and memory, and their loss is an early event in Alzheimer's disease pathogenesis. Moreover, noradrenaline may sustain hippocampal neurogenesis; however, whether are these events related is still unknown. Four to five weeks following the selective immunotoxic ablation of locus coeruleus neurons, young adult rats underwent reference and working memory tests, followed by postmortem quantitative morphological analyses to assess the extent of the lesion, as well as the effects on proliferation and/or survival of neural progenitors in the hippocampus. When tested in the Water Maze task, lesioned animals exhibited no reference memory deficit, whereas working memory abilities were seen significantly impaired, as compared with intact or sham-lesioned controls. Stereological analyses confirmed a dramatic noradrenergic neuron loss associated to reduced proliferation, but not survival or differentiation, of 5-bromo-2'deoxyuridine-positive progenitors in the dentate gyrus. Thus, ascending noradrenergic afferents may be involved in more complex aspects of cognitive performance (i.e., working memory) possibly via newly generated progenitors in the hippocampus. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Sex-specific effects of prenatal and postnatal nutritional conditions on the oxidative status of great tit nestlings.

    Science.gov (United States)

    Giordano, M; Costantini, D; Tschirren, B

    2015-01-01

    The early life period is characterized by fast growth and development, which can lead to high reactive oxygen species (ROS) production. Young animals thus have to balance their investment in growth versus ROS defence, and this balance is likely mediated by resource availability. Consequently resources transferred prenatally by the mother and nutritional conditions experienced shortly after birth may crucially determine the oxidative status of young animals. Here, we experimentally investigated the relative importance of pre- and early postnatal nutritional conditions on the oxidative status of great tit nestlings (Parus major). We show that resources transferred by the mother through the egg and nutritional conditions encountered after hatching affect the oxidative status of nestling in a sex-specific way. Daughters of non-supplemented mothers and daughters which did not receive extra food during the early postnatal period had higher oxidative damage than sons, while no differences between sons and daughters were found when extra food was provided pre- or postnatally. No effect of the food supplementations on growth, fledging mass or tarsus length was observed, indicating that female nestlings maintained their investment in growth at the expense of ROS defence mechanisms when resources were limited. The lower priority of the antioxidant defence system for female nestlings was also evidenced by lower levels of specific antioxidant components. These results highlight the important role of early parental effects in shaping oxidative stress in the offspring, and show that the sensitivity to these parental effects is sex-specific.

  15. Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy.

    Science.gov (United States)

    Stahl, Andreas; Chen, Jing; Sapieha, Przemyslaw; Seaward, Molly R; Krah, Nathan M; Dennison, Roberta J; Favazza, Tara; Bucher, Felicitas; Löfqvist, Chatarina; Ong, Huy; Hellström, Ann; Chemtob, Sylvain; Akula, James D; Smith, Lois E H

    2010-12-01

    In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r(2) = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome.

  16. Dietary zinc supplementation throughout pregnancy protects against fetal dysmorphology and improves postnatal survival after prenatal ethanol exposure in mice.

    Science.gov (United States)

    Summers, Brooke L; Rofe, Allan M; Coyle, Peter

    2009-04-01

    We have previously demonstrated that ethanol teratogenicity is associated with metallothionein-induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol-related dysmorphology. Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60. Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn-supplemented fetuses was not different from saline-treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre- or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un-supplemented groups. These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy.

  17. Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models.

    Directory of Open Access Journals (Sweden)

    Juan Jose Ramos-Rodriguez

    Full Text Available Type 2 diabetes (T2D is an important risk factor to suffer dementia, including Alzheimer's disease (AD, and some neuropathological features observed in dementia could be mediated by T2D metabolic alterations. Since brain atrophy and impaired neurogenesis have been observed both T2D and AD we analyzed central nervous system (CNS morphological alterations in the db/db mice (leptin receptor KO mice, as a model of long-term insulin resistance and T2D, and in C57Bl6 mice fed with high fat diet (HFD, as a model of diet induced insulin resistance and prediabetes. Db/db mice showed an age-dependent cortical and hippocampal atrophy, whereas in HFD mice cortex and hippocampus were preserved. We also detected increased neurogenesis and cell proliferation rates in young db/db mice when compared with control littermates. Our study shows that metabolic parameters serve as predictors of both atrophy and altered proliferation and neurogenesis in the CNS. Moreover in the cortex, atrophy, cell proliferation and neurogenesis were significantly correlated. Our data suggest that T2D may underline some of the pathological features observed in the dementia process. They also support that blood glucose control in elderly patients could help to slow down dementia evolution and maybe, improve its prognosis.

  18. Prenatal and Postnatal Cell Phone Exposures and Headaches in Children.

    Science.gov (United States)

    Sudan, Madhuri; Kheifets, Leeka; Arah, Onyebuchi; Olsen, Jorn; Zeltzer, Lonnie

    2012-12-05

    Children today are exposed to cell phones early in life, and may be at the greatest risk if exposure is harmful to health. We investigated associations between cell phone exposures and headaches in children. The Danish National Birth Cohort enrolled pregnant women between 1996 and 2002. When their children reached age seven years, mothers completed a questionnaire regarding the child's health, behaviors, and exposures. We used multivariable adjusted models to relate prenatal only, postnatal only, or both prenatal and postnatal cell phone exposure to whether the child had migraines and headache-related symptoms. Our analyses included data from 52,680 children. Children with cell phone exposure had higher odds of migraines and headache-related symptoms than children with no exposure. The odds ratio for migraines was 1.30 (95% confidence interval: 1.01-1.68) and for headache-related symptoms was 1.32 (95% confidence interval: 1.23-1.40) for children with both prenatal and postnatal exposure. In this study, cell phone exposures were associated with headaches in children, but the associations may not be causal given the potential for uncontrolled confounding and misclassification in observational studies such as this. However, given the widespread use of cell phones, if a causal effect exists it would have great public health impact.

  19. Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate

    Directory of Open Access Journals (Sweden)

    Timothy J. Petros

    2015-11-01

    Full Text Available Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.

  20. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

    Directory of Open Access Journals (Sweden)

    Bruno P. Carreira

    2015-01-01

    Full Text Available Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO. In these conditions, NO promotes proliferation of neural stem cells (NSC in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.

  1. Innovative look at dairy heifer rearing: Effect of prenatal and post-natal environment on later performance.

    Science.gov (United States)

    Van Eetvelde, M; Opsomer, G

    2017-08-01

    As heifer rearing is a costly investment, dairy farmers have been stimulated to maximize early growth of their calves, mainly by enhanced liquid feeding. However, the long-term effects of this "accelerated growth" are largely unknown. Studies recently performed at Ghent University indicate that in dairy cattle, certain maternal factors (such as young age and high milk yield) and environmental factors (such as high ambient temperatures) create a suboptimal environment for the developing foetus, altering the phenotype of the newborn calf. According to the "thrifty phenotype hypothesis," these metabolic alterations prepare the newborn for similar ("matching") conditions after birth, enhancing its survival during periods of limited feeding. Yet, when an abundance of nutrients is available in post-natal life (e.g., during periods of enhanced feeding), the "mismatch" between pre- and post-natal environment results in an early catch-up growth, with potential negative consequences. The aim of the article was to discuss this mismatch between pre- and post-natal environment in dairy calves. Previous studies, especially in human medicine, have shown catch-up growth to be associated with obesity, fertility problems, metabolic diseases and a reduced lifespan. Hence, we hypothesize that, by applying programs of accelerated growth, our current management system accentuates the mismatch between the pre- and post-natal environment in dairy calves. We can conclude that, although more research is necessary, the current findings point towards a more individual approach when rearing dairy heifers. © 2017 Blackwell Verlag GmbH.

  2. Matching Diabetes and Alcoholism: Oxidative Stress, Inflammation, and Neurogenesis Are Commonly Involved

    Directory of Open Access Journals (Sweden)

    Jorge M. Barcia

    2015-01-01

    Full Text Available Diabetes and alcohol misuse are two of the major challenges in health systems worldwide. These two diseases finally affect several organs and systems including the central nervous system. Hippocampus is one of the most relevant structures due to neurogenesis and memory-related processing among other functions. The present review focuses on the common profile of diabetes and ethanol exposure in terms of oxidative stress and proinflammatory and prosurvival recruiting transcription factors affecting hippocampal neurogenesis. Some aspects around antioxidant strategies are also included. As a global conclusion, the present review points out some common hits on both diseases giving support to the relations between alcohol intake and diabetes.

  3. Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yuqin Ye

    2017-01-01

    Full Text Available The protective role of electroacupuncture (EA treatment in diverse neurological diseases such as ischemic stroke is well acknowledged. However, whether and how EA act on hippocampal neurogenesis following traumatic brain injury (TBI remains poorly understood. This study aims to investigate the effect of EA on hippocampal neurogenesis and neurological functions, as well as its underlying association with toll-like receptor 4 (TLR4 signaling in TBI mice. BrdU/NeuN immunofluorescence was performed to label newborn neurons in the hippocampus after EA treatment. Water maze test and neurological severity score were used to evaluate neurological function posttrauma. The hippocampal level of TLR4 and downstream molecules and inflammatory cytokines were, respectively, detected by Western blot and enzyme-linked immunosorbent assay. EA enhanced hippocampal neurogenesis and inhibited TLR4 expression at 21, 28, and 35 days after TBI, but the beneficial effects of EA on posttraumatic neurogenesis and neurological functions were attenuated by lipopolysaccharide-induced TLR4 activation. In addition, EA exerted an inhibitory effect on both TLR4/Myd88/NF-κB and TLR4/TRIF/NF-κB pathways, as well as the inflammatory cytokine expression in the hippocampus following TBI. In conclusion, EA promoted hippocampal neurogenesis and neurological recovery through inhibition of TLR4 signaling pathway posttrauma, which may be a potential approach to improve the outcome of TBI.

  4. Early Postnatal Diets Affect the Bioregional Small Intestine Microbiome and Ileal Metabolome in Neonatal Pigs.

    Science.gov (United States)

    Piccolo, Brian D; Mercer, Kelly E; Bhattacharyya, Sudeepa; Bowlin, Anne K; Saraf, Manish K; Pack, Lindsay; Chintapalli, Sree V; Shankar, Kartik; Adams, Sean H; Badger, Thomas M; Yeruva, Laxmi

    2017-08-01

    Background: Breastfeeding is known to be protective against gastrointestinal disorders and may modify gut development. Although the gut microbiome has been implicated, little is known about how early diet affects the small intestine microbiome. Objective: We hypothesized that disparate early diets would promote unique microbial profiles in the small intestines of neonatal pigs. Methods: Male and female 2-d-old White Dutch Landrace pigs were either sow fed or provided dairy (Similac Advance powder; Ross Products Abbott Laboratories) or soy (Enfamil Prosobee Lipil powder; Mead Johnson Nutritionals) infant formulas until day 21. Bacterial ecology was assessed in the contents of the small intestine through the use of 16S ribosomal RNA sequencing. α-Diversity, β-diversity, and differential abundances of operational taxonomic units were assessed by ANOVA, permutational ANOVA, and negative binomial regression, respectively. Ileum tissue metabolomics were measured by LC-mass spectrometry and assessed by weighted correlation network analysis. Results: Greater α-diversity was observed in the duodena of sow-fed compared with formula-fed neonatal pigs ( P 60% relative abundance in all of the groups. In the duodenum, 77 genera were altered by diet, followed by 48 in the jejunum and 19 in the ileum. Metabolomics analyses revealed associations between ileum tissue metabolites (e.g., acylcarnitines, 3-aminoisobutyric acid) and diet-responsive microbial genera. Conclusions: These results indicate that the neonatal diet has regional effects on the small intestine microbiome in pigs, with the most pronounced effects occurring in the duodena. Regional effects may be important factors when considering gut tissue metabolism and development in the postnatal period. © 2017 American Society for Nutrition.

  5. Influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats.

    Science.gov (United States)

    Kim, Hong; Lee, Myoung-Hwa; Chang, Hyun-Kyung; Lee, Taeck-Hyun; Lee, Hee-Hyuk; Shin, Min-Chul; Shin, Mal-Soon; Won, Ran; Shin, Hye-Sook; Kim, Chang-Ju

    2006-03-01

    During the prenatal period, the development of individual is influenced by the environmental factors. In the present study, the influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats was investigated. The exposure to the noise during pregnancy caused growth retardation, decreased neurogenesis in the hippocampus, and impaired spatial learning ability in pups. The exposure to music during pregnancy, on the other hand, caused increased neurogenesis in the hippocampus and enhanced spatial learning ability in pups. The present study has shown the importance of the prenatal environmental conditions for the cognition and brain development.

  6. 56Fe particle exposure results in a long-lasting increase in a cellular index of genomic instability and transiently suppresses adult hippocampal neurogenesis in vivo

    Science.gov (United States)

    DeCarolis, Nathan A.; Rivera, Phillip D.; Ahn, Francisca; Amaral, Wellington Z.; LeBlanc, Junie A.; Malhotra, Shveta; Shih, Hung-Ying; Petrik, David; Melvin, Neal R.; Chen, Benjamin P. C.; Eisch, Amelia J.

    2014-07-01

    The high-LET HZE particles from galactic cosmic radiation pose tremendous health risks to astronauts, as they may incur sub-threshold brain injury or maladaptations that may lead to cognitive impairment. The health effects of HZE particles are difficult to predict and unfeasible to prevent. This underscores the importance of estimating radiation risks to the central nervous system as a whole as well as to specific brain regions like the hippocampus, which is central to learning and memory. Given that neurogenesis in the hippocampus has been linked to learning and memory, we investigated the response and recovery of neurogenesis and neural stem cells in the adult mouse hippocampal dentate gyrus after HZE particle exposure using two nestin transgenic reporter mouse lines to label and track radial glia stem cells (Nestin-GFP and Nestin-CreERT2/R26R:YFP mice, respectively). Mice were subjected to 56Fe particle exposure (0 or 1 Gy, at either 300 or 1000 MeV/n) and brains were harvested at early (24 h), intermediate (7 d), and/or long time points (2-3 mo) post-irradiation. 56Fe particle exposure resulted in a robust increase in 53BP1+ foci at both the intermediate and long time points post-irradiation, suggesting long-term genomic instability in the brain. However, 56Fe particle exposure only produced a transient decrease in immature neuron number at the intermediate time point, with no significant decrease at the long time point post-irradiation. 56Fe particle exposure similarly produced a transient decrease in dividing progenitors, with fewer progenitors labeled at the early time point but equal number labeled at the intermediate time point, suggesting a recovery of neurogenesis. Notably, 56Fe particle exposure did not change the total number of nestin-expressing neural stem cells. These results highlight that despite the persistence of an index of genomic instability, 56Fe particle-induced deficits in adult hippocampal neurogenesis may be transient. These data support

  7. Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain

    Directory of Open Access Journals (Sweden)

    Michalina Respondek

    2015-12-01

    Full Text Available Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC, which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

  8. Using High Performance Computing to Examine the Processes of Neurogenesis Underlying Pattern Separation/Completion of Episodic Information.

    Energy Technology Data Exchange (ETDEWEB)

    Aimone, James Bradley [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Betty, Rita [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-01

    Using High Performance Computing to Examine the Processes of Neurogenesis Underlying Pattern Separation/Completion of Episodic Information - Sandia researchers developed novel methods and metrics for studying the computational function of neurogenesis, thus generating substantial impact to the neuroscience and neural computing communities. This work could benefit applications in machine learning and other analysis activities.

  9. Postnatal depression and socio-cultural practices among postnatal mothers in Kota Bahru, Kelantan, Malaysia.

    Science.gov (United States)

    Azidah, A K; Shaiful, B I; Rusli, N; Jamil, M Y

    2006-03-01

    This is a cross sectional study to determine the relationship of postnatal depression (PND) and socio-cultural practices post-delivery among women in Kota Bharu, Kelantan. Four hundred and twenty one pregnant women were screened for depression between 36 - 42 weeks of pregnancy, 1 week and 4 - 6 weeks postpartum using Edinburgh Postnatal Depression Scale (EPDS). The women also completed questionnaires on socio-demography, psychosocial support and traditional postnatal care. The prevalence of PND at 4-6 weeks postpartum was 20.7%. Depressive symptoms at the end of pregnancy (p<0.05) and one week postpartum (p<0.05), worry about the baby (p<0.05), use of traditional medication (p<0.05) and traditional massage (p<0.05) were significantly associated with PND.

  10. The experiences of postnatal patients regarding postnatal care in ...

    African Journals Online (AJOL)

    At home they receive care and advice from traditional birth attendants. ... exploratory, descriptive and contextual research method was used in this study. ... relatives when giving health advice on discharge; conflicting postnatal care advice; ...

  11. Recent Advances on the Role of Neurogenesis in the Adult Brain: Therapeutic Potential in Parkinson's and Alzheimer's Diseases.

    Science.gov (United States)

    Radad, Khaled; Moldzio, Rudolf; Al-Shraim, Mubarak; Kranner, Barbara; Krewenka, Christopher; Rausch, Wolf-Dieter

    2017-01-01

    Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus. These discoveries question a long standing dogma on nervous system regeneration and provide medical science with potential new strategies to harness the process of neurogenesis for treating neurological disabilities and neurodegenerative diseases. In this current review, we address the most recent advances on the role of neurogenesis in the adult brain and therapeutic potential in the two most common neurodegenerative disorders, Parkinson's and Alzheimer's diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Untangling the influences of voluntary running, environmental complexity, social housing and stress on adult hippocampal neurogenesis.

    Directory of Open Access Journals (Sweden)

    Catherine-Alexandra Grégoire

    Full Text Available Environmental enrichment (EE exerts powerful effects on brain physiology, and is widely used as an experimental and therapeutic tool. Typical EE paradigms are multifactorial, incorporating elements of physical exercise, environmental complexity, social interactions and stress, however the specific contributions of these variables have not been separable using conventional housing paradigms. Here, we evaluated the impacts of these individual variables on adult hippocampal neurogenesis by using a novel "Alternating EE" paradigm. For 4 weeks, adult male CD1 mice were alternated daily between two enriched environments; by comparing groups that differed in one of their two environments, the individual and combinatorial effects of EE variables could be resolved. The Alternating EE paradigm revealed that (1 voluntary running for 3 days/week was sufficient to increase both mitotic and post-mitotic stages of hippocampal neurogenesis, confirming the central importance of exercise; (2 a complex environment (comprised of both social interactions and rotated inanimate objects had no effect on neurogenesis itself, but enhanced depolarization-induced c-Fos expression (attributable to social interactions and buffered stress-induced plasma corticosterone levels (attributable to inanimate objects; and (3 neither social isolation, group housing, nor chronically increased levels of plasma corticosterone had a prolonged impact on neurogenesis. Mouse strain, handling and type of running apparatus were tested and excluded as potential confounding factors. These findings provide valuable insights into the relative effects of key EE variables on adult neurogenesis, and this "Alternating EE" paradigm represents a useful tool for exploring the contributions of individual EE variables to mechanisms of neural plasticity.

