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Sample records for postnatal mammalian brain

  1. Postnatal brain development

    DEFF Research Database (Denmark)

    Jernigan, Terry L; Baaré, William F C; Stiles, Joan

    2011-01-01

    After birth, there is striking biological and functional development of the brain's fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact...... in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain-behavior associations in children, including genetic variation, behavioral interventions...... constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes...

  2. Postnatal brain development

    DEFF Research Database (Denmark)

    Jernigan, Terry L; Baaré, William F C; Stiles, Joan

    2011-01-01

    After birth, there is striking biological and functional development of the brain's fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact...... constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes...... in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain-behavior associations in children, including genetic variation, behavioral interventions...

  3. mammalian brain system

    Directory of Open Access Journals (Sweden)

    Alan Kania

    2014-06-01

    Full Text Available Relaxin-3, a member of the relaxin peptide family, was discovered in 2001 as a homologue of relaxin – a well-known reproductive hormone. However, it is the brain which turned out to be a major expression site of this newly discovered peptide. Both its molecular structure and expression pattern were shown to be very conserved among vertebrates. Extensive research carried out since the discovery of relaxin-3 contributed to the significant progress in our knowledge regarding this neuropeptide. The endogenous relaxin-3 receptor (RXFP3 was identified and the anatomy of the yet uncharacterized mammalian brain system was described, with nucleus incertus as the main center of relaxin-3 expression. Not only its diffusive projections throughout the whole brain, which reach various brain structures such as the hippocampus, septum, intergeniculate leaflet or amygdala, but also functional studies of the relaxin-3/RXFP3 signaling system, allowed this brain network to be classified as one of the ascending nonspecific brain systems. Thus far, research depicts the connection of relaxin-3 with phenomena such as feeding behavior, spatial memory, sleep/wake cycle or modulation of pituitary gland hormone secretion. Responsiveness of relaxin-3 neurons to stress factors and the strong orexigenic effect exerted by this peptide suggest its participation in modulation of feeding by stress, in particular of the chronic type. The discovery of relaxin-3 opened a new research field which will contribute to our better understanding of the neurobiological basis of feeding disorders.

  4. 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...

  5. Two Ancient Gene Families Are Critical for Maintenance of the Mammalian Skin Barrier in Postnatal Life.

    Science.gov (United States)

    Cangkrama, Michael; Darido, Charbel; Georgy, Smitha R; Partridge, Darren; Auden, Alana; Srivastava, Seema; Wilanowski, Tomasz; Jane, Stephen M

    2016-07-01

    The skin barrier is critical for mammalian survival in the terrestrial environment, affording protection against fluid loss, microbes, toxins, and UV exposure. Many genes indispensable for barrier formation in the embryo have been identified, but loss of these genes in adult mice does not induce barrier regression. We describe a complex regulatory network centered on two ancient gene families, the grainyhead-like (Grhl) transcription factors and the protein cross-linking enzymes (tissue transglutaminases [Tgms]), which are essential for skin permeability barrier maintenance in adult mice. Embryonic deletion of Grhl3 induces loss of Tgm1 expression, which disrupts the cornified envelope, thus preventing permeability barrier formation leading to neonatal death. However, gene deletion of Grhl3 in adult mice does not disrupt the preformed barrier, with cornified envelope integrity maintained by Grhl1 and Tgm5, which are up-regulated in response to postnatal loss of Grhl3. Concomitant deletion of both Grhl factors in adult mice induced loss of Tgm1 and Tgm5 expression, perturbation of the cornified envelope, and complete permeability barrier regression that was incompatible with life. These findings define the molecular safeguards for barrier function that accompany the transition from intrauterine to terrestrial life. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Presence of abscisic acid, a phytohormone, in the mammalian brain.

    OpenAIRE

    Le Page-Degivry, M T; Bidard, J N; Rouvier, E; Bulard, C; Lazdunski, M

    1986-01-01

    This paper reports the presence of abscisic acid, one of the most important phytohormones, in the central nervous system of pigs and rats. The identification of this hormone in brain was made after extensive purification by using a radioimmunoassay that is very specific for (+)-cis-abscisic acid. The final product of purification from mammalian brain has the same properties as authentic abscisic acid: it crossreacts in the radioimmunoassay for the phytohormone and it has the same retention pr...

  7. Intrinsic control of electroresponsive properties of transplanted mammalian brain neurons

    DEFF Research Database (Denmark)

    Hounsgaard, J; Yarom, Y

    1985-01-01

    The present study presents the first analysis of neurons in mammalian brain transplants based on intracellular recording. The results, obtained in brain slices including both donor and host tissue, showed that neuronal precursor cells in embryonic transplants retained their ability to complete...... their normal differentiation of cell-type-specific electroresponsive properties. Distortions in cell aggregation and synaptic connectivity did not affect this aspect of neuronal differentiation....