  13. Toll-like receptor 2 promotes neurogenesis from the dentate gyrus after photothrombotic cerebral ischemia in mice.

    Science.gov (United States)

    Seong, Kyung-Joo; Kim, Hyeong-Jun; Cai, Bangrong; Kook, Min-Suk; Jung, Ji-Yeon; Kim, Won-Jae

    2018-03-01

    The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

  14. Untangling the Influences of Voluntary Running, Environmental Complexity, Social Housing and Stress on Adult Hippocampal Neurogenesis

    Science.gov (United States)

    Grégoire, Catherine-Alexandra; Bonenfant, David; Le Nguyen, Adalie; Aumont, Anne; Fernandes, Karl J. L.

    2014-01-01

    Environmental enrichment (EE) exerts powerful effects on brain physiology, and is widely used as an experimental and therapeutic tool. Typical EE paradigms are multifactorial, incorporating elements of physical exercise, environmental complexity, social interactions and stress, however the specific contributions of these variables have not been separable using conventional housing paradigms. Here, we evaluated the impacts of these individual variables on adult hippocampal neurogenesis by using a novel “Alternating EE” paradigm. For 4 weeks, adult male CD1 mice were alternated daily between two enriched environments; by comparing groups that differed in one of their two environments, the individual and combinatorial effects of EE variables could be resolved. The Alternating EE paradigm revealed that (1) voluntary running for 3 days/week was sufficient to increase both mitotic and post-mitotic stages of hippocampal neurogenesis, confirming the central importance of exercise; (2) a complex environment (comprised of both social interactions and rotated inanimate objects) had no effect on neurogenesis itself, but enhanced depolarization-induced c-Fos expression (attributable to social interactions) and buffered stress-induced plasma corticosterone levels (attributable to inanimate objects); and (3) neither social isolation, group housing, nor chronically increased levels of plasma corticosterone had a prolonged impact on neurogenesis. Mouse strain, handling and type of running apparatus were tested and excluded as potential confounding factors. These findings provide valuable insights into the relative effects of key EE variables on adult neurogenesis, and this “Alternating EE” paradigm represents a useful tool for exploring the contributions of individual EE variables to mechanisms of neural plasticity. PMID:24465980

  15. Age-dependent role for Ras-GRF1 in the late stages of adult neurogenesis in the dentate gyrus.

    Science.gov (United States)

    Darcy, Michael J; Trouche, Stéphanie; Jin, Shan-Xue; Feig, Larry A

    2014-03-01

    The dentate gyrus of the hippocampus plays a pivotal role in pattern separation, a process required for the behavioral task of contextual discrimination. One unique feature of the dentate gyrus that contributes to pattern separation is adult neurogenesis, where newly born neurons play a distinct role in neuronal circuitry. Moreover,the function of neurogenesis in this brain region differs in adolescent and adult mice. The signaling mechanisms that differentially regulate the distinct steps of adult neurogenesis in adolescence and adulthood remain poorly understood. We used mice lacking RASGRF1(GRF1), a calcium-dependent exchange factor that regulates synaptic plasticity and participates in contextual discrimination performed by mice, to test whether GRF1 plays a role in adult neurogenesis.We show Grf1 knockout mice begin to display a defect in neurogenesis at the onset of adulthood (~2 months of age), when wild-type mice first acquire the ability to distinguish between closely related contexts. At this age, young hippocampal neurons in Grf1 knockout mice display severely reduced dendritic arborization. By 3 months of age, new neuron survival is also impaired. BrdU labeling of new neurons in 2-month-old Grf1 knockout mice shows they begin to display reduced survival between 2 and 3 weeks after birth, just as new neurons begin to develop complex dendritic morphology and transition into using glutamatergic excitatory input. Interestingly, GRF1 expression appears in new neurons at the developmental stage when GRF1 loss begins to effect neuronal function. In addition, we induced a similar loss of new hippocampal neurons by knocking down expression of GRF1 solely in new neurons by injecting retrovirus that express shRNA against GRF1 into the dentate gyrus. Together, these findings show that GRF1 expressed in new neurons promotes late stages of adult neurogenesis. Overall our findings show GRF1 to be an age-dependent regulator of adult hippocampal neurogenesis, which

  16. HIPPOCAMPAL ADULT NEUROGENESIS: ITS REGULATION AND POTENTIAL ROLE IN SPATIAL LEARNING AND MEMORY

    Science.gov (United States)

    Lieberwirth, Claudia; Pan, Yongliang; Liu, Yan; Zhang, Zhibin; Wang, Zuoxin

    2016-01-01

    Adult neurogenesis, defined here as progenitor cell division generating functionally integrated neurons in the adult brain, occurs within the hippocampus of numerous mammalian species including humans. The present review details various endogenous (e.g., neurotransmitters) and environmental (e.g., physical exercise) factors that have been shown to influence hippocampal adult neurogenesis. In addition, the potential involvement of adult-generated neurons in naturally-occurring spatial learning behavior is discussed by summarizing the literature focusing on traditional animal models (e.g., rats and mice), non-traditional animal models (e.g., tree shrews), as well as natural populations (e.g., chickadees and Siberian chipmunk). PMID:27174001

  17. Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network

    Directory of Open Access Journals (Sweden)

    Jean-Marc Good

    2017-11-01

    Full Text Available Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF to Purkinje cell (PC network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity.

  18. Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid fatty acid composition in a muscle type specific manner in sheep

    DEFF Research Database (Denmark)

    Hou, Lei; Kongsted, Alice; Ghoreishi, S. M.

    2013-01-01

    We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key musc......, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole body insulin sensitivity in adult LOW sheep....

  19. Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

    Science.gov (United States)

    Murphy, Michelle C.; Fox, Edward A.

    2007-01-01

    The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

  20. Impaired GABAergic Inhibition in the Prefrontal Cortex of Early Postnatal Phencyclidine (PCP)-Treated Rats

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe

    2014-01-01

    A compromised ¿-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-d-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmissio...... postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life....

  1. Significance of cranial computer tomography for the early diagnosis of peri- and postnatal damage

    Energy Technology Data Exchange (ETDEWEB)

    Richter, E I

    1981-01-01

    It is reported on examination-technical possibilities with craniocerebral Computer Tomography in the peri- and postnatal period. Some typical tomographic images from a 17 1/2 months period in our own patient material of 327 children are demonstrated. The special advantages of this new technical-extensive method are: exact diagnoses, observation possibility of the longitudinal section, and the absolute harmlessness to the child.

  2. Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning.

    Science.gov (United States)

    Catlow, Briony J; Song, Shijie; Paredes, Daniel A; Kirstein, Cheryl L; Sanchez-Ramos, Juan

    2013-08-01

    Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.

  3. Sex-dependent role of vesicular glutamate transporter 3 in stress-regulation and related anxiety phenotype during the early postnatal period.

    Science.gov (United States)

    Balázsfi, Diána; Farkas, Lívia; Csikota, Péter; Fodor, Anna; Zsebők, Sándor; Haller, József; Zelena, Dóra

    2016-07-01

    Stress and related disorders are in the focus of interest and glutamate is one of the most important neurotransmitters that can affect these processes. Glutamatergic neurons are characterized by vesicular glutamate transporters (VGluT1-3) among which vGluT3 is unique contributing to the non-canonical, neuromodulatory effect of glutamate. We aimed to study the role of vGluT3 in stress axis regulation and related anxiety during the early postnatal period using knockout (KO) mice with special focus on sex differences. Anxiety was explored on postnatal day (PND) 7-8 by maternal separation-induced ultrasonic vocalization (USV). Stress-hormone levels were detected 60 min after intraperitoneal lipopolysaccharide (LPS) injection 7 days later. Both genotypes gained weight, but on PND 14-15 KO mice pups had smaller body weight compared to wild type (WT). vGluT3 KO mice reacted to an immune stressor with enhanced adrenocorticotropin (ACTH) and corticosterone secretion compared to WT. Although there was a tendency for enhanced anxiety measured by more emitted USV, this did not reach the level of significance. The only sex-related effect was the enhanced corticosterone reactivity in male pups. For the HPA axis regulation in neonates vGluT3 expression seems to be dispensable under basal conditions, but is required for optimal response to immune stressors, most probably through an interaction with other neurotransmitters. Disturbance of the fine balance between these systems may result in a borderline enhanced anxiety-like behavior in vGluT3 KO pups.

  4. Fluoxetine Regulates Neurogenesis In Vitro Through Modulation of GSK-3β/β-Catenin Signaling

    Science.gov (United States)

    Hui, Jiaojie; Zhang, Jianping; Kim, Hoon; Tong, Chang; Ying, Qilong; Li, Zaiwang; Mao, Xuqiang; Shi, Guofeng; Yan, Jie; Zhang, Zhijun

    2015-01-01

    Background: It is generally accepted that chronic treatment with antidepressants increases hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. Recently, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling was shown to be involved in the mechanism of how antidepressants might influence hippocampal neurogenesis. Methods: The aim of this study was to determine whether GSK-3β/β-catenin signaling is involved in the alteration of neurogenesis as a result of treatment with fluoxetine, a selective serotonin reuptake inhibitor. The mechanisms involved in fluoxetine’s regulation of GSK-3β/β-catenin signaling pathway were also examined. Results: Our results demonstrated that fluoxetine increased the proliferation of embryonic neural precursor cells (NPCs) by up-regulating the phosphorylation of Ser9 on GSK-3β and increasing the level of nuclear β-catenin. The overexpression of a stabilized β-catenin protein (ΔN89 β-catenin) significantly increased NPC proliferation, while inhibition of β-catenin expression in NPCs led to a significant decrease in the proliferation and reduced the proliferative effects induced by fluoxetine. The effects of fluoxetine-induced up-regulation of both phosphorylation of Ser9 on GSK-3β and nuclear β-catenin were significantly prevented by the 5-hydroxytryptamine-1A (5-HT1A) receptor antagonist WAY-100635. Conclusions: The results demonstrate that fluoxetine may increase neurogenesis via the GSK-3β/β-catenin signaling pathway that links postsynaptic 5-HT1A receptor activation. PMID:25522429

  5. In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis.

    Science.gov (United States)

    Lim, Daniel A; Suárez-Fariñas, Mayte; Naef, Felix; Hacker, Coleen R; Menn, Benedicte; Takebayashi, Hirohide; Magnasco, Marcelo; Patil, Nila; Alvarez-Buylla, Arturo

    2006-01-01

    Neural stem cells and neurogenesis persist in the adult mammalian brain subventricular zone (SVZ). Cells born in the rodent SVZ migrate to the olfactory bulb (Ob) where they differentiate into interneurons. To determine the gene expression and functional profile of SVZ neurogenesis, we performed three complementary sets of transcriptional analysis experiments using Affymetrix GeneChips: (1) comparison of adult mouse SVZ and Ob gene expression profiles with those of the striatum, cerebral cortex, and hippocampus; (2) profiling of SVZ stem cells and ependyma isolated by fluorescent-activated cell sorting (FACS); and (3) analysis of gene expression changes during in vivo SVZ regeneration after anti-mitotic treatment. Gene Ontology (GO) analysis of data from these three separate approaches showed that in adult SVZ neurogenesis, RNA splicing and chromatin remodeling are biological processes as statistically significant as cell proliferation, transcription, and neurogenesis. In non-neurogenic brain regions, RNA splicing and chromatin remodeling were not prominent processes. Fourteen mRNA splicing factors including Sf3b1, Sfrs2, Lsm4, and Khdrbs1/Sam68 were detected along with 9 chromatin remodeling genes including Mll, Bmi1, Smarcad1, Baf53a, and Hat1. We validated the transcriptional profile data with Northern blot analysis and in situ hybridization. The data greatly expand the catalogue of cell cycle components, transcription factors, and migration genes for adult SVZ neurogenesis and reveal RNA splicing and chromatin remodeling as prominent biological processes for these germinal cells.

  6. Modification of postnatal hemoglobin level and hematocrit value in the peripheral blood of mice after gamma radiation in utero by MPG (2-mercaptopropionylglycine)

    International Nuclear Information System (INIS)

    Goyal, P.K.; Kumar, S.; Dev, P.K.

    1980-01-01

    Pregnant Swiss albino mice were irradiated with oamma radiation at post-conception days 14.5, 16.25 and 18.25. Hemoglobin level and hematocrit value in the peripheral blood of the male offsprings were found to be below normal during the early postnatal development. The value became normal from 4 week onwards. However these values were found to be significantly elevated in the early postnatal development of the male offsprings of the mice which were administered MPG before irradiation. The possible radioprotective mechanism of MPG is discussed. (M.G.B.)

  7. Spatial learning and memory deficits in young adult mice exposed to a brief intense noise at postnatal age

    Institute of Scientific and Technical Information of China (English)

    Shan Tao; Lijie Liu; Lijuan Shi; Xiaowei Li; Pei Shen; Qingying Xun; Xiaojing Guo; Zhiping Yu; Jian Wang

    2015-01-01

    Noise pollution is a major hazardous factor to human health and is likely harmful for vulnerable groups such as pre-term infants under life-support system in an intensive care unit. Previous studies have suggested that noise exposure impairs children's learning ability and cognitive performance and cognitive functions in animal models in which the effect is mainly attributed to the oxidant stress of noise on the cognitive brain. The potential role of noise induced hearing loss (NIHL), rather than the oxidant stress, has also been indicated by a depression of neurogenesis in the hippocampus long after a brief noise exposure, which produces only a tentative oxidant stress. It is not clear if noise exposure and NIHL during early development exerts a long term impact on cognitive function and neurogenesis towards adulthood. In the present study, a brief noise exposure at high sound level was performed in neonatal C57BL/6J mice (15 days after birth) to produce a significant amount of permanent hearing loss as proved 2 months after the noise. At this age, the noise-exposed animals showed deteriorated spatial learning and memory abilities and a reduction of hippocampal neurogenesis as compared with the control. The averaged hearing threshold was found to be strongly correlated with the scores for spatial learning and memory. We consider the effects observed are largely due to the loss of hearing sensitivity, rather than the oxidant stress, due to the long interval between noise exposure and the observations.

  8. Delayed and transient increase of adult hippocampal neurogenesis by physical exercise in DBA/2 mice.

    Directory of Open Access Journals (Sweden)

    Rupert W Overall

    Full Text Available This study builds on the findings that physical activity, such as wheel running in mice, enhances cell proliferation and neurogenesis in the adult hippocampus of the common mouse strain C57BL/6, and that the baseline level of neurogenesis varies by strain, being considerably lower in DBA/2. Because C57BL/6 and DBA/2 are important as the parental strains of the BXD recombinant inbred cross which allows the detection of genetic loci regulating phenotypes such as adult neurogenesis, we performed the current study to investigate the gene x environment interactions regulating neurogenesis. At equal distances and times run DBA/2J mice lacked the acute increase in precursor cell proliferation known from C57BL/6. In DBA/2J proliferation even negatively correlated with the distance run. This was neither due to a stress response (to running itself or single housing nor differences in estrous cycle. DBA/2 animals exhibited a delayed and weaker pro-neurogenic response with a significant increase in numbers of proliferating cells first detectable after more than a week of wheel running. The proliferative response to running was transient in both strains, the effect being undetectable by 6 weeks. There was also a small transient increase in the production of new neurons in DBA/2J, although these extra cells did not survive. These findings indicate that the comparison between C57BL/6 and DBA/2, and by extension the BXD genetic reference population derived from these strains, should provide a powerful tool for uncovering the complex network of modifier genes affecting the activity-dependent regulation of adult hippocampal neurogenesis. More generally, our findings also describe how the external physical environment interacts with the internal genetic environment to produce different responses to the same behavioral stimuli.

  9. BET bromodomain inhibition promotes neurogenesis while inhibiting gliogenesis in neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Jingjun Li

    2016-09-01

    Full Text Available Neural stem cells and progenitor cells (NPCs are increasingly appreciated to hold great promise for regenerative medicine to treat CNS injuries and neurodegenerative diseases. However, evidence for effective stimulation of neuronal production from endogenous or transplanted NPCs for neuron replacement with small molecules remains limited. To identify novel chemical entities/targets for neurogenesis, we had established a NPC phenotypic screen assay and validated it using known small-molecule neurogenesis inducers. Through screening small molecule libraries with annotated targets, we identified BET bromodomain inhibition as a novel mechanism for enhancing neurogenesis. BET bromodomain proteins, Brd2, Brd3, and Brd4 were found to be downregulated in NPCs upon differentiation, while their levels remain unaltered in proliferating NPCs. Consistent with the pharmacological study using bromodomain selective inhibitor (+-JQ-1, knockdown of each BET protein resulted in an increase in the number of neurons with simultaneous reduction in both astrocytes and oligodendrocytes. Gene expression profiling analysis demonstrated that BET bromodomain inhibition induced a broad but specific transcription program enhancing directed differentiation of NPCs into neurons while suppressing cell cycle progression and gliogenesis. Together, these results highlight a crucial role of BET proteins as epigenetic regulators in NPC development and suggest a therapeutic potential of BET inhibitors in treating brain injuries and neurodegenerative diseases.

  10. Parental experiences of early postnatal discharge

    DEFF Research Database (Denmark)

    Nilsson, Ingrid; Danbjørg, Dorthe B.; Aagaard, Hanne

    2015-01-01

    that included both parents, having influence on time of discharge, and getting individualised and available support focused on developing and recognising their own experiences of taking care of the baby. Conclusions and implications for practice the new parents׳ experiences of early discharge and becoming...

  11. Uptake and predictors of early postnatal follow-up care amongst mother-baby pairs in South Africa: Results from three population-based surveys, 2010-2013.

    Science.gov (United States)

    Larsen, Anna; Cheyip, Mireille; Aynalem, Getahun; Dinh, Thu-Ha; Jackson, Debra; Ngandu, Nobubelo; Chirinda, Witness; Mogashoa, Mary; Kindra, Gupreet; Lombard, Carl; Goga, Ameena

    2017-12-01

    Achieving World Health Organization (WHO) recommendations for postnatal care (PNC) within the first few weeks of life is vital to eliminating early mother-to-child transmission of HIV (MTCT) and improving infant health. Almost half of the annual global deaths among children under five occur during the first six weeks of life. This study aims to identify uptake of three PNC visits within the first six weeks of life as recommended by WHO among South African mother-infant pairs, and factors associated with uptake. We analyzed data from three facility-based, nationally representative surveys (2010, 2011/12 and 2012/13) primarily designed to determine the effectiveness of the South African program to prevent MTCT. This analysis describes the proportion of infants achieving the WHO recommendation of at least 3 PNC visits. Interviews from 27 699 HIV-negative and HIV-positive mothers of infants aged 4-8 weeks receiving their six week immunization were included in analysis. Data were analyzed using STATA 13.0 and weighted for sample ascertainment and South African live births. We fitted a multivariable logistic regression model to estimate factors associated with early PNC uptake. Over half (59.6%, 95% confidence interval (CI) = 59.0-60.3) of mother-infant pairs received the recommended three PNC visits during the first 6 weeks; uptake was 63.1% (95% CI = 61.9-64.3) amongst HIV exposed infants and 58.1% (95% CI = 57.3-58.9) amongst HIV unexposed infants. Uptake of early PNC improved significantly with each survey, but varied significantly by province. Multivariable analysis of the pooled data, controlling for survey year, demonstrated that number of antenatal visits (4+ vs 12 weeks, aOR = 1.13, 95% CI = 1.04-1.23), place of delivery (clinic vs hospital aOR = 1.5, 1.3-1.6), and infant HIV exposure (exposed vs unexposed aOR = 1.2, 95% CI = 1.1-1.2) were the key factors associated with receiving recommended PNC visits. Approximately 40% of

  12. From network structure to network reorganization: implications for adult neurogenesis

    International Nuclear Information System (INIS)

    Schneider-Mizell, Casey M; Zochowski, Michal R; Sander, Leonard M; Parent, Jack M; Ben-Jacob, Eshel

    2010-01-01

    Networks can be dynamical systems that undergo functional and structural reorganization. One example of such a process is adult hippocampal neurogenesis, in which new cells are continuously born and incorporate into the existing network of the dentate gyrus region of the hippocampus. Many of these introduced cells mature and become indistinguishable from established neurons, joining the existing network. Activity in the network environment is known to promote birth, survival and incorporation of new cells. However, after epileptogenic injury, changes to the connectivity structure around the neurogenic niche are known to correlate with aberrant neurogenesis. The possible role of network-level changes in the development of epilepsy is not well understood. In this paper, we use a computational model to investigate how the structural and functional outcomes of network reorganization, driven by addition of new cells during neurogenesis, depend on the original network structure. We find that there is a stable network topology that allows the network to incorporate new neurons in a manner that enhances activity of the persistently active region, but maintains global network properties. In networks having other connectivity structures, new cells can greatly alter the distribution of firing activity and destroy the initial activity patterns. We thus find that new cells are able to provide focused enhancement of network only for small-world networks with sufficient inhibition. Network-level deviations from this topology, such as those caused by epileptogenic injury, can set the network down a path that develops toward pathological dynamics and aberrant structural integration of new cells

  13. Omega-3 fatty acids upregulate adult neurogenesis

    OpenAIRE

    Beltz, Barbara S.; Tlusty, Michael F.; Benton, Jeannie L.; Sandeman, David C.

    2007-01-01

    Omega-3 fatty acids play crucial roles in the development and function of the central nervous system. These components, which must be obtained from dietary sources, have been implicated in a variety of neurodevelopmental and psychiatric disorders. Furthermore, the presence of omega-6 fatty acids may interfere with omega-3 fatty acid metabolism. The present study investigated whether changes in dietary ratios of omega-3:omega-6 fatty acids influence neurogenesis in the lobster (Homarus america...

  14. ACTIONS OF PROLACTIN IN THE BRAIN: FROM PHYSIOLOGICAL ADAPTATIONS TO STRESS AND NEUROGENESIS TO PSYCHOPATHOLOGY

    Directory of Open Access Journals (Sweden)

    Luz eTorner

    2016-03-01

    Full Text Available Prolactin is one of the most versatile hormones known. It is considered an adaptive hormone due to the key roles it plays in the modulation of the stress response and during pregnancy and lactation. Within the brain, prolactin acts as a neuropeptide to promote physiological responses related to reproduction, stress adaptation, neurogenesis, and neuroprotection. The action of prolactin on the nervous system contributes to the wide array of changes that occur in the female brain during pregnancy and result in the attenuation of the hypothalamic pituitary adrenal axis. Together, all these changes promote behavioral and physiological adaptations of the new mother to enable reproductive success. Brain adaptations driven by prolactin are also important for the regulation of maternal emotionality and wellbeing Prolactin also affects the male brain during the stress response but its effects have been less studied. Prolactin regulates neurogenesis both in the subventricular zone and in the hippocampus. Therefore, alterations in the prolactin system due to stress, or exposure to substances that reduce neurogenesis or other conditions, could contribute to maladaptive responses and pathological behavioral outcomes. Here we review the prolactin system and the role it plays in the modulation of stress response and emotion regulation. We discuss the effects of prolactin on neurogenesis and neuroprotection, the putative neuronal mechanisms underlying these effects, and their contribution to the onset of psychopathological states like depression.

  15. Circadian Clock Genes Are Essential for Normal Adult Neurogenesis, Differentiation, and Fate Determination.

    Directory of Open Access Journals (Sweden)

    Astha Malik

    Full Text Available Adult neurogenesis creates new neurons and glia from stem cells in the human brain throughout life. It is best understood in the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ. Circadian rhythms have been identified in the hippocampus, but the role of any endogenous circadian oscillator cells in hippocampal neurogenesis and their importance in learning or memory remains unclear. Any study of stem cell regulation by intrinsic circadian timing within the DG is complicated by modulation from circadian clocks elsewhere in the brain. To examine circadian oscillators in greater isolation, neurosphere cultures were prepared from the DG of two knockout mouse lines that lack a functional circadian clock and from mPer1::luc mice to identify circadian oscillations in gene expression. Circadian mPer1 gene activity rhythms were recorded in neurospheres maintained in a culture medium that induces neurogenesis but not in one that maintains the stem cell state. Although the differentiating neural stem progenitor cells of spheres were rhythmic, evidence of any mature neurons was extremely sparse. The circadian timing signal originated in undifferentiated cells within the neurosphere. This conclusion was supported by immunocytochemistry for mPER1 protein that was localized to the inner, more stem cell-like neurosphere core. To test for effects of the circadian clock on neurogenesis, media conditions were altered to induce neurospheres from BMAL1 knockout mice to differentiate. These cultures displayed unusually high differentiation into glia rather than neurons according to GFAP and NeuN expression, respectively, and very few BetaIII tubulin-positive, immature neurons were observed. The knockout neurospheres also displayed areas visibly devoid of cells and had overall higher cell death. Neurospheres from arrhythmic mice lacking two other core clock genes, Cry1 and Cry2, showed significantly reduced growth and increased astrocyte

  16. Postnatal growth standards for preterm infants: the Preterm Postnatal Follow-up Study of the INTERGROWTH-21(st) Project.

    Science.gov (United States)

    Villar, José; Giuliani, Francesca; Bhutta, Zulfiqar A; Bertino, Enrico; Ohuma, Eric O; Ismail, Leila Cheikh; Barros, Fernando C; Altman, Douglas G; Victora, Cesar; Noble, Julia A; Gravett, Michael G; Purwar, Manorama; Pang, Ruyan; Lambert, Ann; Papageorghiou, Aris T; Ochieng, Roseline; Jaffer, Yasmin A; Kennedy, Stephen H

    2015-11-01

    Charts of size at birth are used to assess the postnatal growth of preterm babies on the assumption that extrauterine growth should mimic that in the uterus. The INTERGROWTH-21(st) Project assessed fetal, newborn, and postnatal growth in eight geographically defined populations, in which maternal health care and nutritional needs were met. From these populations, the Fetal Growth Longitudinal Study selected low-risk women starting antenatal care before 14 weeks' gestation and monitored fetal growth by ultrasonography. All preterm births from this cohort were eligible for the Preterm Postnatal Follow-up Study, which included standardised anthropometric measurements, feeding practices based on breastfeeding, and data on morbidity, treatments, and development. To construct the preterm postnatal growth standards, we selected all live singletons born between 26 and before 37 weeks' gestation without congenital malformations, fetal growth restriction, or severe postnatal morbidity. We did analyses with second-degree fractional polynomial regression models in a multilevel framework accounting for repeated measures. Fetal and neonatal data were pooled from study sites and stratified by postmenstrual age. For neonates, boys and girls were assessed separately. From 4607 women enrolled in the study, there were 224 preterm singleton births, of which 201 (90%) were enrolled in the Preterm Postnatal Follow-up Study. Variance component analysis showed that only 0·2% and 4·0% of the total variability in postnatal length and head circumference, respectively, could be attributed to between-site differences, justifying pooling the data from all study sites. Preterm growth patterns differed from those for babies in the INTERGROWTH-21(st) Newborn Size Standards. They overlapped with the WHO Child Growth Standards for term babies by 64 weeks' postmenstrual age. Our data have yielded standards for postnatal growth in preterm infants. These standards should be used for the assessment of

  17. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Directory of Open Access Journals (Sweden)

    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  18. Defensive behaviors and prosencephalic neurogenesis in pigeons (Columba livia) are affected by environmental enrichment in adulthood.

    Science.gov (United States)

    Melleu, F F; Pinheiro, M V; Lino-de-Oliveira, C; Marino-Neto, J

    2016-05-01

    Neurogenesis in the adult brain appears to be phylogenetically conserved across the animal kingdom. In pigeons and other adult non-oscine birds, immature neurons are observed in several prosencephalic areas, suggesting that neurogenesis may participate in the control of different behaviors. The mechanisms controlling neurogenesis and its relevance to defensive behaviors in non-oscine birds remain elusive. Herein, the contribution of the environment to behavior and neurogenesis of pigeons was investigated. Adult pigeons (Columba livia, n = 6/group), housed in standard (SE) or enriched environment (EE) for 42 days, were exposed to an unfamiliar environment (UE) followed by presentation to a novel object (NO). Video recordings of UE+NO tests were analyzed and scored for latency, duration and frequency of angular head movements, peeping, grooming, immobility and locomotion. Twenty-four hours later, pigeons were submitted to the tonic immobility test (TI) and number of trials for TI and TI duration were scored, followed by euthanasia 2 h later. Brains were immunohistochemically processed to reveal doublecortin (DCX), a marker for newborn neurons. Compared to those housed in SE, the pigeons housed in EE responded to a NO with more immobility. In addition, the pigeons housed in EE presented longer TI, more DCX-immunoreactive (DCX-ir) cells in the hippocampus and fewer DCX-ir cells in the lateral striatum than those housed in SE. There was no correlation between the number of DCX-ir cells and the scores of immobility in behavioral tests. Together, these data suggest that enrichment favored behavioral inhibition and neurogenesis in the adult pigeons through different, parallel mechanisms.

  19. The endogenous regenerative capacity of the damaged newborn brain: boosting neurogenesis with mesenchymal stem cell treatment.

    Science.gov (United States)

    Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; Kavelaars, Annemieke; Heijnen, Cobi J

    2013-05-01

    Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxia-ischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategies. The latest findings indicate that stem cells represent a novel therapeutic possibility to improve outcome in models of neonatal encephalopathy. Transplanted stem cells secrete factors that stimulate and maintain neurogenesis, thereby increasing cell proliferation, neuronal differentiation, and functional integration. Understanding the molecular and cellular mechanisms underlying neurogenesis after an insult is crucial for developing tools to enhance the neurogenic capacity of the brain. The aim of this review is to discuss the endogenous capacity of the neonatal brain to regenerate after a cerebral ischemic insult. We present an overview of the molecular and cellular mechanisms underlying endogenous regenerative processes during development as well as after a cerebral ischemic insult. Furthermore, we will consider the potential to use stem cell transplantation as a means to boost endogenous neurogenesis and restore brain function.

  20. Bad thoughts: Brazilian women's responses to mothering while experiencing postnatal depression.

    Science.gov (United States)

    Santos, Hudson Pires Oliveira; Sandelowski, Margarete; Gualda, Dulce Maria Rosa

    2014-06-01

    this study explores Brazilian women's experiences of mothering of their infants while experiencing postnatal depression. a cross-language qualitative descriptive design. the sample was composed of 15 women diagnosed with postnatal depression in a psychiatric institute in São Paulo, Brazil. Open-ended interviews were conducted and the data underwent thematic analysis. 13 women worried that harm would come to their infants. Seven of these women self-identified as potential sources of harm, with two women physically hurting their infants. The remaining six women worried about unknown agents, such as disease, hurting their infants. In response to these bad thoughts, women mothered their infants in one of four ways: (1) transferred care, completely delegating this task to family members; (2) shared care, asking family members to share the responsibility; (3) sole care, having to look after their infants by themselves because they had no available family support; (4) and smother care, being hyper-vigilant, constantly watching their infants and not trusting infant care to anyone else. the bad thoughts influenced the women's adaptation to mothering their infants. Health professionals should assess these thoughts early in the postnatal period and the women's mothering responses for the protection of mother and child. © 2013 Published by Elsevier Ltd.

  1. Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition.

    Science.gov (United States)

    Meyers, Emily A; Gobeske, Kevin T; Bond, Allison M; Jarrett, Jennifer C; Peng, Chian-Yu; Kessler, John A

    2016-02-01

    Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The role of additive neurogenesis and synaptic plasticity in a hippocampal memory model with grid-cell like input.

    Directory of Open Access Journals (Sweden)

    Peter A Appleby

    Full Text Available Recently, we presented a study of adult neurogenesis in a simplified hippocampal memory model. The network was required to encode and decode memory patterns despite changing input statistics. We showed that additive neurogenesis was a more effective adaptation strategy compared to neuronal turnover and conventional synaptic plasticity as it allowed the network to respond to changes in the input statistics while preserving representations of earlier environments. Here we extend our model to include realistic, spatially driven input firing patterns in the form of grid cells in the entorhinal cortex. We compare network performance across a sequence of spatial environments using three distinct adaptation strategies: conventional synaptic plasticity, where the network is of fixed size but the connectivity is plastic; neuronal turnover, where the network is of fixed size but units in the network may die and be replaced; and additive neurogenesis, where the network starts out with fewer initial units but grows over time. We confirm that additive neurogenesis is a superior adaptation strategy when using realistic, spatially structured input patterns. We then show that a more biologically plausible neurogenesis rule that incorporates cell death and enhanced plasticity of new granule cells has an overall performance significantly better than any one of the three individual strategies operating alone. This adaptation rule can be tailored to maximise performance of the network when operating as either a short- or long-term memory store. We also examine the time course of adult neurogenesis over the lifetime of an animal raised under different hypothetical rearing conditions. These growth profiles have several distinct features that form a theoretical prediction that could be tested experimentally. Finally, we show that place cells can emerge and refine in a realistic manner in our model as a direct result of the sparsification performed by the dentate gyrus

  3. The male sex pheromone darcin stimulates hippocampal neurogenesis and cell proliferation in the subventricular zone in female mice

    Directory of Open Access Journals (Sweden)

    Emma eHoffman

    2015-04-01

    Full Text Available The integration of newly generated neurons persists throughout life in the mammalian olfactory bulb and hippocampus, regions involved in olfactory and spatial learning. Social cues can be potent stimuli for increasing adult neurogenesis; for example, odors from dominant but not subordinate male mice increase neurogenesis in both brain regions of adult females. However, little is known about the role of neurogenesis in social recognition or the assessment of potential mates. Dominant male mice scent-mark territories using urine that contains a number of pheromones including darcin (MUP20, a male-specific major urinary protein that stimulates rapid learned attraction to the spatial location and individual odor signature of the scent owner. Here we investigate whether exposure to darcin stimulates neurogenesis in the female brain. Hippocampal neurons and cellular proliferation in the lateral ventricles that supply neurons to the olfactory bulbs increased in females exposed for seven days to male urine containing at least 0.5µg/µl darcin. Darcin was effective whether presented alone or in the context of male urine, but other information in male urine appeared to modulate the proliferative response. When exposed to urine from wild male mice, hippocampal proliferation increased only if urine was from the same individual over seven days, suggesting that consistency of individual scent signatures is important. While seven days exposure to male scent initiated the first stages of increased neurogenesis, this caused no immediate increase in female attraction to the scent or in the strength or robustness of spatial learning in short-term conditioned place preference tests. The reliable and consistent stimulation of neurogenesis by a pheromone important in rapid social learning suggests that this may provide an excellent model to explore the relationship between the integration of new neurons and plasticity in spatial and olfactory learning in a socially

  4. Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life.

    Science.gov (United States)

    Velazquez, Miguel A; Sheth, Bhavwanti; Smith, Stephanie J; Eckert, Judith J; Osmond, Clive; Fleming, Tom P

    2018-02-01

    Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to examine the consequences for blastocyst organisation and, after embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to blastocyst stage in defined KSOM medium supplemented with four combinations of insulin and BCAA concentrations. Control medium contained serum insulin and uterine luminal fluid amino acid concentrations (including BCAA) found in control mothers from the maternal diet model (N-insulin+N-bcaa). Experimental medium (three groups) contained 50% reduction in insulin and/or BCAA (L-insulin+N-bcaa, N-insulin+L-bcaa, and L-insulin+N-bcaa). Lineage-specific cell numbers of resultant blastocysts were not affected by treatment. Following ET, a combined depletion of insulin and BCAA during embryo culture induced a non sex-specific increase in birth weight and weight gain during early postnatal life. Furthermore, male offspring displayed relative hypertension and female offspring reduced heart/body weight, both characteristics of Emb-LPD offspring. Combined depletion of metabolites also resulted in a strong positive correlation between body weight and glucose metabolism that was absent in the control group. Our results support the notion that composition of preimplantation culture medium can programme development and associate with disease origin affecting postnatal growth and cardiovascular phenotypes and implicate two important nutritional mediators in the inductive mechanism. Our data also have implications for human assisted reproductive treatment (ART) practice. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant's immune system early in life.

    Science.gov (United States)

    Richard, Caroline; Lewis, Erin D; Field, Catherine J

    2016-05-01

    Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.

  6. Oncolytic effects of parvovirus H-1 in medulloblastoma are associated with repression of master regulators of early neurogenesis.

    Science.gov (United States)

    Lacroix, Jeannine; Schlund, Franziska; Leuchs, Barbara; Adolph, Kathrin; Sturm, Dominik; Bender, Sebastian; Hielscher, Thomas; Pfister, Stefan M; Witt, Olaf; Rommelaere, Jean; Schlehofer, Jörg R; Witt, Hendrik

    2014-02-01

    Based on extensive pre-clinical studies, the oncolytic parvovirus H-1 (H-1PV) is currently applied to patients with recurrent glioblastoma in a phase I/IIa clinical trial (ParvOryx01, NCT01301430). Cure rates of about 40% in pediatric high-risk medulloblastoma (MB) patients also indicate the need of new therapeutic approaches. In order to prepare a future application of oncolytic parvovirotherapy to MB, the present study preclinically evaluates the cytotoxic efficacy of H-1PV on MB cells in vitro and characterizes cellular target genes involved in this effect. Six MB cell lines were analyzed by whole genome oligonucleotide microarrays after treatment and the results were matched to known molecular and cytogenetic risk factors. In contrast to non-transformed infant astrocytes and neurons, in five out of six MB cell lines lytic H-1PV infection and efficient viral replication could be demonstrated. The cytotoxic effects induced by H-1PV were observed at LD50s below 0.05 p. f. u. per cell indicating high susceptibility. Gene expression patterns in the responsive MB cell lines allowed the identification of candidate target genes mediating the cytotoxic effects of H-1PV. H-1PV induced down-regulation of key regulators of early neurogenesis shown to confer poor prognosis in MB such as ZIC1, FOXG1B, MYC, and NFIA. In MB cell lines with genomic amplification of MYC, expression of MYC was the single gene most significantly repressed after H-1PV infection. H-1PV virotherapy may be a promising treatment approach for MB since it targets genes of functional relevance and induces cell death at very low titers of input virus. Copyright © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  7. Endurance Factors Improve Hippocampal Neurogenesis and Spatial Memory in Mice

    Science.gov (United States)

    Kobilo, Tali; Yuan, Chunyan; van Praag, Henriette

    2011-01-01

    Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor [delta] agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and…

  8. Early determinants of mental health

    NARCIS (Netherlands)

    Räikkönen, Katri; Pesonen, Anu-Katriina; Roseboom, Tessa J.; Eriksson, Johan G.