  8. On the Evolution of the Mammalian Brain.

    Science.gov (United States)

    Torday, John S; Miller, William B

    2016-01-01

    Hobson and Friston have hypothesized that the brain must actively dissipate heat in order to process information (Hobson et al., 2014). This physiologic trait is functionally homologous with the first instantation of life formed by lipids suspended in water forming micelles- allowing the reduction in entropy (heat dissipation). This circumvents the Second Law of Thermodynamics permitting the transfer of information between living entities, enabling them to perpetually glean information from the environment, that is felt by many to correspond to evolution per se. The next evolutionary milestone was the advent of cholesterol, embedded in the cell membranes of primordial eukaryotes, facilitating metabolism, oxygenation and locomotion, the triadic basis for vertebrate evolution. Lipids were key to homeostatic regulation of calcium, forming calcium channels. Cell membrane cholesterol also fostered metazoan evolution by forming lipid rafts for receptor-mediated cell-cell signaling, the origin of the endocrine system. The eukaryotic cell membrane exapted to all complex physiologic traits, including the lung and brain, which are molecularly homologous through the function of neuregulin, mediating both lung development and myelinization of neurons. That cooption later exapted as endothermy during the water-land transition (Torday, 2015a), perhaps being the functional homolog for brain heat dissipation and conscious/mindful information processing. The skin and brain similarly share molecular homologies through the "skin-brain" hypothesis, giving insight to the cellular-molecular "arc" of consciousness from its unicellular origins to integrated physiology. This perspective on the evolution of the central nervous system clarifies self-organization, reconciling thermodynamic and informational definitions of the underlying biophysical mechanisms, thereby elucidating relations between the predictive capabilities of the brain and self-organizational processes.

  9. On the evolution of the mammalian brain

    Directory of Open Access Journals (Sweden)

    John Steven Torday

    2016-04-01

    Full Text Available Hobson and Friston have hypothesized that the brain must actively dissipate heat in order to process information (Virtual reality and consciousness inference in dreaming. Front Psychol. 2014 Oct 9;5:1133.. This physiologic trait is functionally homologous with the first instantation of life formed by lipids suspended in water forming micelles- allowing the reduction in entropy (heat dissipation, circumventing the Second Law of Thermodynamics permitting the transfer of information between living entities, enabling them to perpetually glean information from the environment (= evolution. The next evolutionary milestone was the advent of cholesterol, embedded in the cell membranes of primordial eukaryotes, facilitating metabolism, oxygenation and locomotion, the triadic basis for vertebrate evolution. Lipids were key to homeostatic regulation of calcium, forming calcium channels. Cell membrane cholesterol also fostered metazoan evolution by forming lipid rafts for receptor-mediated cell-cell signaling, the origin of the endocrine system. The eukaryotic cell membrane exapted to all complex physiologic traits, including the lung and brain, which are molecularly homologous through the function of neuregulin, mediating both lung development and myelinization of neurons. That cooption later exapted as endothermy during the water-land transition (Torday JS. A Central Theory of Biology. Med Hypotheses. 2015 Jul;85(1:49-57, perhaps being the functional homolog for brain heat dissipation and consciousness/mind. The skin and brain similarly share molecular homologies through the ‘skin-brain’ hypothesis, giving insight to the cellular-molecular ‘arc’ of consciousness from its unicellular origins to integrated physiology. This perspective on the evolution of the central nervous system clarifies self-organization, reconciling thermodynamic and informational definitions of the underlying biophysical mechanisms, thereby elucidating relations between the

  10. Damage and repair of irradiated mammalian brain

    International Nuclear Information System (INIS)

    Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K.

    1989-07-01

    We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as ''vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs

  11. Damage and repair of irradiated mammalian brain

    Energy Technology Data Exchange (ETDEWEB)

    Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K. (Lawrence Berkeley Lab., CA (USA); Stanford Univ., CA (USA). Medical Center; Brookside Hospital, San Pablo, CA (USA))

    1989-07-01

    We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs.

  12. Molecular biology of the mammalian brain

    International Nuclear Information System (INIS)

    Morrison, M.R.; Griffin, W.S.T.

    1985-01-01

    The authors' characterization of abundant mRNAs by analysis of their in vitro translation products has provided detailed information on the changes in steady-state mRNA levels taking place during brain and neuroblastoma differentiation as well as on more general aspects of mRNA structure and utilization in the nervous system. Quantitation of specific mRNAs using radiolabelled recombinant DNA probes has confirmed that the measurements of translationally active tubulin and actin mRNAs by this method are indeed an accurate indication of their steady-state levels. The technology is now available to characterize neuropathology at the cellular level. Analysis of mRNA changes in diseased brain are of obvious relevance in documenting gross pathological changes in transcription patterns. In situ hybridization and immunohistochemistry can now be used, perhaps even in combination with computer reconstruction to investigate more critically the specific cell losses so characteristic of diseases such as Huntington's, Parkinson's, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer's. In situ hybridization of probes to mRNAs encoding specific neurotransmitter enzymes and abundant ''housekeeping'' proteins can now be used to determine whether the remaining cells in affected brain areas are transcriptionally normal. Furthermore, this technique can also be used to document the transcriptional changes in cell types not presently identified as compromised and thus will pinpoint more precisely the initial cell targets of disease

  13. The neuroanatomy of the kisspeptin system in the mammalian brain

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Simonneaux, Valerie

    2008-01-01

    , little data are available about the localization of kisspeptin neurons in the brain, and in particular the projection patterns of kisspeptin containing axons implicated in regulation of the hypothalamo-pituitary gonadal axis. This review covers the current information about the localization of kisspeptin...... neurons in the mammalian brain and discusses the facts and artifacts of the methods of their detection. The available data suggest that kisspeptins are synthesized in neurons in the anteroventral periventricular nucleus and the arcuate nucleus. Both populations are considered to be involved in control...