    2012-01-01

    Environmental adversities in pre- and early postnatal life may have life-long consequences. Based upon a series of epidemiological and clinical studies and natural experiments, this review describes how the early life environment may affect psychological functions and mental disorders later in life.

  9. Postnatal events in intestinal gene expression and splenic cell composition is altered in NOD mice

    DEFF Research Database (Denmark)

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Kristensen, Matilde Bylov

    2013-01-01

    microbiota seems to play an important role in the development and control of T1D. We hypothesized that NOD mice in the perinatal period respond differently than mice not prone to develop T1D (C57/Bl6), and we investigated the differences in postnatal expression of genes in gut, spleen, liver and pancreas......Evidence suggests that colonisation pattern of the gut in the early postnatal period is highly correlated with the risk of developing type 1 diabetes (T1D). We have recently shown that colonization in SPF mice accelerates gut maturation and that at postnatal day (PND) 1, in comparison with germ...... free mice, certain chemokines, including Cxcl2 encoding macrophage inflammatory protein (MIP)-2 and involved in attraction of neutrophils was downregulated in the gut epithelium. The non-obese diabetes (NOD) mouse is widely used as a model for studying the pathogenesis of T1D. The neonatal gut...

  10. The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders

    DEFF Research Database (Denmark)

    Bonde, Jens Peter; Flachs, Esben Meulengracht; Rimborg, Susie

    2017-01-01

    BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several con...

  11. Factors associated with lack of postnatal care among Palestinian women: A cross-sectional study of three clinics in the West Bank

    Directory of Open Access Journals (Sweden)

    Maxwell Annette E

    2008-07-01

    Full Text Available Abstract Background Only about one-third of women in Palestine (West Bank and Gaza obtain postpartum care. Therefore, the goal of this study was to assess factors associated with lack of postnatal care, women's reasons for not obtaining postnatal care, and their attitudes towards its importance. Methods In early 2006, a cross-sectional survey was conducted at three clinics run by the Ministry of Health providing Mother and Child Health Care in West Bank, Palestine. A total of 264 postpartum women attending the clinics were interviewed face-to-face, using a structured questionnaire. Results Although the majority of women considered postnatal care necessary (66.1%, only 36.6% of women obtained postnatal care. The most frequent reason for not obtaining postnatal care was that women did not feel sick and therefore did not need postnatal care (85%, followed by not having been told by their doctor to come back for postnatal care (15.5%. Based on a multivariable analysis, use of postnatal care was higher among women who had experienced problems during their delivery, had a cesarean section, or had an instrumental vaginal delivery than among women who had a spontaneous vaginal delivery. Use of postnatal care was also higher among women who delivered in a private hospital as compared to those who delivered in a public hospital. In addition, we found regional differences. Conclusion The higher use of postnatal care among high-risk women is appropriate, but some clinically dangerous conditions can also occur in low-risk women. Future efforts should therefore focus on providing postnatal care to a larger number of low-risk women.

  12. Adult hippocampal neurogenesis and cognitive aging

    Directory of Open Access Journals (Sweden)

    Román Darío Moreno Fernández

    2013-12-01

    Full Text Available Aging is a normal developmental process associated with neurobiological changes leading to cognitive alterations with preserved, impaired, and enhanced functions. Evidence from animal and human studies is reviewed to explore the potential role of hippocampal plasticity on age-related cognitive changes with special attention to adult hippocampal neurogenesis. Results from lesion and stimulation strategies, as well as correlation data, support either a direct or modulatory role for adult newborn neurons in cognition at advanced ages. Further research on this topic may help to develop new treatments and to improve the quality of life of older people.

  13. Impact of trichostatin A and sodium valproate treatment on post-stroke neurogenesis and behavioral outcomes in immature mice

    Directory of Open Access Journals (Sweden)

    Shanu eGeorge

    2013-08-01

    Full Text Available Stroke in the neonatal brain frequently results in neurologic impairments including cognitive disability. We investigated the effect of long-term sodium valproate (valproate and Trichostatin A (TSA treatment upon post-stroke neurogenesis in the dentate gyrus (DG of stroke-injured immature mice. Decreased or abnormal integration of newborn DG neurons into hippocampal circuits can result in impaired visual-spatial function, abnormal modulation of mood-related behaviors, and the development of post-stroke epilepsy. Unilateral carotid ligation of P12 CD1 mice was followed by treatment with valproate, TSA, or vehicle for 2 weeks, BrdU administration for measurement of neurogenesis, and perfusion at P42 or P60. Behavior testing was conducted from P38-42. No detrimental effects on behavior testing were noted with TSA treatment, but mildly impaired cognitive function was noted with valproate-treated injured animals compared to normal animals. Significant increases in DG neurogenesis with both TSA and valproate treatment were noted with later administration of BrdU. Increased mortality and impaired weight gain was noted in the valproate-treated ligated animals, but not in the TSA-treated animals. In summary, the impact of HDAC inhibition upon post-stroke SGZ neurogenesis is likely to depend on the age of the animal at the time point when neurogenesis is assessed, duration of HDAC inhibition before BrdU labeling, and/or the stage in the evolution of the injury.

  14. Unbiased cell quantification reveals a continued increase in the number of neocortical neurones during early post-natal development in mice

    DEFF Research Database (Denmark)

    Lyck, Lise; Krøigård, Thomas; Finsen, Bente

    2007-01-01

    The post-natal growth spurt of the mammalian neocortex has been attributed to maturation of dendritic arborizations, growth and myelination of axons, and addition of glia. It is unclear whether this growth may also involve recruitment of additional neurones. Using stereological methods, we analysed...... the number of neurones and glia in the neocortex during post-natal development in two separate strains of mice. Cell counting by the optical fractionator revealed that the number of neurones increased 80-100% from the time of birth to post-natal day (P)16, followed by a reduction by approximately 25...... was delayed until P16. The number of glia reached its maximum at P16, whereas the number of oligodendroglia, identified using a transgenic marker, increased until P55, the latest time of observation. Neurones continued to accumulate in the developing neocortex during the first 2 weeks of post...

  15. Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review.

    Science.gov (United States)

    Kingston, Dawn; McDonald, Sheila; Austin, Marie-Paule; Tough, Suzanne

    2015-01-01

    Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development. Articles were included if: a) they were observational studies published in English; b) the exposure was prenatal or postnatal psychological distress; c) cognitive development was assessed from 13 to 36 months; d) the sample was recruited in developed countries; and e) exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline) (January, 1990-March, 2014). We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form. Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes. Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development.

  16. Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Dawn Kingston

    Full Text Available Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development.Articles were included if: a they were observational studies published in English; b the exposure was prenatal or postnatal psychological distress; c cognitive development was assessed from 13 to 36 months; d the sample was recruited in developed countries; and e exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline (January, 1990-March, 2014. We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form.Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes.Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development.

  17. Neurogenesis in the septal and temporal part of the adult rat dentate gyrus.

    Science.gov (United States)

    Bekiari, Chryssa; Giannakopoulou, Aggeliki; Siskos, Nikistratos; Grivas, Ioannis; Tsingotjidou, Anastasia; Michaloudi, Helen; Papadopoulos, Georgios C

    2015-04-01

    Structural and functional dissociation between the septal and the temporal part of the dentate gyrus predispose for possible differentiations in the ongoing neurogenesis process of the adult hippocampus. In this study, BrdU-dated subpopulations of the rat septal and temporal dentate gyrus (coexpressing GFAP, DCX, NeuN, calretinin, calbindin, S100, caspase-3 or fractin) were quantified comparatively at 2, 5, 7, 14, 21, and 30 days after BrdU administration in order to examine the successive time-frames of the neurogenesis process, the glial or neuronal commitment of newborn cells and the occurring apoptotic cell death. Newborn neurons' migration from the neurogenic subgranular zone to the inner granular cell layer and expression of glutamate NMDA and AMPA receptors were also studied. BrdU immunocytochemistry revealed comparatively higher numbers of BrdU(+) cells in the septal part, but stereological analysis of newborn and total granule cells showed an identical ratio in the two parts, indicating an equivalent neurogenic ability, and a common topographical pattern along each part's longitudinal and transverse axis. Similarly, both parts exhibited extremely low levels of newborn glial and apoptotic cells. However, despite the initially equal division rate and pattern of the septal and temporal proliferating cells, their later proliferative profile diverged in the two parts. Dynamic differences in the differentiation, migration and maturation process of the two BrdU-incorporating subpopulations of newborn neurons were also detected, along with differences in their survival pattern. Therefore, we propose that various factors, including developmental date birth, local DG microenvironment and distinct functionality of the two parts may be the critical regulators of the ongoing neurogenesis process, leading the septal part to a continuous, rapid, and less-disciplined genesis rate, whereas the quiescent temporal microenvironment preserves a quite steady, less

  18. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

    Science.gov (United States)

    Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michèle; Alfano, Christian

    2016-01-01

    During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. DOI: http://dx.doi.org/10.7554/eLife.09531.001 PMID:26814051

  19. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease

    International Nuclear Information System (INIS)

    Tang, Jun; Song, Min; Wang, Yanyan; Fan, Xiaotang; Xu, Haiwei; Bai, Yun

    2009-01-01

    In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP swe /PS1 ΔE9 mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP swe /PS1 ΔE9 transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

  20. A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Broberg, Brian V; Madsen, Kristoffer H; Plath, Niels

    2013-01-01

    administration of phencyclidine (PCP) induces schizophrenia-like symptoms in healthy volunteers and exacerbates symptoms in patients with schizophrenia. In this study, pharmacological Magnetic Resonance Imaging (phMRI) was used to evaluate if rats treated with 20mg/kg PCP on postnatal days 7, 9, and 11 (neo...

  1. Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia.

    Science.gov (United States)

    Moraga, Ana; Pradillo, Jesús M; García-Culebras, Alicia; Palma-Tortosa, Sara; Ballesteros, Ivan; Hernández-Jiménez, Macarena; Moro, María A; Lizasoain, Ignacio

    2015-05-10

    Aging is not just a risk factor of stroke, but it has also been associated with poor recovery. It is known that stroke-induced neurogenesis is reduced but maintained in the aged brain. However, there is no consensus on how neurogenesis is affected after stroke in aged animals. Our objective is to determine the role of aging on the process of neurogenesis after stroke. We have studied neurogenesis by analyzing proliferation, migration, and formation of new neurons, as well as inflammatory parameters, in a model of cerebral ischemia induced by permanent occlusion of the middle cerebral artery in young- (2 to 3 months) and middle-aged mice (13 to 14 months). Aging increased both microglial proliferation, as shown by a higher number of BrdU(+) cells and BrdU/Iba1(+) cells in the ischemic boundary and neutrophil infiltration. Interestingly, aging increased the number of M1 monocytes and N1 neutrophils, consistent with pro-inflammatory phenotypes when compared with the alternative M2 and N2 phenotypes. Aging also inhibited (subventricular zone) SVZ cell proliferation by decreasing both the number of astrocyte-like type-B (prominin-1(+)/epidermal growth factor receptor (EGFR)(+)/nestin(+)/glial fibrillary acidic protein (GFAP)(+) cells) and type-C cells (prominin-1(+)/EGFR(+)/nestin(-)/Mash1(+) cells), and not affecting apoptosis, 1 day after stroke. Aging also inhibited migration of neuroblasts (DCX(+) cells), as indicated by an accumulation of neuroblasts at migratory zones 14 days after injury; consistently, aged mice presented a smaller number of differentiated interneurons (NeuN(+)/BrdU(+) and GAD67(+) cells) in the peri-infarct cortical area 14 days after stroke. Our data confirm that stroke-induced neurogenesis is maintained but reduced in aged animals. Importantly, we now demonstrate that aging not only inhibits proliferation of specific SVZ cell subtypes but also blocks migration of neuroblasts to the damaged area and decreases the number of new interneurons in

  2. Intermittent fasting attenuates increases in neurogenesis after ischemia and reperfusion and improves recovery.

    Science.gov (United States)

    Manzanero, Silvia; Erion, Joanna R; Santro, Tomislav; Steyn, Frederik J; Chen, Chen; Arumugam, Thiruma V; Stranahan, Alexis M

    2014-05-01

    Intermittent fasting (IF) is neuroprotective across a range of insults, but the question of whether extending the interval between meals alters neurogenesis after ischemia remains unexplored. We therefore measured cell proliferation, cell death, and neurogenesis after transient middle cerebral artery occlusion (MCAO) or sham surgery (SHAM) in mice fed ad libitum (AL) or maintained on IF for 3 months. IF was associated with twofold reductions in circulating levels of the adipocyte cytokine leptin in intact mice, but also prevented further reductions in leptin after MCAO. IF/MCAO mice also exhibit infarct volumes that were less than half those of AL/MCAO mice. We observed a 30% increase in basal cell proliferation in the hippocampus and subventricular zone (SVZ) in IF/SHAM, relative to AL/SHAM mice. However, cell proliferation after MCAO was limited in IF mice, which showed twofold increases in cell proliferation relative to IF/SHAM, whereas AL/MCAO mice exhibit fivefold increases relative to AL/SHAM. Attenuation of stroke-induced neurogenesis was correlated with reductions in cell death, with AL/MCAO mice exhibiting twice the number of dying cells relative to IF/MCAO mice. These observations indicate that IF protects against neurological damage in ischemic stroke, with circulating leptin as one possible mediator.

  3. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

    Science.gov (United States)

    Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-12-15

    TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

  4. Neurotoxic effect of 2,5-hexanedione on neural progenitor cells and hippocampal neurogenesis

    International Nuclear Information System (INIS)

    Kim, Min-Sun; Park, Hee Ra; Park, Mikyung; Kim, So Jung; Kwon, Mugil; Yu, Byung Pal; Chung, Hae Young; Kim, Hyung Sik; Kwack, Seung Jun; Kang, Tae Seok; Kim, Seung Hee; Lee, Jaewon

    2009-01-01

    2,5-Hexanedione (HD), a metabolite of n-hexane, causes central and peripheral neuropathy leading to motor neuron deficits. Although chronic exposure to n-hexane is known to cause gradual sensorimotor neuropathy, there are no reports on the effects of low doses of HD on neurogenesis in the central nervous system. In the current study, we explored HD toxicity in murine neural progenitor cells (NPC), primary neuronal culture and young adult mice. HD (500 nM∼50 μM) dose-dependently suppressed NPC proliferation and cell viability, and also increased the production of reactive oxygen species (ROS). HD (10 or 50 mg/kg for 2 weeks) inhibited hippocampal neuronal and NPC proliferation in 6-week-old male ICR mice, as measured by BrdU incorporation in the dentate gyrus, indicating HD impaired hippocampal neurogenesis. In addition, elevated microglial activation was observed in the hippocampal CA3 region and lateral ventricles of HD-treated mice. Lastly, HD dose-dependently decreased the viability of primary cultured neurons. Based on biochemical and histochemical evidence from both cell culture and HD-treated animals, the neurotoxic mechanisms by which HD inhibits NPC proliferation and hippocampal neurogenesis may relate to its ability to elicit an increased generation of deleterious ROS.

  5. Long-term cognitive deficits accompanied by reduced neurogenesis after soman poisoning

    NARCIS (Netherlands)

    Joosen, M.J.A.; Jousma, E.; van den Boom, T.M.; Kuijpers, W.C.; Smit, A.B.; Lucassen, P.J.; van Helden, H.P.M.

    2009-01-01

    To date, treatment of organophosphate (OP) poisoning shows several shortcomings, and OP-victims might suffer from lasting cognitive deficits and sleep-wake disturbances. In the present study, long-term effects of soman poisoning on learning ability, memory and neurogenesis were investigated in rats,

  6. Changes in fine structure of pericytes and novel desmin-immunopositive perivascular cells during postnatal development in rat anterior pituitary gland.

    Science.gov (United States)

    Jindatip, Depicha; Fujiwara, Ken; Horiguchi, Kotaro; Tsukada, Takehiro; Kouki, Tom; Yashiro, Takashi

    2013-09-01

    Pericytes are perivascular cells associated with capillaries. We previously demonstrated that pericytes, identified by desmin immunohistochemistry, produce type I and III collagens in the anterior pituitary gland of adult rats. In addition, we recently used desmin immunoelectron microscopy to characterize a novel type of perivascular cell, dubbed a desmin-immunopositive perivascular cell, in the anterior pituitary. These two types of perivascular cells differ in fine structure. The present study attempted to characterize the morphological features of pituitary pericytes and novel desmin-immunopositive perivascular cells during postnatal development, in particular their role in collagen synthesis. Desmin immunostaining revealed numerous perivascular cells at postnatal day 5 (P5) and P10. Transmission electron microscopy showed differences in the fine structure of the two cell types, starting at P5. Pericytes had well-developed rough endoplasmic reticulum and Golgi apparatus at P5 and P10. The novel desmin-immunopositive perivascular cells exhibited dilated cisternae of rough endoplasmic reticulum at P5-P30. In addition, during early postnatal development in the gland, a number of type I and III collagen-expressing cells were observed, as were high expression levels of these collagen mRNAs. We conclude that pituitary pericytes and novel desmin-immunopositive perivascular cells contain well-developed cell organelles and that they actively synthesize collagens during the early postnatal period.

  7. Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis

    Science.gov (United States)

    Opendak, Maya; Offit, Lily; Monari, Patrick; Schoenfeld, Timothy J.; Sonti, Anup N.; Cameron, Heather A.

    2016-01-01

    Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Social disruption produced a preference for familiar over novel conspecifics, a change that did not involve global memory impairments or increased anxiety. Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels. Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP–thymidine kinase rats resulted in social behavior similar to disrupted rats. Together, these results provide novel mechanistic evidence that social disruption shapes behavior in a potentially adaptive way, possibly by reducing adult neurogenesis in the hippocampus. SIGNIFICANCE STATEMENT To investigate cellular processes underlying adaptation to social instability, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Unexpectedly, these changes were accompanied by changes in social strategies without evidence of impairments in cognition or anxiety regulation. Restoring adult neurogenesis in disrupted rats using oxytocin and conditionally suppressing the production of new neurons in socially naive GFAP–thymidine kinase rats showed that loss of 6-week-old neurons may be responsible for adaptive changes in social behavior. PMID:27358459

  8. Early Life Stages

    Science.gov (United States)

    Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

  9. Postnatal TLR2 activation impairs learning and memory in adulthood.

    Science.gov (United States)

    Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

    2015-08-01

    Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Nootropic agents stimulate neurogenesis. Brain Cells, Inc.: WO2007104035.

    Science.gov (United States)

    Taupin, Philippe

    2009-05-01

    The application is in the field of adult neurogenesis, neural stem cells and cellular therapy. It aims to characterize the activity of nootropic agents on adult neurogenesis in vitro. Nootropic agents are substances improving cognitive and mental abilities. AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and nootropic agents were assessed for the potential to differentiate human neural progenitor and stem cells into neuronal cells in vitro. They were also tested for their behavioural activity on the novel object recognition task. AMPA, piracetam, FK-960 and SGS-111 induce and stimulate neuronal differentiation of human-derived neural progenitor and stem cells. SGS-111 increases the number of visits to the novel object. The neurogenic activity of piracetam and SGS-111 is mediated through AMPA receptor. The neurogenic activity of SGS-111 may contribute and play a role in its nootropic activity. These results suggest that nootropic agents may elicit some of their effects through their neurogenic activity. The application claims the use of nootropic agents for their neurogenic activity and for the treatment of neurological diseases, disorders and injuries, by stimulating or increasing the generation of neuronal cells in the adult brain.

  11. Environmental change during postnatal development alters behaviour, cognitions and neurogenesis of mice.

    Science.gov (United States)

    Iso, Hiroyuki; Simoda, Shigero; Matsuyama, Tomohiro

    2007-04-16

    Four groups of male C57BL/6 mice were reared differing combinations of the two environments from 3 to 11 weeks after birth. At 12 and 13 weeks they were assessed by measures of behaviour and learning: open-field activity, auditory startle reflex and prepulse inhibition, water maze learning, and passive avoidance. Another four groups of mice reared under these varying conditions were examined for generation of neurons in hippocampus and cerebral cortex using bromodeoxyuridine (BrdU) at 12 weeks. Enriched (EE) and impoverished (PP) groups were housed in their respective environment for 8 weeks, enriched-impoverished (EP) and impoverished-enriched (PE) mice respectively were reared for 6 weeks in the first-mentioned environment and then for 2 weeks in the second. PP and EP mice showed hyperactivity, greater startle amplitude and significantly slower learning in a water maze than EE or PE animals, and also showed a memory deficit in a probe test, avoidance performance did not differ. Neural generation was greater in the EE and PE than PP and EP groups, especially in the hippocampus. These results suggest that environmental change critically affects behavioural and anatomic brain development, even if brief. In these mice, the effect of unfavourable early experience could be reversed by a later short of favourable experience.

  12. HIV/AIDS and Postnatal Depression at the University Teaching ...

    African Journals Online (AJOL)

    Objective: To study the contribution of HIV/AIDS to the problem of postnatal depression among women receiving postnatal care at University Teaching Hospital (UTH), Lusaka, Zambia. Background: Postnatal depression (PND), a major depressive episode during the puerperium, affects between 10% and 22% of adult ...

  13. Unlocking mechanisms in interleukin-1β-induced changes in hippocampal neurogenesis--a role for GSK-3β and TLX.

    Science.gov (United States)

    Green, H F; Nolan, Y M

    2012-11-20

    Glycogen synthase kinase-3β (GSK-3β) and the orphan nuclear receptor tailless homolog (TLX) are key regulators of hippocampal neurogenesis, which has been reported to be dysregulated in both neurodegenerative and psychiatric disorders. Inflammation is also implicated in the neuropathology of these disorders because of increased levels of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the brain. At elevated levels, IL-1β signaling through the IL-1 receptor type 1 has been shown to be detrimental to hippocampal neurogenesis. TLX is required to maintain neural stem/progenitor cells (NSPCs) in an undifferentiated state and is involved in NSPC fate determination, while GSK-3β negatively regulates Wnt signaling, a vital pathway promoting neurogenesis. This study shows that GSK-3β inhibition using a small-molecule inhibitor and the mood stabilizer lithium restores the IL-1β-induced decrease in NSPC proliferation and neuronal differentiation of embryonic rat hippocampal NSPCs to control levels. The IL-1β-induced effect on NSPCs is paralleled by a decrease in TLX expression that can be prevented by GSK-3β inhibition. The present results suggest that GSK-3β ameliorates the anti-proliferative and pro-gliogenic effects of IL-1β, and that TLX is vulnerable to inflammatory insult. Strategies to reduce GSK-3β activity or to increase TLX expression may facilitate the restoration of hippocampal neurogenesis in neuroinflammatory conditions where neurogenesis is impaired.

  14. Enhanced IL-1beta production in response to the activation of hippocampal glial cells impairs neurogenesis in aged mice.

    Science.gov (United States)

    Kuzumaki, Naoko; Ikegami, Daigo; Imai, Satoshi; Narita, Michiko; Tamura, Rie; Yajima, Marie; Suzuki, Atsuo; Miyashita, Kazuhiko; Niikura, Keiichi; Takeshima, Hideyuki; Ando, Takayuki; Ushijima, Toshikazu; Suzuki, Tsutomu; Narita, Minoru

    2010-09-01

    A variety of mechanisms that contribute to the accumulation of age-related damage and the resulting brain dysfunction have been identified. Recently, decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. However, the molecular mechanism of decreased neurogenesis with aging is still unclear. In the present study, we investigated whether aging decreases neurogenesis accompanied by the activation of microglia and astrocytes, which increases the expression of IL-1beta in the hippocampus, and whether in vitro treatment with IL-1beta in neural stem cells directly impairs neurogenesis. Ionized calcium-binding adaptor molecule 1 (Iba1)-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes were increased in the dentate gyrus of the hippocampus of 28-month-old mice. Furthermore, the mRNA level of IL-1beta was significantly increased without related histone modifications. Moreover, a significant increase in lysine 9 on histone H3 (H3K9) trimethylation at the promoter of NeuroD (a neural progenitor cell marker) was observed in the hippocampus of aged mice. In vitro treatment with IL-1beta in neural stem cells prepared from whole brain of E14.5 mice significantly increased H3K9 trimethylation at the NeuroD promoter. These findings suggest that aging may decrease hippocampal neurogenesis via epigenetic modifications accompanied by the activation of microglia and astrocytes with the increased expression of IL-1beta in the hippocampus.

  15. Developmental post-natal stress can alter the effects of pre-natal stress on the adult redox balance.

    Science.gov (United States)

    Marasco, Valeria; Spencer, Karen A; Robinson, Jane; Herzyk, Pawel; Costantini, David

    2013-09-15

    Across diverse vertebrate taxa, stressful environmental conditions during development can shape phenotypic trajectories of developing individuals, which, while adaptive in the short-term, may impair health and survival in adulthood. Regardless, the long-lasting benefits or costs of early life stress are likely to depend on the conditions experienced across differing stages of development. Here, we used the Japanese quail (Coturnix coturnix japonica) to experimentally manipulate exposure to stress hormones in developing individuals. We tested the hypothesis that interactions occurring between pre- and post-natal developmental periods can induce long-term shifts on the adult oxidant phenotype in non-breeding sexually mature individuals. We showed that early life stress can induce long-term alterations in the basal antioxidant defences. The magnitude of these effects depended upon the timing of glucocorticoid exposure and upon interactions between the pre- and post-natal stressful stimuli. We also found differences among tissues with stronger effects in the erythrocytes than in the brain in which the long-term effects of glucocorticoids on antioxidant biomarkers appeared to be region-specific. Recent experimental work has demonstrated that early life exposure to stress hormones can markedly reduce adult survival (Monaghan et al., 2012). Our results suggest that long-term shifts in basal antioxidant defences might be one of the potential mechanisms driving such accelerated ageing processes and that post-natal interventions during development may be a potential tool to shape the effects induced by pre-natally glucococorticoid-exposed phenotypes. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Pre- and postnatal exposure to low dose glufosinate ammonium induces autism-like phenotypes in mice.

    Science.gov (United States)

    Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hébert, Betty; Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Mazaud-Guittot, Séverine; Lesné, Laurianne; Briault, Sylvain; Jegou, Bernard; Pichon, Jacques; Montécot-Dubourg, Céline; Mortaud, Stéphane

    2014-01-01

    Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits - was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.

  17. Magnetic resonance beacon to detect intracellular microRNA during neurogenesis.

    Science.gov (United States)

    Lee, Jonghwan; Jin, Yeon A; Ko, Hae Young; Lee, Yong Seung; Heo, Hyejung; Cho, Sujeong; Kim, Soonhag

    2015-02-01

    Magnetic resonance imaging (MRI) offers great spatial resolution for viewing deep tissues and anatomy. We developed a self-assembling signal-on magnetic fluorescence nanoparticle to visualize intracellular microRNAs (miRNAs or miRs) during neurogenesis using MRI. The self-assembling nanoparticle (miR124a MR beacon) was aggregated by the incubation of three different oligonucleotides: a 3' adaptor, a 5' adaptor, and a linker containing miR124a-binding sequences. The T2-weighted magnetic resonance (MR) signal of the self-assembled nanoparticle was quenched when miR124a was absent from test tubes or was minimally expressed in cells and tissues. When miR124a was present in test tubes or highly expressed in vitro and in vivo during P19 cell neurogenesis, it hybridized with the miR124a MR beacon, causing the linker to detach, resulting in increased signal-on MRI intensity. This MR beacon can be used as a new imaging probe to monitor the miRNA-mediated regulation of cellular processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Effects of prenatal and postnatal parent depressive symptoms on adopted child HPA regulation: independent and moderated influences.

    Science.gov (United States)

    Laurent, Heidemarie K; Leve, Leslie D; Neiderhiser, Jenae M; Natsuaki, Misaki N; Shaw, Daniel S; Harold, Gordon T; Reiss, David

    2013-05-01

    This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck Depression Inventory in a sample of 192 families as part of the Early Growth and Development adoption Study. Child morning/evening cortisol levels and child symptoms of internalizing disorders (according to mother/father report on the Child Behavior Checklist) were assessed at 54 months, and birth mother diurnal cortisol was measured at 48 months postnatal. Hierarchical linear modeling was used to test main effects and interactions of parents' symptoms predicting child cortisol, controlling for birth mother cortisol. Prenatal exposure to birth mother symptoms predicted lower child cortisol (main effect), as did postnatal exposure to adoptive parent symptoms (interaction effects). Adoptive mother 9-month symptoms exacerbated cortisol-lowering effects of both concurrent paternal symptoms and later (27-month) maternal symptoms, and the effect of birth mother cortisol. Lower child cortisol, in turn, was associated with higher child internalizing symptoms. Implications are discussed with respect to the intergenerational transmission of depression risk.

  19. S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Indira Mendez-David

    2017-07-01

    Full Text Available Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor’s (AMPAR activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S 47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT and in the Chronic Mild Stress (CMS model in rats. Four doses of S 47445 (0.3 to 10 mg/kg, oral route, 4 and 5 weeks, respectively were assessed in both models. In mouse, behavioral effects were tested in various anxiety-and depression-related behaviors : the elevated plus maze (EPM, open field (OF, splash test (ST, forced swim test (FST, tail suspension test (TST, fur coat state and novelty suppressed feeding (NSF as well as on hippocampal neurogenesis and dendritic arborization in comparison to chronic fluoxetine treatment (18 mg/kg, p.o.. In rats, behavioral effects of S 47445 were monitored using sucrose consumption and compared to those of imipramine or venlafaxine (10 mg/kg, i.p. during the whole treatment period and after withdrawal of treatments. In a mouse model of genetic ablation of hippocampal neurogenesis (GFAP-Tk model, neurogenesis dependent/independent effects of chronic S 47445 treatment were tested, as well as BDNF hippocampal expression. S 47445 reversed CORT-induced depressive-like state by increasing grooming duration and reversing coat state’s deterioration. S 47445 also decreased the immobility duration in TST and FST. The highest doses (3 and 10 mg/kg seem the most effective for antidepressant-like activity in CORT mice. Furthermore, S 47445 significantly reversed the anxiety phenotype observed in OF (at 1 mg/kg and EPM (from 1 mg/kg. In the CMS

  20. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

    Science.gov (United States)

    Albertoni Borghese, María F; Ortiz, María C; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P

    2016-01-01

    Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

  1. Reaching mothers and babies with early postnatal home visits: the implementation realities of achieving high coverage in large-scale programs.

    Directory of Open Access Journals (Sweden)

    Deborah Sitrin

    Full Text Available BACKGROUND: Nearly half of births in low-income countries occur without a skilled attendant, and even fewer mothers and babies have postnatal contact with providers who can deliver preventive or curative services that save lives. Community-based maternal and newborn care programs with postnatal home visits have been tested in Bangladesh, Malawi, and Nepal. This paper examines coverage and content of home visits in pilot areas and factors associated with receipt of postnatal visits. METHODS: Using data from cross-sectional surveys of women with live births (Bangladesh 398, Malawi: 900, Nepal: 615, generalized linear models were used to assess the strength of association between three factors - receipt of home visits during pregnancy, birth place, birth notification - and receipt of home visits within three days after birth. Meta-analytic techniques were used to generate pooled relative risks for each factor adjusting for other independent variables, maternal age, and education. FINDINGS: The proportion of mothers and newborns receiving home visits within three days after birth was 57% in Bangladesh, 11% in Malawi, and 50% in Nepal. Mothers and newborns were more likely to receive a postnatal home visit within three days if the mother received at least one home visit during pregnancy (OR2.18, CI1.46-3.25, the birth occurred outside a facility (OR1.48, CI1.28-1.73, and the mother reported a CHW was notified of the birth (OR2.66, CI1.40-5.08. Checking the cord was the most frequently reported action; most mothers reported at least one action for newborns. CONCLUSIONS: Reaching mothers and babies with home visits during pregnancy and within three days after birth is achievable using existing community health systems if workers are available; linked to communities; and receive training, supplies, and supervision. In all settings, programs must evaluate what community delivery systems can handle and how to best utilize them to improve postnatal care

  2. Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly.

    Directory of Open Access Journals (Sweden)

    Hanqian Mao

    2016-09-01

    Full Text Available The exon junction complex (EJC is an RNA binding complex comprised of the core components Magoh, Rbm8a, and Eif4a3. Human mutations in EJC components cause neurodevelopmental pathologies. Further, mice heterozygous for either Magoh or Rbm8a exhibit aberrant neurogenesis and microcephaly. Yet despite the requirement of these genes for neurodevelopment, the pathogenic mechanisms linking EJC dysfunction to microcephaly remain poorly understood. Here we employ mouse genetics, transcriptomic and proteomic analyses to demonstrate that haploinsufficiency for each of the 3 core EJC components causes microcephaly via converging regulation of p53 signaling. Using a new conditional allele, we first show that Eif4a3 haploinsufficiency phenocopies aberrant neurogenesis and microcephaly of Magoh and Rbm8a mutant mice. Transcriptomic and proteomic analyses of embryonic brains at the onset of neurogenesis identifies common pathways altered in each of the 3 EJC mutants, including ribosome, proteasome, and p53 signaling components. We further demonstrate all 3 mutants exhibit defective splicing of RNA regulatory proteins, implying an EJC dependent RNA regulatory network that fine-tunes gene expression. Finally, we show that genetic ablation of one downstream pathway, p53, significantly rescues microcephaly of all 3 EJC mutants. This implicates p53 activation as a major node of neurodevelopmental pathogenesis following EJC impairment. Altogether our study reveals new mechanisms to help explain how EJC mutations influence neurogenesis and underlie neurodevelopmental disease.

  3. TLX: A master regulator for neural stem cell maintenance and neurogenesis.

    Science.gov (United States)

    Islam, Mohammed M; Zhang, Chun-Li

    2015-02-01

    The orphan nuclear receptor TLX, also known as NR2E1, is an essential regulator of neural stem cell (NSC) self-renewal, maintenance, and neurogenesis. In vertebrates, TLX is specifically localized to the neurogenic regions of the forebrain and retina throughout development and adulthood. TLX regulates the expression of genes involved in multiple pathways, such as the cell cycle, DNA replication, and cell adhesion. These roles are primarily performed through the transcriptional repression or activation of downstream target genes. Emerging evidence suggests that the misregulation of TLX might play a role in the onset and progression of human neurological disorders making this factor an ideal therapeutic target. Here, we review the current understanding of TLX function, expression, regulation, and activity significant to NSC maintenance, adult neurogenesis, and brain plasticity. This article is part of a Special Issue entitled: Nuclear receptors in animal development. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Postnatal nutrition influences male attractiveness and promotes plasticity in male mating preferences

    OpenAIRE

    Noguera, José C; Metcalfe, Neil B.; Monaghan, Pat

    2017-01-01

    Poor early-life nutrition could reduce adult reproductive success by negatively affecting traits linked to sexual attractiveness such as song complexity. If so, this might favor strategic mate choice, allowing males with less complex songs to tailor their mating tactics to maximize the reproductive benefits. However, this possibility has been ignored in theoretical and empirical studies. By manipulating the micronutrient content of the diet (e.g., low or high) during the postnatal period of m...

  5. Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

    Science.gov (United States)

    Goodfellow, Molly J; Lindquist, Derick H

    2014-09-01

    In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock. © 2014 Wiley Periodicals, Inc.

  6. Microglia and their CX3CR1 signaling are involved in hippocampal- but not olfactory bulb-related memory and neurogenesis.

    Science.gov (United States)

    Reshef, Ronen; Kreisel, Tirzah; Beroukhim Kay, Dorsa; Yirmiya, Raz

    2014-10-01

    Recent studies demonstrate that microglia play an important role in cognitive and neuroplasticity processes, at least partly via microglial CX3C receptor 1 (CX3CR1) signaling. Furthermore, microglia are responsive to environmental enrichment (EE), which modulates learning, memory and neurogenesis. In the present study we examined the role of microglial CX3CR1 signaling in hippocampal- and olfactory-bulb (OB)-related memory and neurogenesis in homozygous mice with microglia-specific transgenic expression of GFP under the CX3CR1 promoter (CX3CR1(-/-) mice), in which the CX3CR1 gene is functionally deleted, as well as heterozygous CX3CR1(+/-) and WT controls. We report that the CX3CR1-deficient mice displayed better hippocampal-dependent memory functioning and olfactory recognition, along with increased number and soma size of hippocampal microglia, suggestive of mild activation status, but no changes in OB microglia. A similar increase in hippocampal-dependent memory functioning and microglia number was also induced by pharmacological inhibition of CX3CR1 signaling, using chronic (2weeks) i.c.v. administration of CX3CR1 blocking antibody. In control mice, EE improved hippocampal-dependent memory and neurogenesis, and increased hippocampal microglia number and soma size, whereas odor enrichment (OE) improved olfactory recognition and OB neurogenesis without changing OB microglia status. In CX3CR1-deficient mice, EE and OE did not produce any further improvement in memory functioning or neurogenesis and had no effect on microglial status. These results support the notion that in the hippocampus microglia and their interactions with neurons via the CX3CR1 play an important role in memory functioning and neurogenesis, whereas in the OB microglia do not seem to be involved in these processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Determinants of postnatal care non-utilization among women in Nigeria.