  14. Presence of abscisic acid, a phytohormone, in the mammalian brain

    International Nuclear Information System (INIS)

    Le Page-Degivry, M.T.; Bidard, J.N.; Rouvier, E.; Bulard, C.; Lazdunski, M.

    1986-01-01

    This paper reports the presence of abscisic acid, one of the most important phytohormones, in the central nervous system of pigs and rats. The identification of this hormone in brain was made after extensive purification by using a radioimmunoassay that is very specific for (+)-cis-abscisic acid. The final product of purification from mammalian brain has the same properties as authentic abscisic acid: it crossreacts in the radioimmunoassay for the phytohormone and it has the same retention properties and the same gas chromatography/mass spectrometry characteristics. Moreover, like (+)-cis-abscisic acid itself, the brain factor inhibits stomatal apertures of abaxial epidermis strips of Setcreasea purpurea Boom (Commelinaceae). The presence of abscisic acid conjugates that are present in plants has also been identified in brain

  15. Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

    Science.gov (United States)

    Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

    2015-04-01

    Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

  16. Oxytocin receptor ligand binding in embryonic tissue and postnatal brain development of the C57BL/6J mouse

    Directory of Open Access Journals (Sweden)

    Elizabeth eHammock

    2013-12-01

    Full Text Available Oxytocin (OXT has drawn increasing attention as a developmentally relevant neuropeptide given its role in the brain regulation of social behavior. It has been suggested that OXT plays an important role in the infant brain during caregiver attachment in nurturing familial contexts, but there is incomplete experimental evidence. Mouse models of OXT system genes have been particularly informative for the role of the OXT system in social behavior, however, the developing brain areas that could respond to ligand activation of the OXT receptor (OXTR have yet to be identified in this species. Here we report new data revealing dynamic ligand-binding distribution of OXTR in the developing mouse brain. Using male and female C57BL/6J mice at postnatal days (P 0, 7, 14, 21, 35, and 60 we quantified OXTR ligand binding in several brain areas which changed across development. Further, we describe OXTR ligand binding in select tissues of the near-term whole embryo at E18.5. Together, these data aid in the interpretation of findings in mouse models of the OXT system and generate new testable hypotheses for developmental roles for OXT in mammalian systems. We discuss our findings in the context of developmental disorders (including autism, attachment biology, and infant physiological regulation.

  17. Long-lasting masculinizing effects of postnatal androgens on myelin governed by the brain androgen receptor

    Science.gov (United States)

    Abi Ghanem, Charly; Degerny, Cindy; Hussain, Rashad; Liere, Philippe; Pianos, Antoine; Tourpin, Sophie; Habert, René; Schumacher, Michael

    2017-01-01

    The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating. Androgen levels, analyzed by gas chromatography/tandem-mass spectrometry, were higher in males than in females during this period. Treating male pups with flutamide, an androgen receptor (AR) antagonist, or female pups with 5α-dihydrotestosterone (5α-DHT), revealed the importance of postnatal androgens in masculinizing myelin and their persistent effect into adulthood. A key role of the brain AR in establishing the sexual phenotype of myelin was demonstrated by its conditional deletion. Our results uncover a new persistent effect of postnatal AR signaling, with implications for neurodevelopmental disorders and sex differences in multiple sclerosis. PMID:29107990

  18. Romantic love: a mammalian brain system for mate choice.

    Science.gov (United States)

    Fisher, Helen E; Aron, Arthur; Brown, Lucy L

    2006-12-29

    Mammals and birds regularly express mate preferences and make mate choices. Data on mate choice among mammals suggest that this behavioural 'attraction system' is associated with dopaminergic reward pathways in the brain. It has been proposed that intense romantic love, a human cross-cultural universal, is a developed form of this attraction system. To begin to determine the neural mechanisms associated with romantic attraction in humans, we used functional magnetic resonance imaging (fMRI) to study 17 people who were intensely 'in love'. Activation specific to the beloved occurred in the brainstem right ventral tegmental area and right postero-dorsal body of the caudate nucleus. These and other results suggest that dopaminergic reward and motivation pathways contribute to aspects of romantic love. We also used fMRI to study 15 men and women who had just been rejected in love. Preliminary analysis showed activity specific to the beloved in related regions of the reward system associated with monetary gambling for uncertain large gains and losses, and in regions of the lateral orbitofrontal cortex associated with theory of mind, obsessive/compulsive behaviours and controlling anger. These data contribute to our view that romantic love is one of the three primary brain systems that evolved in avian and mammalian species to direct reproduction. The sex drive evolved to motivate individuals to seek a range of mating partners; attraction evolved to motivate individuals to prefer and pursue specific partners; and attachment evolved to motivate individuals to remain together long enough to complete species-specific parenting duties. These three behavioural repertoires appear to be based on brain systems that are largely distinct yet interrelated, and they interact in specific ways to orchestrate reproduction, using both hormones and monoamines. Romantic attraction in humans and its antecedent in other mammalian species play a primary role: this neural mechanism motivates

  19. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly

    Directory of Open Access Journals (Sweden)

    Deepa Bhartiya

    2016-01-01

    Full Text Available Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes. These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility.

  20. Postnatal brain and skull growth in an Apert syndrome mouse model

    Science.gov (United States)

    Hill, Cheryl A.; Martínez-Abadías, Neus; Motch, Susan M.; Austin, Jordan R.; Wang, Yingli; Jabs, Ethylin Wang; Richtsmeier, Joan T.; Aldridge, Kristina

    2012-01-01

    Craniofacial and neural tissues develop in concert throughout pre- and postnatal growth. FGFR-related craniosynostosis syndromes, such as Apert syndrome (AS), are associated with specific phenotypes involving both the skull and the brain. We analyzed the effects of the FGFR P253R mutation for Apert syndrome using the Fgfr2+/P253R mouse to evaluate the effects of this mutation on these two tissues over the course of development from day of birth (P0) to postnatal day 2 (P2). Three-dimensional magnetic resonance microscopy and computed tomography images were acquired from Fgfr2+/P253R mice and unaffected littermates at P0 (N=28) and P2 (N=23). 3D coordinate data for 23 skull and 15 brain landmarks were statistically compared between groups. Results demonstrate that the Fgfr2+/P253R mice show reduced growth in the facial skeleton and the cerebrum, while the height and width of the neurocranium and caudal regions of the brain show increased growth relative to unaffected littermates. This localized correspondence of differential growth patterns in skull and brain point to their continued interaction through development and suggest that both tissues display divergent postnatal growth patterns relative to unaffected littermates. However, the change in the skull-brain relationship from P0 to P2 implies that each tissue affected by the mutation retains a degree of independence, rather than one tissue directing the development of the other. PMID:23495236

  1. Characterization of piRNAs across postnatal development in mouse brain

    KAUST Repository

    Ghosheh, Yanal; Seridi, Loqmane; Ryu, Tae Woo; Takahashi, Hazuki; Orlando, Valerio; Carninci, Piero; Ravasi, Timothy

    2016-01-01

    PIWI-interacting RNAs (piRNAs) are responsible for maintaining the genome stability by silencing retrotransposons in germline tissues– where piRNAs were first discovered and thought to be restricted. Recently, novel functions were reported for piRNAs in germline and somatic cells. Using deep sequencing of small RNAs and CAGE of postnatal development of mouse brain, we identified piRNAs only in adult mouse brain. These piRNAs have similar sequence length as those of MILI-bound piRNAs. In addition, we predicted novel candidate regulators and putative targets of adult brain piRNAs.

  2. Characterization of piRNAs across postnatal development in mouse brain

    KAUST Repository

    Ghosheh, Yanal

    2016-04-26

    PIWI-interacting RNAs (piRNAs) are responsible for maintaining the genome stability by silencing retrotransposons in germline tissues– where piRNAs were first discovered and thought to be restricted. Recently, novel functions were reported for piRNAs in germline and somatic cells. Using deep sequencing of small RNAs and CAGE of postnatal development of mouse brain, we identified piRNAs only in adult mouse brain. These piRNAs have similar sequence length as those of MILI-bound piRNAs. In addition, we predicted novel candidate regulators and putative targets of adult brain piRNAs.

  3. 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

  4. Tritium toxicity in postnatally developing brain: Effects of single administration on nucleic acids and protein

    International Nuclear Information System (INIS)

    Bhatia, A.L.; Saraswat, A.

    1988-01-01

    The brains of postnatally developing mice were studied at one, two, three, four, five and six weeks of age after injecting one day old neonates (1.95 ± 0.35 g) with 11.1 kBq and 111 kBq/ml of bondy water. The HTO-exposed developing animals though do not show any significant decline in their brain and body weight, their DNA concentration was found significantly depleted at one week by 19% after the treatment with 111 kBq dose and subsequently recovered by six week reaching 93% of the control. Protein concentration showed significant deficit in both the dose groups at all the postnatal invervals. Protein/DNA ratio increased in one and two weeks old mice and reduced from weeks onward. RNA/DNA ratio has also been found consistently low in irradiated groups. (orig.) [de

  5. Prenatal and Postnatal Medical Conditions and the Risk of Brain Tumors in Children and Adolescents

    DEFF Research Database (Denmark)

    Tettamanti, Giorgio; Shu, Xiaochen; Adel Fahmideh, Maral

    2017-01-01

    BACKGROUND: Previous studies have evaluated the effect of medical diagnostic radiation on brain tumors. Recent cohort studies have reported an increased risk associated with exposure to head CT scans. METHODS: Information regarding medical conditions, including prenatal and postnatal exposure...... to medical diagnostic radiation, was obtained from CEFALO, a multicenter case-control study performed in Denmark, Norway, Sweden, and Switzerland through face-to-face interview. Eligible cases of childhood and adolescent brain tumors (CABT) were ages 7 to 19 years, diagnosed between January 1, 2004...... and August 31, 2008, and living in the participating countries (n = 352). The cases were matched by age, sex, and region to 646 population-based controls. RESULTS: Prenatal exposure to medical diagnostic radiation and postnatal exposure to X-rays were not associated with CABTs. A higher risk estimate...