    Science.gov (United States)

    Somefun, Oluwaseyi Dolapo; Ibisomi, Latifat

    2016-01-11

    Although, there are several programs in place in Nigeria to ensure maternal and child health, maternal and neonatal mortality rates remain high with maternal mortality rates being 576/100,000 and neonatal mortality rates at 37/1000 live births (NDHS, 2013). While there are many studies on the utilization of maternal health services such as antenatal care and skilled delivery at birth, studies on postnatal care are limited. Therefore, the aim of this study is to examine the factors associated with the non-utilization of postnatal care among mothers in Nigeria using the Nigeria Demographic and Health Survey (NDHS) 2013. For analysis, the postnatal care uptake for 19,418 children born in the 5 years preceding the survey was considered. The dependent variable was a composite variable derived from a list of questions on postnatal care. A multinomial logistic regression model was applied to examine the adjusted and unadjusted determinants of non-utilization of postnatal care. Results from this study showed that 63% of the mothers of the 19,418 children did not utilize postnatal care services in the period examined. About 42% of the study population between 25 and 34 years did not utilize postnatal care and 61% of the women who did not utilize postnatal care had no education. Results from multinomial logistic regression show that antenatal care use, distance, education, place of delivery, region and wealth status are significantly associated with the non-utilization of postnatal care services. This study revealed the low uptake of postnatal care service in Nigeria. To increase mothers' utilization of postnatal care services and improve maternal and child health in Nigeria, interventions should be targeted at women in remote areas who don't have access to services and developing mobile clinics. In addition, it is crucial that steps should be taken on educating women. This would have a significant influence on their perceptions about the use of postnatal care services in

  8. The interplay between the hippocampus and the amygdala in regulating aberrant hippocampal neurogenesis during protracted abstinence from alcohol dependence

    Directory of Open Access Journals (Sweden)

    Chitra D Mandyam

    2013-06-01

    Full Text Available The development of alcohol dependence involves elevated anxiety, low mood, and increased sensitivity to stress, collectively labeled negative affect. Particularly interesting is the recent accumulating evidence that sensitized extrahypothalamic stress systems (e.g., hyperglutamatergic activity, blunted hypothalamic-pituitary-adrenal [HPA] hormonal levels, altered corticotropin-releasing factor signaling, and altered glucocorticoid receptor signaling in the extended amygdala are evident in withdrawn dependent rats, supporting the hypothesis that pathological neuroadaptations in the extended amygdala contribute to the negative affective state. Notably, hippocampal neurotoxicity observed as aberrant dentate gyrus (DG neurogenesis (neurogenesis is a process where neural stem cells in the adult hippocampal subgranular zone generate DG granule cell neurons and DG neurodegeneration are observed in withdrawn dependent rats. These correlations between withdrawal and aberrant neurogenesis in dependent rats suggest that alterations in the DG could be hypothesized to be due to compromised HPA axis activity and associated hyperglutamatergic activity originating from the basolateral amygdala in withdrawn dependent rats. This review discusses a possible link between the neuroadaptations in the extended amygdala stress systems and the resulting pathological plasticity that could facilitate recruitment of new emotional memory circuits in the hippocampus as a function of aberrant DG neurogenesis.

  9. Comparative lophotrochozoan neurogenesis and larval neuroanatomy: recent advances from previously neglected taxa

    DEFF Research Database (Denmark)

    Wanninger, A

    2008-01-01

    Recently, a number of neurodevelopmental studies of hitherto neglected taxa have become available, contributing to questions relating to the evolution of the nervous system of Lophotrochozoa (Spiralia + Lophophorata). As an example, neurogenesis of echiurans showed that these worm-shaped spiralia...

  10. Crying babies, tired mothers - challenges of the postnatal hospital stay: an interpretive phenomenological study

    Directory of Open Access Journals (Sweden)

    Biedermann Johanna

    2010-05-01

    Full Text Available Abstract Background According to an old Swiss proverb, "a new mother lazing in childbed is a blessing to her family". Today mothers rarely enjoy restful days after birth, but enter directly into the challenge of combining baby- and self-care. They often face a combination of infant crying and personal tiredness. Yet, routine postnatal care often lacks effective strategies to alleviate these challenges which can adversely affect family health. We explored how new mothers experience and handle postnatal infant crying and their own tiredness in the context of changing hospital care practices in Switzerland. Methods Purposeful sampling was used to enroll 15 mothers of diverse parity and educational backgrounds, all of who had given birth to a full term healthy neonate. Using interpretive phenomenology, we analyzed interview and participant observation data collected during the postnatal hospital stay and at 6 and 12 weeks post birth. This paper reports on the postnatal hospital experience. Results Women's personal beliefs about beneficial childcare practices shaped how they cared for their newborn's and their own needs during the early postnatal period in the hospital. These beliefs ranged from an infant-centered approach focused on the infant's development of a basic sense of trust to an approach that balanced the infants' demands with the mother's personal needs. Getting adequate rest was particularly difficult for mothers striving to provide infant-centered care for an unsettled neonate. These mothers suffered from sleep deprivation and severe tiredness unless they were able to leave the baby with health professionals for several hours during the night. Conclusion New mothers often need permission to attend to their own needs, as well as practical support with childcare to recover from birth especially when neonates are fussy. To strengthen family health from the earliest stage, postnatal care should establish conditions which enable new mothers

  11. Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats

    Directory of Open Access Journals (Sweden)

    Adel Jungling

    2017-02-01

    Full Text Available Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD. The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.

  12. The dwelling space of postnatal care.

    Science.gov (United States)

    Smythe, Elizabeth A; Payne, Deborah; Wilson, Sally; Wynyard, Sue

    2013-06-01

    This paper considers the dwelling space of postnatal care, how being-there feels for the woman going through the experience of matrescence. The research takes a hermeneutic approach and draws on philosophical notions from Heidegger. 'What is the nature of the dwelling space of valued postnatal care?'. Appropriate ethics approval was gained. Participants were midwives, nurses, women, and other relevant stakeholders. There were 4 focus groups involving 11 participants and 19 individual interviews. Data collection was conducted over a one week period by a team of three researchers. An interview schedule had been organised by the administrator at the Centre. Participants chose whether to come to the centre to be interviewed, or be interviewed in their own homes. Most interviews were an hour. All interviews were tape recorded and transcribed, with the participant's permission. Data was analysed through a hermeneutic process set in the context of related literature. When women are invited into a dwelling space that strengthens them they feel 'mothered': being listened to, have their needs anticipated, and are cared for in a loving manner. In such a way they grow confidence. A child health nurse reported the difference such care made to on-going mothering at home. All women deserve a dwelling space in their early days of matrescence. Small birthing centres perhaps achieve such care and ambience more easily than large institutional units. Nevertheless, wherever the place, practices need to be enabled that foster the spirit of dwelling. Copyright © 2012 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  13. Adult neurogenesis affects motivation to obtain weak, but not strong, reward in operant tasks.

    Science.gov (United States)

    Karlsson, Rose-Marie; Wang, Alice S; Sonti, Anup N; Cameron, Heather A

    2018-04-16

    Decreased motivation to seek rewards is a key feature of mood disorders that correlates with severity and treatment outcome. This anhedonia, or apathy, likely reflects impairment in reward circuitry, but the specific neuronal populations controlling motivation are unclear. Granule neurons generated in the adult hippocampus have been implicated in mood disorders, but are not generally considered as part of reward circuits. We investigated a possible role of these new neurons in motivation to work for food and sucrose rewards in operant conditioning tasks using GFAP-TK pharmacogenetic ablation of adult neurogenesis in both rats and mice. Rats and mice lacking adult neurogenesis showed normal lever press responding during fixed ratio training, reward devaluation, and Pavlovian Instrumental Transfer, suggesting no impairment in learning. However, on an exponentially progressive ratio schedule, or when regular chow was freely available in the testing chamber, TK rats and mice showed less effort to gain sucrose tablets. When working for balanced food tablets, which rats and mice of both genotypes strongly preferred over sucrose, the genotype effects on behavior were lost. This decrease in effort under conditions of low reward suggests that loss of adult neurogenesis decreases motivation to seek reward in a manner that may model behavioral apathy. © 2018 Wiley Periodicals, Inc.

  14. Regulation of hippocampal neurogenesis by systemic factors including stress, glucocorticoids, sleep, and inflammation

    NARCIS (Netherlands)

    Lucassen, P.J.; Oomen, C.; van Dam, A.-M.; Czéh, B.; Gage, F.H.; Kempermann, G.; Song, H.

    2008-01-01

    This review summarizes and discusses the regulation of adult neurogenesis and hippocampal cellular plasticity by systemic factors. We focus on the role of stress, glucocorticoids, and related factors such as sleep deprivation and inflammation.

  15. Memory-enhancing effects of Cuscuta japonica Choisy via enhancement of adult hippocampal neurogenesis in mice.

    Science.gov (United States)

    Moon, Minho; Jeong, Hyun Uk; Choi, Jin Gyu; Jeon, Seong Gak; Song, Eun Ji; Hong, Seon-Pyo; Oh, Myung Sook

    2016-09-15

    It is generally accepted that functional and structural changes within the hippocampus are involved in learning and memory and that adult neurogenesis in this region may modulate cognition. The extract of Cuscuta japonica Choisy (CJ) is a well-known traditional Chinese herbal medicine that has been used since ancient times as a rejuvenation remedy. The systemic effects of this herb are widely known and can be applied for the treatment of a number of physiological diseases, but there is a lack of evidence describing its effects on brain function. Thus, the present study investigated whether CJ would enhance memory function and/or increase hippocampal neurogenesis using mice orally administered with CJ water extract or vehicle for 21days. Performance on the novel object recognition and passive avoidance tests revealed that treatment with CJ dose-dependently improved the cognitive function of mice. Additionally, CJ increased the Ki-67-positive proliferating cells and the number of doublecortin-stained neuroblasts in the dentate gyrus (DG) of the hippocampus, and double labeling with 5-bromo-2-deoxyuridine and neuronal specific nuclear protein showed that CJ increased the number of mature neurons in the DG. Finally, CJ resulted in the upregulated expression of neurogenic differentiation factor, which is essential for the maturation and differentiation of granule cells in the hippocampus. Taken together, the present findings indicate that CJ stimulated neuronal cell proliferation, differentiation, and maturation, which are all processes associated with neurogenesis. Additionally, these findings suggest that CJ may improve learning and memory via the enhancement of adult hippocampal neurogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The impact of cocaine on adult hippocampal neurogenesis: Potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder.

    Science.gov (United States)

    Castilla-Ortega, Estela; Ladrón de Guevara-Miranda, David; Serrano, Antonia; Pavón, Francisco J; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2017-10-01

    After discovering that addictive drugs alter adult neurogenesis, the potential role of adult-born hippocampal neurons in drug addiction has become a promising research field, in which cocaine is the most frequently investigated drug. Although a substantial amount of pre-clinical evidence has accumulated, additional studies are required to reveal the mechanisms by which cocaine modulates adult hippocampal neurogenesis (AHN) and determine whether these adult-born neurons have a role in cocaine-related behaviors, such as cocaine-mediated cognitive symptoms. First, this review will summarize the cocaine-induced alterations in a number of neurobiological factors (neurotransmitters, neurotrophins, glucocorticoids, inflammatory mediators) that likely regulate both hippocampal-dependent learning and adult hippocampal neurogenesis after cocaine exposure. A separate section will provide a detailed review of the available literature that challenges the common view that cocaine reduces adult hippocampal neurogenesis. In fact, cocaine has a short-term anti-proliferative role, but the young adult-born neurons are apparently spared, or even enhanced, following certain cocaine protocols. Thus, we will try to reconcile this evidence with the hippocampal-dependent cognitive symptoms that are typically observed in cocaine addicts, and we will propose new directions for future studies to test the relevant hypothesis. Based on the evidence presented here, the regulation of adult hippocampal neurogenesis might be one of the many mechanisms by which cocaine sculpts hippocampus-dependent learning. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Neurogenesis in an early protostome relative: progenitor cells in the ventral nerve center of chaetognath hatchlings are arranged in a highly organized geometrical pattern.

    Science.gov (United States)

    Perez, Yvan; Rieger, Verena; Martin, Elise; Müller, Carsten H G; Harzsch, Steffen

    2013-05-01

    Emerging evidence suggests that Chaetognatha represent an evolutionary lineage that is the sister group to all other Protostomia thus promoting these animals as a pivotal model for our understanding of bilaterian evolutionary history. We have analyzed the proliferation of neuronal progenitor cells in the developing ventral nerve center (VNC) of Spadella cephaloptera hatchlings. To that end, for the first time in Chaetognatha, we performed in vivo incorporation experiments with the S-phase specific mitosis marker bromodeoxyuridine (BrdU). Our experiments provide evidence for a high level of mitotic activity in the VNC for ca. 3 days after hatching. Neurogenesis is carried by presumptive neuronal progenitor cells that cycle rapidly and most likely divide asymmetrically. These progenitors are arranged in a distinct grid-like geometrical pattern including about 35 transverse rows. Considering Chaetognaths to be an early offshoot of the protostome lineage we conclude that the presence of neuronal progenitor cells with asymmetric division seems to be a feature that is rooted deeply in the Metazoa. In the light of previous evidence indicating the presence of serially iterated peptidergic neurons with individual identities in the chaetognath VNC, we discuss if these neuronal progenitor cells give rise to distinct lineages. Furthermore, we evaluate the serially iterated arrangement of the progenitor cells in the light of evolution of segmentation. Copyright © 2013 Wiley Periodicals, Inc.

  18. Prolonged Running, not Fluoxetine Treatment, Increases Neurogenesis, but does not Alter Neuropathology, in the 3xTg Mouse Model of Alzheimer's Disease.

    NARCIS (Netherlands)

    Marlatt, M.W.; Potter, M.C.; Bayer, T.A.; van Praag, H.; Lucassen, P.J.

    2013-01-01

    Reductions in adult neurogenesis have been documented in the original 3xTg mouse model of Alzheimer's disease (AD), notably occurring at the same age when spatial memory deficits and amyloid plaque pathology appeared. As this suggested reduced neurogenesis was associated with behavioral deficits, we

  19. Olfactory memory is enhanced in mice exposed to extremely low-frequency electromagnetic fields via Wnt/β-catenin dependent modulation of subventricular zone neurogenesis.

    Science.gov (United States)

    Mastrodonato, Alessia; Barbati, Saviana Antonella; Leone, Lucia; Colussi, Claudia; Gironi, Katia; Rinaudo, Marco; Piacentini, Roberto; Denny, Christine A; Grassi, Claudio

    2018-01-10

    Exposure to extremely low-frequency electromagnetic fields (ELFEF) influences the expression of key target genes controlling adult neurogenesis and modulates hippocampus-dependent memory. Here, we assayed whether ELFEF stimulation affects olfactory memory by modulating neurogenesis in the subventricular zone (SVZ) of the lateral ventricle, and investigated the underlying molecular mechanisms. We found that 30 days after the completion of an ELFEF stimulation protocol (1 mT; 50 Hz; 3.5 h/day for 12 days), mice showed enhanced olfactory memory and increased SVZ neurogenesis. These effects were associated with upregulated expression of mRNAs encoding for key regulators of adult neurogenesis and were mainly dependent on the activation of the Wnt pathway. Indeed, ELFEF stimulation increased Wnt3 mRNA expression and nuclear localization of its downstream target β-catenin. Conversely, inhibition of Wnt3 by Dkk-1 prevented ELFEF-induced upregulation of neurogenic genes and abolished ELFEF's effects on olfactory memory. Collectively, our findings suggest that ELFEF stimulation increases olfactory memory via enhanced Wnt/β-catenin signaling in the SVZ and point to ELFEF as a promising tool for enhancing SVZ neurogenesis and olfactory function.

  20. Determining the effects of early gestation in utero heat stress on postnatal fasting heat production and circulating biomarkers associated with metabolism in growing pigs

    Science.gov (United States)

    The study objective was to determine the effects of in utero heat stress (IUHS) on postnatal fasting heat production (FHP) in growing pigs. Based on our previous observation of increased postnatal core body temperature ‘set-point’ in IUHS pigs, we hypothesized that FHP would be greater during postna...

  1. Metabolic trajectories based on 1H NMR spectra of urines from sheep exposed to nutritional challenges during prenatal and early postnatal life

    DEFF Research Database (Denmark)

    Nyberg, Nils; Nielsen, Mette Benedicte Olaf; Jaroszewski, Jerzy W.

    2010-01-01

    1H NMR metabolic profiles of urine from sheep exposed to prenatal nutritional restriction (n = 19) and a control group with normal prenatal nutritional requirements (n = 19), followed by either conventional (n = 10 + 10) or high carbohydrate high fat postnatal diet (n = 9 + 9), were studied. Urine...... undernutrition followed by normal postnatal diet showed metabolic patters that are ahead in time on the metabolic trajectory relative to the prenatal control group. No long-term effects of fetal undernutrition, alone or in combination with postnatal hypernutrition were observed....... amount of glucose, indicative of monogastric-like metabolism, and exhibiting concomitant increase of metabolites related to rumen microflora (mainly glycine conjugates of benzoic and phenylacetic acid) as the ruminal metabolism developed. Urines from young (2-month-old) animals exposed to prenatal...

  2. Mild prenatal protein malnutrition increases alpha 2C-adrenoceptor expression in the rat cerebral cortex during postnatal life.

    Science.gov (United States)

    Sierralta, Walter; Hernández, Alejandro; Valladares, Luis; Pérez, Hernán; Mondaca, Mauricio; Soto-Moyano, Rubén

    2006-05-15

    Mild reduction in the protein content in the diet of pregnant rats from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but results in significant changes of the concentration and release of cortical noradrenaline during postnatal life, together with impaired long-term potentiation and memory formation. Since some central noradrenergic receptors are critically involved in neuroplasticity, the present study evaluated, by utilizing immunohistochemical methods, the effect of mild prenatal protein malnutrition on the alpha 2C-adrenoceptor expression in the frontal and occipital cortices of 8- and 60-day-old rats. At day 8 of postnatal age, prenatally malnourished rats exhibited a three-fold increase of alpha 2C-adrenoceptor expression in both the frontal and the occipital cortices, as compared to well-nourished controls. At 60 days of age, prenatally malnourished rats showed normal expression levels scores of alpha 2C-adrenoceptor in the neocortex. Results suggest that overexpression of neocortical alpha 2C-adrenoceptors during early postnatal life, subsequent to mild prenatal protein malnutrition, could in part be responsible for neural and behavioral disturbances showing prenatally malnourished animals during the postnatal life.