  6. Neural stem cells show bidirectional experience-dependent plasticity in the perinatal mammalian brain.

    Science.gov (United States)

    Kippin, Tod E; Cain, Sean W; Masum, Zahra; Ralph, Martin R

    2004-03-17

    Many of the effects of prenatal stress on the endocrine function, brain morphology, and behavior in mammals can be reversed by brief sessions of postnatal separation and handling. We have tested the hypothesis that the effects of both the prenatal and postnatal experiences are mediated by negative and positive regulation of neural stem cell (NSC) number during critical stages in neurodevelopment. We used the in vitro clonal neurosphere assay to quantify NSCs in hamsters that had experienced prenatal stress (maternal restraint stress for 2 hr per day, for the last 7 d of gestation), postnatal handling (maternal-offspring separation for 15 min per day during postnatal days 1-21), orboth. Prenatal stress reduced the number of NSCs derived from the subependyma of the lateral ventricle. The effect was already present at postnatal day 1 and persisted into adulthood (at least 14 months of age). Similarly, prenatal stress reduced in vivo proliferation in the adult subependyma of the lateral ventricle. Conversely, postnatal handling increased NSC number and reversed the effect of prenatal stress. The effects of prenatal stress on NSCs and proliferation and the effect of postnatal handling on NSCs did not differ between male and females. The findings demonstrate that environmental factors can produce changes in NSC number that are present at birth and endure into late adulthood. These changes may underlie some of the behavioral effects produced by prenatal stress and postnatal handling.

  7. Refining the Role of 5-HT in Postnatal Development of Brain Circuits

    Directory of Open Access Journals (Sweden)

    Anne Teissier

    2017-05-01

    Full Text Available Changing serotonin (5-hydroxytryptamine, 5-HT brain levels during critical periods in development has long-lasting effects on brain function, particularly on later anxiety/depression-related behaviors in adulthood. A large part of the known developmental effects of 5-HT occur during critical periods of postnatal life, when activity-dependent mechanisms remodel neural circuits. This was first demonstrated for the maturation of sensory brain maps in the barrel cortex and the visual system. More recently this has been extended to the 5-HT raphe circuits themselves and to limbic circuits. Recent studies overviewed here used new genetic models in mice and rats and combined physiological and structural approaches to provide new insights on the cellular and molecular mechanisms controlled by 5-HT during late stages of neural circuit maturation in the raphe projections, the somatosensory cortex and the visual system. Similar mechanisms appear to be also involved in the maturation of limbic circuits such as prefrontal circuits. The latter are of particular relevance to understand the impact of transient 5-HT dysfunction during postnatal life on psychiatric illnesses and emotional disorders in adult life.

  8. Dynamic changes in DNA demethylation in the tree shrew (Tupaia belangeri chinensis) brain during postnatal development and aging.

    Science.gov (United States)

    Wei, Shu; Hua, Hai-Rong; Chen, Qian-Quan; Zhang, Ying; Chen, Fei; Li, Shu-Qing; Li, Fan; Li, Jia-Li

    2017-03-18

    Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews ( Tupaia belangeri chinensis ). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.

  9. Possible involvement of SINEs in mammalian-specific brain formation.

    Science.gov (United States)

    Sasaki, Takeshi; Nishihara, Hidenori; Hirakawa, Mika; Fujimura, Koji; Tanaka, Mikiko; Kokubo, Nobuhiro; Kimura-Yoshida, Chiharu; Matsuo, Isao; Sumiyama, Kenta; Saitou, Naruya; Shimogori, Tomomi; Okada, Norihiro

    2008-03-18

    Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINEs), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalian-specific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.

  10. Postnatal development of EEG patterns, catecholamine contents and myelination, and effect of hyperthyroidism in Suncus brain.

    Science.gov (United States)

    Takeuchi, T; Sitizyo, K; Harada, E

    1998-03-01

    The postnatal development of the central nervous system (CNS) in house musk shrew in the early stage of maturation was studied. The electroencephalogram (EEG) and visual evoked potential (VEP) in association with catecholamine contents and myelin basic protein (MBP) immunoreactivity were carried out from the 1st to the 20th day of postnatal age. Different EEG patterns which were specific to behavioral states (awake and drowsy) were first recorded on the 5th day, and the total power which was obtained by power spectrum analysis increased after this stage. The latencies of all peaks in VEP markedly shortened between the 5th and the 7th day. Noradrenalin (NA) content of the brain showed a slight increase after the 3rd day, and reached maximum levels on the 7th day, which was delayed a few days compared to dopamine (DA). In hyperthyroidism, the peak latency of VEP was shortened and biosynthesis of NA in cerebral cortex and DA in hippocampus was accelerated. The most obvious change in MBP-immunoreactivity of the telencephalon occurred from the 7th to the 10th day. These morphological changes in the brain advanced at the identical time-course to those in the electrophysiological development and increment of DA and NA contents.

  11. Vertebrate brains and evolutionary connectomics: on the origins of the mammalian ‘neocortex’

    Science.gov (United States)

    Karten, Harvey J.

    2015-01-01

    The organization of the non-mammalian forebrain had long puzzled neurobiologists. Unlike typical mammalian brains, the telencephalon is not organized in a laminated ‘cortical’ manner, with distinct cortical areas dedicated to individual sensory modalities or motor functions. The two major regions of the telencephalon, the basal ventricular ridge (BVR) and the dorsal ventricular ridge (DVR), were loosely referred to as being akin to the mammalian basal ganglia. The telencephalon of non-mammalian vertebrates appears to consist of multiple ‘subcortical’ groups of cells. Analysis of the nuclear organization of the avian brain, its connections, molecular properties and physiology, and organization of its pattern of circuitry and function relative to that of mammals, collectively referred to as ‘evolutionary connectomics’, revealed that only a restricted portion of the BVR is homologous to the basal ganglia of mammals. The remaining dorsal regions of the DVR, wulst and arcopallium of the avian brain contain telencephalic inputs and outputs remarkably similar to those of the individual layers of the mammalian ‘neocortex’, hippocampus and amygdala, with instances of internuclear connections strikingly similar to those found between cortical layers and within radial ‘columns’ in the mammalian sensory and motor cortices. The molecular properties of these ‘nuclei’ in birds and reptiles are similar to those of the corresponding layers of the mammalian neocortex. The fundamental pathways and cell groups of the auditory, visual and somatosensory systems of the thalamus and telencephalon are homologous at the cellular, circuit, network and gene levels, and are of great antiquity. A proposed altered migration of these homologous neurons and circuits during development is offered as a mechanism that may account for the altered configuration of mammalian telencephalae. PMID:26554047

  12. Postnatal experiences influence how the brain integrates information from different senses

    Directory of Open Access Journals (Sweden)

    Barry E Stein

    2009-09-01

    Full Text Available Sensory Processing Disorder (SPD is characterized by anomalous reactions to, and integration of, sensory cues. Although the underlying etiology of SPD is unknown, one brain region likely to reflect these sensory and behavioral anomalies is the Superior Colliculus (SC; a structure involved in the synthesis of information from multiple sensory modalities and the control of overt orientation responses. In this review we describe normal functional properties of this structure, the manner in which its individual neurons integrate cues from different senses, and the overt SC-mediated behaviors that are believed to manifest this “multisensory integration.” Of particular interest here is how SC neurons develop their capacity to engage in multisensory integration during early postnatal life as a consequence of early sensory experience, and that it is the intimate communication between cortex and the midbrain makes this developmental process possible.

  13. Vitamin-C protect ethanol induced apoptotic neuro degeneration in postnatal rat brain

    International Nuclear Information System (INIS)

    Naseer, M.I.; Najeebullah; Ikramullah; Zubair, H.; Hassan, M.; Yang, B.C.

    2010-01-01

    Objective: To evaluate ethanol effects to induced activation of caspsae-3, and to observe the protective effects of Vitamin C (vit-C) on ethanol-induced apoptotic neuro degeneration in rat cortical area of brain. Methodology: Administration of a single dose of ethanol in 7-d postnatal (P7) rats triggers activation of caspase-3 and widespread apoptotic neuronal death. Western blot analysis, cells counting and Nissl staining were used to elucidate possible protective effect of vit-C against ethanol-induced apoptotic neuro degeneration in brain. Results: The results showed that ethanol significantly increased caspase-3 expression and neuronal apoptosis. Furthermore, the co-treatment of vit-C along with ethanol showed significantly decreased expression of caspase-3 as compare to control group. Conclusion: Our findings indicate that vit-C can prevent some of the deleterious effect of ethanol on developing rat brain when given after ethanol exposure and can be used as an effective protective agent for Fetal Alcohol Syndrome (FAS). (author)

  14. Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat.

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    Emily J Camm

    Full Text Available In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1 x day(-1, with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1 x day(-1 and 100 mg x kg(-1 x day(-1, respectively, on postnatal days 1-6 (P1-6. Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3 vs. 564.0±20.0 mm(3, the soma volume of neurons in the CA1 (1172.6±30.4 µm(3 vs. 1002.4±11.8 µm(3 and in the dentate gyrus (525.9±27.2 µm(3 vs. 421.5±24.6 µm(3 of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%. Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3, and soma volume of neurons in the CA1 (1157.5±42.4 µm(3 and the dentate gyrus (536.1±27.2 µm(3. Hsp70 protein expression was unaltered in the cortex (+9%, however, 4-HNE (+95% and NT (+24% protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22% and in the hippocampus (NT: +35%. Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended.

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

    Science.gov (United States)

    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

  16. Effect of Irradiation Maternal Diets on the Post-natal Development of Brain Rat Pups

    International Nuclear Information System (INIS)

    Hasan, S.S.