  3. Antenatal risk factors for postnatal depression: a prospective study of chinese women at maternal and child health centres

    Directory of Open Access Journals (Sweden)

    Siu Bonnie WM

    2012-03-01

    Full Text Available Abstract Background Risk factors for postnatal depression (PND are under-explored in the Chinese populations. There is increasing recognition of the importance of identifying predictive factors during the antenatal period for PND. The present study aimed to identify the risk factors for postnatal depression in a community cohort of Chinese women with special focus on the antenatal risk factors. Methods Eight hundred and five Chinese women were interviewed during their third trimester of pregnancy and at around 2 months postnatally. Putative risk factors for PND were collected and the diagnosis of PND was confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders. The 2-month postnatal depression status was used as the dependent variable for univariate and multivariate analyses against putative risk factors. Results Marital dissatisfaction (Relative Risk = 8.27, dissatisfied relationship with mother-in-law (Relative Risk = 3.93, antenatal depressive symptomatology (Relative Risk = 3.90, and anxiety-prone personality (Relative Risk = 2.14 predicted PND in Chinese women independently. Conclusions Chinese women tend to keep their own feelings and emotions and it is important to monitor Chinese pregnant women with these predictive risk factors so that PND can be identified early.

  4. Postnatally acquired cytomegalovirus infections in preterm infants

    NARCIS (Netherlands)

    Nijman, J.

    2013-01-01

    A postnatal cytomegalovirus (CMV) infection is common in very low birth weight infants with an estimated prevalence of 6–59%. Breast milk from CMV seropositive mothers is the main source of postnatal CMV infection. Ninety-six percent of these mothers shed CMV in their breast milk after delivery due

  5. Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

    Science.gov (United States)

    Huang, Li-Tung

    2014-01-01

    Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

  6. Do depression, stress, sleep disruption, and inflammation alter hippocampal apoptosis and neurogenesis?

    NARCIS (Netherlands)

    Lucassen, P.J.; Meerlo, P.; Naylor, A.S.; van Dam, A.M.; Dayer, A.G.; Czeh, B.; Oomen, C.A.; Pariante, C.M.

    2009-01-01

    We discuss the regulation of cellular plasticity, focusing on neurogenesis and apoptosis in the adult hippocampus, by stress, sleep, inflammation, and depression. This is the fourth of five chapters in this book that present not only clinical data but also experimental evidence from animal models

  7. p600 regulates spindle orientation in apical neural progenitors and contributes to neurogenesis in the developing neocortex

    Directory of Open Access Journals (Sweden)

    Camille Belzil

    2014-05-01

    Full Text Available Apical neural progenitors (aNPs drive neurogenesis by means of a program consisting of self-proliferative and neurogenic divisions. The balance between these two manners of division sustains the pool of apical progenitors into late neurogenesis, thereby ensuring their availability to populate the brain with terminal cell types. Using knockout and in utero electroporation mouse models, we report a key role for the microtubule-associated protein 600 (p600 in the regulation of spindle orientation in aNPs, a cellular event that has been associated with cell fate and neurogenesis. We find that p600 interacts directly with the neurogenic protein Ndel1 and that aNPs knockout for p600, depleted of p600 by shRNA or expressing a Ndel1-binding p600 fragment all display randomized spindle orientation. Depletion of p600 by shRNA or expression of the Ndel1-binding p600 fragment also results in a decreased number of Pax6-positive aNPs and an increased number of Tbr2-positive basal progenitors destined to become neurons. These Pax6-positive aNPs display a tilted mitotic spindle. In mice wherein p600 is ablated in progenitors, the production of neurons is significantly impaired and this defect is associated with microcephaly. We propose a working model in which p600 controls spindle orientation in aNPs and discuss its implication for neurogenesis.

  8. Postnatal Development of CB1 Receptor Expression in Rodent Somatosensory Cortex

    Science.gov (United States)

    Deshmukh, Suvarna; Onozuka, Kaori; Bender, Kevin J.; Bender, Vanessa A.; Lutz, Beat; Mackie, Ken; Feldman, Daniel E.

    2007-01-01

    Endocannabinoids are powerful modulators of synaptic transmission that act on presynaptic cannabinoid receptors. Cannabinoid receptor type 1 (CB1) is the dominant receptor in the CNS, and is present in many brain regions, including sensory cortex. To investigate the potential role of CB1 receptors in cortical development, we examined the developmental expression of CB1 in rodent primary somatosensory (barrel) cortex, using immunohistochemistry with a CB1-specific antibody. We found that before postnatal day (P) 6, CB1 receptor staining was present exclusively in the cortical white matter, and that CB1 staining appeared in the grey matter between P6 and P20 in a specific laminar pattern. CB1 staining was confined to axons, and was most prominent in cortical layers 2/3, 5a, and 6. CB1 null (−/−) mice showed altered anatomical barrel maps in layer 4, with enlarged inter-barrel septa, but normal barrel size. These results indicate that CB1 receptors are present in early postnatal development and influence development of sensory maps. PMID:17210229

  9. Post-stroke gaseous hypothermia increases vascular density but not neurogenesis in the ischemic penumbra of aged rats

    DEFF Research Database (Denmark)

    Sandu, Raluca Elena; Uzoni, Adriana; Ciobanu, Ovidiu

    2016-01-01

    of several genes involved in protein degradation, thereby leading to better preservation of infarcted tissue. Further, hypothermia increased the density of newly formed blood vessels in the peri-lesional cortex did not enhance neurogenesis in the infarcted area of aged rats. Likewise, there was improved......-PCR and immunofluorescence, we assessed infarct size, vascular density, neurogenesis and as well as the expression of genes coding for proteasomal proteins as well as in post-stroke aged Sprague-Dawley rats exposed to H2S- induced hypothermia. Results: Two days exposure to mild hypothermia diminishes the expression...

  10. NMDA and kainate receptor expression, long-term potentiation, and neurogenesis in the hippocampus of long-lived Ames dwarf mice.

    Science.gov (United States)

    Sharma, Sunita; Darland, Diane; Lei, Saobo; Rakoczy, Sharlene; Brown-Borg, Holly M

    2012-06-01

    In the current study, we investigated changes in N-methyl D-aspartate (NMDA) and kainate receptor expression, long-term potentiation (LTP), and neurogenesis in response to neurotoxic stress in long-living Ames dwarf mice. We hypothesized that Ames dwarf mice have enhanced neurogenesis that enables retention of spatial learning and memory with age and promotes neurogenesis in response to injury. Levels of the NMDA receptors (NR)1, NR2A, NR2B, and the kainate receptor (KAR)2 were increased in Ames dwarf mice, relative to wild-type littermates. Quantitative assessment of the excitatory postsynaptic potential in Schaffer collaterals in hippocampal slices from Ames dwarf mice showed an increased response in high-frequency induced LTP over time compared with wild type. Kainic acid (KA) injection was used to promote neurotoxic stress-induced neurogenesis. KA mildly increased the number of doublecortin-positive neurons in wild-type mice, but the response was significantly enhanced in the Ames dwarf mice. Collectively, these data support our hypothesis that the enhanced learning and memory associated with the Ames dwarf mouse may be due to elevated levels of NMDA and KA receptors in hippocampus and their ability to continue producing new neurons in response to neuronal damage.

  11. Consequences of prenatal radiation exposure on perinatal and postnatal development

    International Nuclear Information System (INIS)

    Konermann, G.

    1982-01-01

    Acute and long-term teratogenic effects were studied in X-irradiated mice. There is evidence of a maximum susceptibility for intrauterine irradiation damage during early organogenesis with the accumulation of several processes of organ induction. Dose response curves are compared for the irradiation days 7, 10 and 13 post conceptionem based on the incidence of skeletal defects. Exposures during advanced stages of prenatal development promote the manifestation of long-term maturation defects. Corresponding postnatal phenomena and dose-relationships are described for pre- and perinatally irradiated mice. The data include late proliferative effects on liver and brain, lipid synthesis during the premyelination in brain, cerebral tigroid formation, insulin synthesis (histochemical data) in the Islands of Langerhans cells as well as disorders in the neuronal process formation. It is demonstrated that postnatal teratogenesis manifests itself as an elongated chain of interdependent processes of retardation and stabilization, the predominance of each depending on the irradiation dose and its time of application during development. In view of the generally fluctuating character of long-term maturation defects, an extended period of observation seems to be of great practical importance. (orig.)

  12. Dynamic learning and memory, synaptic plasticity and neurogenesis: an update

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš

    2014-01-01

    Roč. 8, APR 1 (2014), s. 106 ISSN 1662-5153 R&D Projects: GA ČR(CZ) GA14-03627S Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : learning * memory * synaptic plasticity * neurogenesis Subject RIV: FH - Neurology Impact factor: 3.270, year: 2014

  13. Increased radial glia quiescence, decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon.

    Science.gov (United States)

    Edelmann, Kathrin; Glashauser, Lena; Sprungala, Susanne; Hesl, Birgit; Fritschle, Maike; Ninkovic, Jovica; Godinho, Leanne; Chapouton, Prisca

    2013-09-01

    The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia. Copyright © 2013 Wiley Periodicals, Inc.

  14. Influence of superior cervical ganglionectomy on hippocampal neurogenesis and learning and memory in adult rats

    Institute of Scientific and Technical Information of China (English)

    Yanping Ding; Baoping Shao; Shiyuan Yu; Shanting Zhao; Jianlin Wang

    2009-01-01

    BACKGROUND: Studies have shown that neurogenesis in the dentate gyrus plays an important role in learning and memory. However, studies have not determined whether the superior cervical ganglion or the sympathetic nerve system influences hippocampal neurogenesis or learning and memory in adult rats. OBJECTIVE: To observe differences in dentate gyrus neurogenesis, as well as learning and memory, in adult rats following superior cervical ganglionectomy. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Immunohistochemistry Laboratory of the School of Life Sciences in Lanzhou University from July 2006 to July 2007.MATERIALS: Doublecortin polyclonal antibody was provided by Santa Cruz Biotechnology, USA;avidin-biotin-peroxidase complex was purchased from Zhongshan Goldenbride Biotechnology, China;Morris water maze was bought from Taimeng Technology, China. METHODS: A total of 20 adult, male, Wistar rats were randomly divided into surgery and control groups, with 10 rats in each group. In the surgery group, the bilateral superior cervical ganglions were transected. In the control group, the superior cervical ganglions were only exposed, but no ganglionectomy was performed. MAIN OUTCOME MEASURES: To examine distribution, morphology, and number of newborn neurons in the dentate gyrus using doublecortin immunohistochemistry at 36 days following surgical procedures. To examine ability of learning and memory in adult rats using the Morris water maze at 30 days following surgical procedures. RESULTS: Doublecortin immunohistochemical results showed that a reduction in the number of doublecortin-positive neurons in the surgery group compared to the control group (P<0.05), while the distribution of doublecortin-positive neurons was identical in the two groups. The surgery group exhibited significantly worse performance in learning and spatial memory tasks compared to the control group (P<0.05). CONCLUSION: Superior cervical ganglionectomy

  15. Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis

    Directory of Open Access Journals (Sweden)

    Alexandre A.S.F. Raposo

    2015-03-01

    Full Text Available The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.

  16. The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats

    NARCIS (Netherlands)

    Bueters, Ruud R. G.; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P.; Schreuder, Michiel F.

    2016-01-01

    Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal

  17. Xiaochaihutang attenuates depressive/anxiety-like behaviors of social isolation-reared mice by regulating monoaminergic system, neurogenesis and BDNF expression.

    Science.gov (United States)

    Ma, Jie; Wang, Fang; Yang, Jingyu; Dong, Yingxu; Su, Guangyue; Zhang, Kuo; Pan, Xing; Ma, Ping; Zhou, Tingshuo; Wu, Chunfu

    2017-08-17

    degradation enzyme (MAO A ) expression in the hippocampus of SI-reared mice for the first time. Moreover, XCHT significantly augmented hippocampal neurogenesis and BDNF expression in hippocampus of SI-reared mice. Our results showed for the first time that XCHT improved depressive/anxiety-like behaviors of SI-reared mice by regulating the monoaminergic system, neurogenesis and neurotrophin expression. The findings indicate that XCHT may have a therapeutic application for early-life stress model of depression and in turn provide further evidence supporting XCHT a novel potential antidepressant from a distinct perspective. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  18. Experiment on radiotherapy of postnatal mastitis

    International Nuclear Information System (INIS)

    Zhut'ko, A.A.

    1978-01-01

    The results of radiotherapy of postnatal mastitis in 78 women are presented. It is shown that the radiotherapy is the method of choice. Application of radiotherapy at different stages of disease promotes either complete resolution of infiltration (1-2 irradiations) or stipulates the decrease in temperature, abatement of pains and improvement of general state (at the presence of purulent fusion of mammary tissue). X-ray therapy of postnatal mastitis has does not affect the lactational function of mammary gland

  19. Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Suzhen Dong

    Full Text Available BACKGROUND: Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. METHODOLOGY: We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. CONCLUSIONS: The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity.

  20. Curcumin Enhances Neurogenesis and Cognition in Aged Rats: Implications for Transcriptional Interactions Related to Growth and Synaptic Plasticity

    Science.gov (United States)

    Mitchell, E. Siobhan; Xiu, Jin; Tiwari, Jyoti K.; Hu, Yinghe; Cao, Xiaohua; Zhao, Zheng

    2012-01-01

    Background Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. Methodology We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. Conclusions The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity. PMID:22359574

  1. Stage-specific functions of the small Rho GTPases Cdc42 and Rac1 for adult hippocampal neurogenesis

    DEFF Research Database (Denmark)

    Vadodaria, Krishna C; Brakebusch, Cord; Suter, Ueli

    2013-01-01

    The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC......) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation......, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases...

  2. Barriers to postnatal care and exclusive breastfeeding among ...

    African Journals Online (AJOL)

    Conclusion: Poor knowledge and inaccessibility to health facilities were the main obstacles to postnatal care while the practice of exclusive breastfeeding was limited by the stress and mothers refusal. Keywords: Exclusive breastfeeding, postnatal care, southeastern Nigeria, urban women. Nigerian Medical Journal | Vol.

  3. Integrative Temporo-Spatial, Mineralogic, Spectroscopic, and Proteomic Analysis of Postnatal Enamel Development in Teeth with Limited Growth

    Directory of Open Access Journals (Sweden)

    Mirali Pandya

    2017-10-01

    Full Text Available Tooth amelogenesis is a complex process beginning with enamel organ cell differentiation and enamel matrix secretion, transitioning through changes in ameloblast polarity, cytoskeletal, and matrix organization, that affects crucial biomineralization events such as mineral nucleation, enamel crystal growth, and enamel prism organization. Here we have harvested the enamel organ including the pliable enamel matrix of postnatal first mandibular mouse molars during the first 8 days of tooth enamel development to conduct a step-wise cross-sectional analysis of the changes in the mineral and protein phase. Mineral phase diffraction pattern analysis using single-crystal, powder sample X-ray diffraction analysis indicated conversion of calcium phosphate precursors to partially fluoride substituted hydroxyapatite from postnatal day 4 (4 dpn onwards. Attenuated total reflectance spectra (ATR revealed a substantial elevation in phosphate and carbonate incorporation as well as structural reconfiguration between postnatal days 6 and 8. Nanoscale liquid chromatography coupled with tandem mass spectrometry (nanoLC-MS/MS demonstrated highest protein counts for ECM/cell surface proteins, stress/heat shock proteins, and alkaline phosphatase on postnatal day 2, high counts for ameloblast cytoskeletal proteins such as tubulin β5, tropomyosin, β-actin, and vimentin on postnatal day 4, and elevated levels of cofilin-1, calmodulin, and peptidyl-prolyl cis-trans isomerase on day 6. Western blot analysis of hydrophobic enamel proteins illustrated continuously increasing amelogenin levels from 1 dpn until 8 dpn, while enamelin peaked on days 1 and 2 dpn, and ameloblastin on days 1–5 dpn. In summary, these data document the substantial changes in the enamel matrix protein and mineral phase that take place during postnatal mouse molar amelogenesis from a systems biological perspective, including (i relatively high levels of matrix protein expression during the early

  4. Running wheel training does not change neurogenesis levels or alter working memory tasks in adult rats

    Directory of Open Access Journals (Sweden)

    Cesar A. Acevedo-Triana

    2017-05-01

    Full Text Available Background Exercise can change cellular structure and connectivity (neurogenesis or synaptogenesis, causing alterations in both behavior and working memory. The aim of this study was to evaluate the effect of exercise on working memory and hippocampal neurogenesis in adult male Wistar rats using a T-maze test. Methods An experimental design with two groups was developed: the experimental group (n = 12 was subject to a forced exercise program for five days, whereas the control group (n = 9 stayed in the home cage. Six to eight weeks after training, the rats’ working memory was evaluated in a T-maze test and four choice days were analyzed, taking into account alternation as a working memory indicator. Hippocampal neurogenesis was evaluated by means of immunohistochemistry of BrdU positive cells. Results No differences between groups were found in the behavioral variables (alternation, preference index, time of response, time of trial or feeding, or in the levels of BrdU positive cells. Discussion Results suggest that although exercise may have effects on brain structure, a construct such as working memory may require more complex changes in networks or connections to demonstrate a change at behavioral level.

  5. Postnatal mandible growth in wild and laboratory mice: Differences revealed from bone remodeling patterns and geometric morphometrics.

    Science.gov (United States)

    Martínez-Vargas, Jessica; Muñoz-Muñoz, Francesc; Martinez-Maza, Cayetana; Molinero, Amalia; Ventura, Jacint

    2017-08-01

    Comparative information on the variation in the temporospatial patterning of mandible growth in wild and laboratory mice during early postnatal ontogeny is scarce but important to understand variation among wild rodent populations. Here, we compare mandible growth between two ontogenetic series from the second to the eighth week of postnatal life, corresponding to two different groups of mice reared under the same conditions: the classical inbred strain C57BL/6J, and Mus musculus domesticus. We characterize the ontogenetic patterns of bone remodeling of the mandibles belonging to these laboratory and wild mice by analyzing bone surface, as well as examine their ontogenetic form changes and bimodular organization using geometric morphometrics. Through ontogeny, the two mouse groups display similar directions of mandible growth, according to the temporospatial distribution of bone remodeling fields. The allometric shape variation of the mandibles of these mice entails the relative enlargement of the ascending ramus. The organization of the mandible into two modules is confirmed in both groups during the last postnatal weeks. However, especially after weaning, the mandibles of wild and laboratory mice differ in the timing and localization of several remodeling fields, in addition to exhibiting different patterns of shape variation and differences in size. The stimulation of dentary bone growth derived from the harder post-weaning diet might account for some features of postnatal mandible growth common to both groups. Nonetheless, a large component of the postnatal growth of the mouse mandible appears to be driven by the inherent genetic programs, which might explain between-group differences. © 2017 Wiley Periodicals, Inc.