    2005-09-01

    Full text: Effect of Protein-calorie malnutrition was studied on the pups born to mothers receiving either irradiated normal diet (consisted equal parts of gram and wheat) or irradiation low protein diet (consisted one part of normal diet and three parts of heat). Level of DNA, RNA and protein content were found markedly reduced in the brain of irradiated low protein diet fed pups than in the pups fed on the irradiated normal diet. Glucose 6-phosphate dehydrogenase activity was found lower while catalase and lipid peroxidation activity were higher in the pups given irradiated low protein diet, compared whit the pups fed irradiated normal diet. On the whole both the irradiated low protein diet as well as irradiated normal diet fed pups showed higher index of biochemical changes than in the unirradiated low protein diet fed pups. Post-natal mortality was 60% in the pups given irradiated low protein diet, whereas the pups fed on the irradiated normal diet and unirradiated low protein diet did not show any death. The study given evidence that feeding of the irradiated low protein diet interferes more with the development of brain compared with the pups fed on irradiated normal diet

  17. {sup 26}Al incorporation into the brain of rat fetuses through the placental barrier and subsequent metabolism in postnatal development

    Energy Technology Data Exchange (ETDEWEB)

    Yumoto, Sakae, E-mail: yumoto-s@viola.ocn.ne.j [Yumoto Institute of Neurology, Kawadacho 6-11, Shinjuku-ku, Tokyo 162-0054 (Japan); Nagai, Hisao [College of Humanities and Sciences, Nihon University, Tokyo (Japan); Kakimi, Shigeo [Faculty of Medicine, Nihon University, Tokyo (Japan); Matsuzaki, Hiroyuki [School of Engineering, The University of Tokyo, Tokyo (Japan)

    2010-04-15

    Aluminium (Al) inhibits prenatal and postnatal development of the brain. We used {sup 26}Al as a tracer, and measured {sup 26}Al incorporation into rat fetuses through the placental barrier by accelerator mass spectrometry (AMS). From day 15 to day 18 of gestation, {sup 26}AlCl{sub 3} was subcutaneously injected into pregnant rats. Considerable amounts of {sup 26}Al were measured in the tissues of newborn rats immediately after birth. The amounts of {sup 26}Al in the liver and kidneys decreased rapidly during postnatal development. However, approximately 15% of {sup 26}Al incorporated into the brain of fetuses remained in the brain of adult rats 730 days after birth.

  18. Extending the scope of neuropeptidomics in the mammalian brain

    Directory of Open Access Journals (Sweden)

    Xiaozhe Zhang

    2014-06-01

    Full Text Available Neuropeptides are signaling molecules of intermediate size that are involved in neurotransmission and endocrine regulation. Complete monitoring of neuropeptides using neuropeptidomics approaches remains an important goal for describing targeted physiological regulation pathways. Considerable effort has been expended, particularly in terms of technique and methodology development, to extend the scope of neuropeptidomics. The capability of peptide characterization has been gradually improved, thus responding to increasing demands for broad detection and determination of various peptides. In this review, we discuss some achievements for the improvement of peptide identification coverage and their application for brain diseases and studying consequences of drug applications.

  19. Emotional Arousal and Multiple Memory Systems in the Mammalian Brain

    Directory of Open Access Journals (Sweden)

    Mark G. Packard

    2012-03-01

    Full Text Available Emotional arousal induced by stress and/or anxiety can exert complex effects on learning and memory processes in mammals. Recent studies have begun to link study of the influence of emotional arousal on memory with earlier research indicating that memory is organized in multiple systems in the brain that differ in terms of the type of memory they mediate. Specifically, these studies have examined whether emotional arousal may have a differential effect on the cognitive and stimulus-response habit memory processes subserved by the hippocampus and dorsal striatum, respectively. Evidence indicates that stress or the peripheral injection of anxiogenic drugs can bias animals and humans towards the use of striatal-dependent habit memory in dual-solution tasks in which both hippocampal and stritatal-based strategies can provide an adequate solution. A bias towards the use of habit memory can also be produced by intra-basolateral amygdala administration of anxiogenic drugs, consistent with the well documented role of efferent projections of this brain region in mediating the modulatory influence of emotional arousal on memory. In some learning situations, the bias towards the use of habit memory produced by emotional arousal appears to result from an impairing effect on hippocampus-dependent cognitive memory. Further research examining the neural mechanisms linking emotion and the relative use of multiple memory systems should prove useful in view of the potential role for maladaptive habitual behaviors in various human psychopathologies.

  20. The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain.

    Science.gov (United States)

    Burchett, Scott A; Hicks, T Philip

    2006-08-01

    The trace amines are a structurally related group of amines and their isomers synthesized in mammalian brain and peripheral nervous tissues. They are closely associated metabolically with the dopamine, noradrenaline and serotonin neurotransmitter systems in mammalian brain. Like dopamine, noradrenaline and serotonin the trace amines have been implicated in a vast array of human disorders of affect and cognition. The trace amines are unique as they are present in trace concentrations, exhibit high rates of metabolism and are distributed heterogeneously in mammalian brain. While some are synthesized in their parent amine neurotransmitter systems, there is also evidence to suggest other trace amines may comprise their own independent neurotransmitter systems. A substantial body of evidence suggests that the trace amines may play very significant roles in the coordination of biogenic amine-based synaptic physiology. At high concentrations, they have well-characterized presynaptic "amphetamine-like" effects on catecholamine and indolamine release, reuptake and biosynthesis; at lower concentrations, they possess postsynaptic modulatory effects that potentiate the activity of other neurotransmitters, particularly dopamine and serotonin. The trace amines also possess electrophysiological effects that are in opposition to these neurotransmitters, indicating to some researchers the existence of receptors specific for the trace amines. While binding sites or receptors for a few of the trace amines have been advanced, the absence of cloned receptor protein has impeded significant development of their detailed mechanistic roles in the coordination of catecholamine and indolamine synaptic physiology. The recent discovery and characterization of a family of mammalian G protein-coupled receptors responsive to trace amines such as beta-phenylethylamine, tyramine, and octopamine, including socially ingested psychotropic drugs such as amphetamine, 3,4-methylenedioxymethamphetamine, N