  6. The helix-loop-helix protein id1 controls stem cell proliferation during regenerative neurogenesis in the adult zebrafish telencephalon.

    Science.gov (United States)

    Rodriguez Viales, Rebecca; Diotel, Nicolas; Ferg, Marco; Armant, Olivier; Eich, Julia; Alunni, Alessandro; März, Martin; Bally-Cuif, Laure; Rastegar, Sepand; Strähle, Uwe

    2015-03-01

    The teleost brain has the remarkable ability to generate new neurons and to repair injuries during adult life stages. Maintaining life-long neurogenesis requires careful management of neural stem cell pools. In a genome-wide expression screen for transcription regulators, the id1 gene, encoding a negative regulator of E-proteins, was found to be upregulated in response to injury. id1 expression was mapped to quiescent type I neural stem cells in the adult telencephalic stem cell niche. Gain and loss of id1 function in vivo demonstrated that Id1 promotes stem cell quiescence. The increased id1 expression observed in neural stem cells in response to injury appeared independent of inflammatory signals, suggesting multiple antagonistic pathways in the regulation of reactive neurogenesis. Together, we propose that Id1 acts to maintain the neural stem cell pool by counteracting neurogenesis-promoting signals. © 2014 AlphaMed Press.

  7. A statewide review of postnatal care in private hospitals in Victoria, Australia

    Directory of Open Access Journals (Sweden)

    Forster Della A

    2010-05-01

    Full Text Available Abstract Background Concerns have been raised in Australia and internationally regarding the quality and effectiveness of hospital postnatal care, although Australian women receiving postnatal care in the private maternity sector rate their satisfaction with care more highly than women receiving public maternity care. In Victoria, Australia, two-thirds of women receive their maternity care in the public sector and the remainder in private health care sector. A statewide review of public hospital postnatal care in Victoria from the perspective of care providers found many barriers to care provision including the busyness of postnatal wards, inadequate staffing and priority being given to other episodes of care; however the study did not include private hospitals. The aim of this study was replicate the review in the private sector, to explore the structure and organisation of postnatal care in private hospitals and identify those aspects of care potentially impacting on women's experiences and maternal and infant care. This provides a more complete overview of the organisational structures and processes in postnatal care in all Victorian hospitals from the perspective of care providers. Methods A mixed method design was used. A structured postal survey was sent to all Victorian private hospitals (n = 19 and key informant interviews were undertaken with selected clinical midwives, maternity unit managers and obstetricians (n = 11. Survey data were analysed using descriptive statistics and interview data analysed thematically. Results Private hospital care providers report that postnatal care is provided in very busy environments, and that meeting the aims of postnatal care (breastfeeding support, education of parents and facilitating rest and recovery for women following birth was difficult in the context of increased acuity of postnatal care; prioritising of other areas over postnatal care; high midwife-to-woman ratios; and the number and

  8. Pengaruh Kekurangan Protein Pre dan Postnatal Terhadap Mineralisasi Gigi

    Directory of Open Access Journals (Sweden)

    Pinandi Sri Pudyani

    2015-11-01

    Full Text Available The accuracy of nutrition quantity during and after pregnancy is needed for supporting division, differentiation and replication of cells during growth stage. Protein is needed to obtain optimally child's body growth and development including tooth. The study was aimed to deteremine the effects of pre and postnatal protein deficiency on tooth mineralization rats model. The study was carried out on 30 Rates norvegicus rats, divided in 3 groups.The first group was fed the protein deficient diet (4% during pre and postnatal period, the second was fed the protein deficient diet (4% only postnatal and the third was fed the postnatal diet. Feeding was carried out until animales aged at 56 days. After that, animals were sacrificed and the width of right mandibular molar prevention layer was histologically analyzed to know the number of tooth mineralization. The result of the study showed significant differences (p<0.05 in width of prevention layer between standard and experimental groups. It's concluded that pre and postnatal protein deficiency were inhibits tooth mineralization.

  9. The role of genes involved in neuroplasticity and neurogenesis in the observation of a gene-environment interaction (GxE) in schizophrenia.

    Science.gov (United States)

    Le Strat, Yann; Ramoz, Nicolas; Gorwood, Philip

    2009-05-01

    Schizophrenia is a multifactorial disease characterized by a high heritability. Several candidate genes have been suggested, with the strongest evidences for genes encoding dystrobrevin binding protein 1 (DTNBP1), neuregulin 1 (NRG1), neuregulin 1 receptor (ERBB4) and disrupted in schizophrenia 1 (DISC1), as well as several neurotrophic factors. These genes are involved in neuronal plasticity and play also a role in adult neurogenesis. Therefore, the genetic basis of schizophrenia could involve different factors more or less specifically required for neuroplasticity, including the synapse maturation, potentiation and plasticity as well as neurogenesis. Following the model of Knudson in tumors, we propose a two-hit hypothesis of schizophrenia. In this model of gene-environment interaction, a variant in a gene related to neurogenesis is transmitted to the descent (first hit), and, secondarily, an environmental factor occurs during the development of the central nervous system (second hit). Both of these vulnerability and trigger factors are probably necessary to generate a deficit in neurogenesis and therefore to cause schizophrenia. The literature supporting this gene x environment hypothesis is reviewed, with emphasis on some molecular pathways, raising the possibility to propose more specific molecular medicine.

  10. The neurogenic factor NeuroD1 is expressed in post-mitotic cells during juvenile and adult Xenopus neurogenesis and not in progenitor or radial glial cells.

    Directory of Open Access Journals (Sweden)

    Laure Anne D'Amico

    Full Text Available In contrast to mammals that have limited proliferation and neurogenesis capacities, the Xenopus frog exhibit a great potential regarding proliferation and production of new cells in the adult brain. This ability makes Xenopus a useful model for understanding the molecular programs required for adult neurogenesis. Transcriptional factors that control adult neurogenesis in vertebrate species undergoing widespread neurogenesis are unknown. NeuroD1 is a member of the family of proneural genes, which function during embryonic neurogenesis as a potent neuronal differentiation factor. Here, we study in detail the expression of NeuroD1 gene in the juvenile and adult Xenopus brains by in situ hybridization combined with immunodetections for proliferation markers (PCNA, BrdU or in situ hybridizations for cell type markers (Vimentin, Sox2. We found NeuroD1 gene activity in many brain regions, including olfactory bulbs, pallial regions of cerebral hemispheres, preoptic area, habenula, hypothalamus, cerebellum and medulla oblongata. We also demonstrated by double staining NeuroD1/BrdU experiments, after long post-BrdU administration survival times, that NeuroD1 gene activity was turned on in new born neurons during post-metamorphic neurogenesis. Importantly, we provided evidence that NeuroD1-expressing cells at this brain developmental stage were post-mitotic (PCNA- cells and not radial glial (Vimentin+ or progenitors (Sox2+ cells.

  11. Predictors of intelligence at the age of 5: family, pregnancy and birth characteristics, postnatal influences, and postnatal growth.

    Science.gov (United States)

    Eriksen, Hanne-Lise Falgreen; Kesmodel, Ulrik Schiøler; Underbjerg, Mette; Kilburn, Tina Røndrup; Bertrand, Jacquelyn; Mortensen, Erik Lykke

    2013-01-01

    Parental education and maternal intelligence are well-known predictors of child IQ. However, the literature regarding other factors that may contribute to individual differences in IQ is inconclusive. The aim of this study was to examine the contribution of a number of variables whose predictive status remain unclarified, in a sample of basically healthy children with a low rate of pre- and postnatal complications. 1,782 5-year-old children sampled from the Danish National Birth Cohort (2003-2007) were assessed with a short form of the Wechsler Preschool and Primary Scale of Intelligence - Revised. Information on parental characteristics, pregnancy and birth factors, postnatal influences, and postnatal growth was collected during pregnancy and at follow-up. A model including study design variables and child's sex explained 7% of the variance in IQ, while parental education and maternal IQ increased the explained variance to 24%. Other predictors were parity, maternal BMI, birth weight, breastfeeding, and the child's head circumference and height at follow-up. These variables, however, only increased the explained variance to 29%. The results suggest that parental education and maternal IQ are major predictors of IQ and should be included routinely in studies of cognitive development. Obstetrical and postnatal factors also predict IQ, but their contribution may be of comparatively limited magnitude.

  12. Postnatal Innate Immune Development: From Birth to Adulthood

    Directory of Open Access Journals (Sweden)

    Anastasia Georgountzou

    2017-08-01

    Full Text Available It is well established that adaptive immune responses are deficient in early life, contributing to increased mortality and morbidity. The developmental trajectories of different components of innate immunity are only recently being explored. Individual molecules, cells, or pathways of innate recognition and signaling, within different compartments/anatomical sites, demonstrate variable maturation patterns. Despite some discrepancies among published data, valuable information is emerging, showing that the developmental pattern of cytokine responses during early life is age and toll-like receptor specific, and may be modified by genetic and environmental factors. Interestingly, specific environmental exposures have been linked both to innate function modifications and the occurrence of chronic inflammatory disorders, such as respiratory allergies. As these conditions are on the rise, our knowledge on innate immune development and its modulating factors needs to be expanded. Improved understanding of the sequence of events associated with disease onset and persistence will lead toward meaningful interventions. This review describes the state-of-the-art on normal postnatal innate immune ontogeny and highlights research areas that are currently explored or should be further addressed.

  13. Phospholipase D family member 4, a transmembrane glycoprotein with no phospholipase D activity, expression in spleen and early postnatal microglia.

    Directory of Open Access Journals (Sweden)

    Fumio Yoshikawa

    -PLD, HKD motif-carrying, transmembrane glycoprotein localized in the endoplasmic reticulum and Golgi apparatus. The spatiotemporally restricted expression patterns suggested that PLD4 might play a role in common function(s among microglia during early postnatal brain development and splenic marginal zone cells.

  14. CXCR4 antagonist AMD3100 reverses the neurogenesis and behavioral recovery promoted by forced limb-use in stroke rats.

    Science.gov (United States)

    Zhao, Shanshan; Qu, Huiling; Zhao, Yi; Xiao, Ting; Zhao, Mei; Li, Yong; Jolkkonen, Jukka; Cao, Yunpeng; Zhao, Chuansheng

    2015-01-01

    Forced limb-use can enhance neurogenesis and behavioral recovery as well as increasing the level of stromal cell-derived factor-1 (SDF-1) in stroke rats. We examined whether the SDF-1/CXCR4 pathway is involved in the enhanced neurogenesis and promoted behavioral recovery induced by forced limb-use in the chronic phase of stroke. The CXCR4 antagonist, AMD3100, was used to block the SDF-1/CXCR4 pathway in the ischemic rats. Brain ischemia was induced by endothelin-1. One week after ischemia, the unimpaired forelimb of rats was immobilized for 3 weeks. The proliferation, migration, and survival of DCX-positive cells in the subventricular zone (SVZ), and the dendritic complexity of DCX-positive cells in the dentate gyrus (DG), as well as the inflammatory response in the infarcted striatum were analyzed by immunohistochemistry. Functional recovery was assessed in beam-walking and water maze tests. Forced limb-use enhanced the proliferation, migration, dendritic complexity and the survival of newborn neurons. Furthermore, forced limb-use suppressed the inflammatory response and improved both motor and cognitive functions after stroke. AMD3100 significantly abrogated the enhanced neurogenesis and behavioral recovery induced by forced limb-use without influencing the inflammatory response. SDF-1/CXCR4 pathway seems to be involved in the enhancement of neurogenesis and behavioral recovery induced by post-stroke forced limb-use.

  15. The effect of pyrithioxine and pyridoxine on individual behavior, social interactions, and learning in rats malnourished in early postnatal life.

    Science.gov (United States)

    Tikal, K; Benesová, O; Franková, S

    1976-04-15

    Low protein (LP) or low calorie (LC) dietary regimens were applied in early postnatal life(1st-40th day of life) in male rats. After nutritional rehabilitation, open-field behavior in larger more illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), and smaller, less illuminated boxes (HI, high intensity stimulus), dyadic interactions, and learning ability were investigated in these animals as adults (between the 200th to 300th day of life). LP malnutrition induced an increase of open-field activity with features of sterotypy both in LI and HI situations, an increase number of intersignal reactions during learning procedures without changes in other registered criteria of learning ability (latency, number of correct responses), and an increase of aggressive behavior in pair interaction. LC rats revealed only significant inhibition in LI--open-field activity and a slightly increased number in intersignal reactions during avoidance learning. With the aim of preventing previously described long-term deviations in early malnourished rats, some groups of animals with the above-mentioned early calorie or protein deficits were treated with pyrithioxine (Encephabol Merck) or pyridoxine in 10 doses of 40 mg/kg i.p. administered in the period when nutritional rehabilitation was carried out (between the 40th--50th day of life). The treatment with pyrithioxine reduced significantly behavioral disturbances in adult LP rats except the increase of intersignal reactions which was even potentiated. Pyridoxine was less effective but normalized the increase number of intersignal reactions both in LP and LC rats. The effect of pyridoxine of adult LC rats was interesting. There was significant improvement in all registered parameters of avoidance learning and a significant increase of sexual acts was recorded.

  16. Opposing Effects of α2- and β-Adrenergic Receptor Stimulation on Quiescent Neural Precursor Cell Activity and Adult Hippocampal Neurogenesis

    Science.gov (United States)

    Prosper, Boris W.; Marathe, Swanand; Husain, Basma F. A.; Kernie, Steven G.; Bartlett, Perry F.; Vaidya, Vidita A.

    2014-01-01

    Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and β-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of β-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and β-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis. PMID:24922313

  17. Anxiety disorders in pregnancy and the postnatal period ...

    African Journals Online (AJOL)

    Anxiety disorders in pregnancy and the postnatal period. ... Continuing Medical Education ... There is a growing realisation that many women suffer from either new onset or worsening of existing anxiety disorders during pregnancy and postnatally (the perinatal period).1 The occurrence of an anxiety disorder during this time ...

  18. Treatment with soy isoflavones during early adulthood improves metabolism in early postnatally overfed rats.

    Science.gov (United States)

    Silva, Pamelli; Ribeiro, Tatiane Aparecida; Tófolo, Laize Peron; Prates, Kelly Valério; Francisco, Flávio Andrade; Silveira, Sandra da Silva; Malta, Ananda; Lopes, Denise Alves; Miranda, Rosiane Aparecida; Palma-Rigo, Kesia; Torrezan, Rosana; Mathias, Paulo Cezar de Freitas

    2018-01-01

    The incidences of obesity and related diseases have reached epidemic proportions, and new therapeutic approaches are needed. Soy isoflavones have been identified as an important dietary factor for preventing and treating metabolic dysfunction. This study examined the effects of high doses of isoflavone on glucose and fat metabolism in a model of programmed obesity and evaluated its effects on the autonomic nervous system. Litters of Wistar rats were standardized at nine pups per dam in normal litters (NL) or reduced to three pups per dam at the third day of life (P3) in small litters (SL) to induce postnatal overfeeding. Gavage with a soy bean isoflavone mixture (1 g/day) diluted in water was started at P60 and continued for 30 days. The control animals received vehicle gavage. At P90, biometric and metabolic parameters as well as direct autonomic nerve activity were measured. Increases in glycaemia and insulinaemia observed in SL rats were reduced by isoflavone treatment, which also caused lower glucose-induced insulin secretion by pancreatic islets. Sympathetic activity in the major splanchnic nerve was increased, while vagus nerve activity was reduced by isoflavone treatment. The dyslipidaemia induced by overfeeding in SL rats was restored by isoflavone treatment. The present study shows that treatment with isoflavone reduces adiposity and improves glucose and lipid metabolism. Collectively, these effects may depend on autonomic changes.

  19. The effectiveness of exercise as a treatment for postnatal depression: study protocol

    Directory of Open Access Journals (Sweden)

    Daley Amanda J

    2012-06-01

    Full Text Available Abstract Background Postnatal depression can have a substantial impact on the woman, the child and family as a whole. Thus, there is a need to examine different ways of helping women experiencing postnatal depression; encouraging them to exercise may be one way. A meta analysis found some support for exercise as an adjunctive treatment for postnatal depression but the methodological inadequacy of the few small studies included means that it is uncertain whether exercise reduces symptoms of postnatal depression. We aim to determine whether a pragmatic exercise intervention that involves one-to-one personalised exercise consultations and telephone support plus usual care in women with postnatal depression, is superior to usual care only, in reducing symptoms of postnatal depression. Methods We aim to recruit 208 women with postnatal depression in the West Midlands. Recently delivered women who meet the ICD-10 diagnosis for depression will be randomised to usual care plus exercise or usual care only. The exercise intervention will be delivered over 6 months. The primary outcome measure is difference in mean Edinburgh Postnatal Depression Scale score between the groups at six month follow-up. Outcome measures will be assessed at baseline and at six and 12 month post randomisation. Discussion Findings from the research will inform future clinical guidance on antenatal and postnatal mental health, as well as inform practitioners working with postnatal depression. Trial registration number ISRCTN84245563

  20. The radioimmunological determination of the insulin level in the early postnatal period of the pigs

    International Nuclear Information System (INIS)

    Nowak, J.; Staszak, B.; Slebodzinski, A.

    1980-01-01

    The insulin level determined by means of the radioimmunoassay, in piglets, 1 - 21 days of age revealed marked changes with age of the animals, as illustrated by the hormonal profiles. In general, the postnatal insuline profile was characterized by a quick rise in the serum hormone concentration - the postnatal hiperinsulinemia - observed already in some litters within the first 48 hours of life. The peak of the hormone concentration was followed by a decrease to a relatively constant but low level, between the third day and 10 - 14 day. In the absolute terms, the insulin concentration at 0 - 6 hours averaged from 3.3+-1.42 to 11.0+-1.44 μU/ml and then increased to the maximum from 19.8+-1.44 to 30.3+-8.81 μU/ml (means +- S.E., p<0.01) found between 12 - 36 hour of life. In some of the pigs a low or a high insulin level came by turns. Any insulin level above 16 μU/ml was classified as ''an insulin peak'' and that below 8 μU/ml as ''an insulin depression''. The frequency of the peaks and the depressions per day was the highest during the first 2 days of life, that is during the period known from the highest mortality in this species. The preliminary observation suggest that a high frequency of the insulin depressions is somewhat related to the lower vitality or to the hypoglycemia state. (author)