  1. DNA content of rodent brains during maturation and aging, and autoradiography of postnatal DNA synthesis in monkey brain

    International Nuclear Information System (INIS)

    Howard, E.

    1973-01-01

    [ 3 H]Thymidine is taken up by cells synthesizing DNA prepatory to cell division and remains incorporated in the DNA molecules as a lasting radioactive cell marker unless diluted out by repeated cell divisions. With the mouse and rat, histological studies after [ 3 H]thymidine injections have demonstrated that the cells of the external granular layer of the cerebellum proliferate abundantly during the first 2 weeks of postnatal life. Development of the primate brain is a gradual process extending over a much longer time than is required in the rodent. Despite the relative histological maturity of the monkey cerebellum at birth, the cells of the external granular layer are still actively synthesizing DNA at this time. Two monkeys were given [ 3 H]thymidine at birth and killed within 4 hours. Intense radioactivity was present in the cells of the external granular layer. Cells near the Prukinje perikarya were rather frequently labelled in this monkey, as described by Miale and Sidman in the mouse. In the molecular layer and in the body of the granular layer, relatively few cells were labelled. The labelling was present throughout the cerebellum, although the number of cells labelled varied from one microscopic field to another

  2. Increasing N-acetylaspartate in the Brain during Postnatal Myelination Does Not Cause the CNS Pathologies of Canavan Disease

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    Abhilash P. Appu

    2017-06-01

    Full Text Available Canavan disease is caused by mutations in the gene encoding aspartoacylase (ASPA, a deacetylase that catabolizes N-acetylaspartate (NAA. The precise involvement of elevated NAA in the pathogenesis of Canavan disease is an ongoing debate. In the present study, we tested the effects of elevated NAA in the brain during postnatal development. Mice were administered high doses of the hydrophobic methyl ester of NAA (M-NAA twice daily starting on day 7 after birth. This treatment increased NAA levels in the brain to those observed in the brains of Nur7 mice, an established model of Canavan disease. We evaluated various serological parameters, oxidative stress, inflammatory and neurodegeneration markers and the results showed that there were no pathological alterations in any measure with increased brain NAA levels. We examined oxidative stress markers, malondialdehyde content (indicator of lipid peroxidation, expression of NADPH oxidase and nuclear translocation of the stress-responsive transcription factor nuclear factor (erythroid-derived 2-like 2 (NRF-2 in brain. We also examined additional pathological markers by immunohistochemistry and the expression of activated caspase-3 and interleukin-6 by Western blot. None of the markers were increased in the brains of M-NAA treated mice, and no vacuoles were observed in any brain region. These results show that ASPA expression prevents the pathologies associated with excessive NAA concentrations in the brain during postnatal myelination. We hypothesize that the pathogenesis of Canavan disease involves not only disrupted NAA metabolism, but also excessive NAA related signaling processes in oligodendrocytes that have not been fully determined and we discuss some of the potential mechanisms.

  3. Mammalian collection on Noah's Ark: the effects of beauty, brain and body size.

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    Daniel Frynta

    Full Text Available The importance of today's zoological gardens as the so-called "Noah's Ark" grows as the natural habitat of many species quickly diminishes. Their potential to shelter a large amount of individuals from many species gives us the opportunity to reintroduce a species that disappeared in nature. However, the selection of animals to be kept in zoos worldwide is highly selective and depends on human decisions driven by both ecological criteria such as population size or vulnerability and audience-driven criteria such as aesthetic preferences. Thus we focused our study on the most commonly kept and bred animal class, the mammals, and we asked which factors affect various aspects of the mammalian collection of zoos. We analyzed the presence/absence, population size, and frequency per species of each of the 123 mammalian families kept in the worldwide zoo collection. Our aim was to explain these data using the human-perceived attractiveness of mammalian families, their body weight, relative brain size and species richness of the family. In agreement with various previous studies, we found that the body size and the attractiveness of mammals significantly affect all studied components of the mammalian collection of zoos. There is a higher probability of the large and attractive families to be kept. Once kept, these animals are presented in larger numbers in more zoos. On the contrary, the relative mean brain size only affects the primary selection whether to keep the family or not. It does not affect the zoo population size or the number of zoos that keep the family.

  4. Enzymatic method for the sensitive demonstration of postnatal effects caused by prenatal X-irradiation in mouse brain

    International Nuclear Information System (INIS)

    Weber, L.W.D.; Schmahl, W.G.; Kriegel, H.

    1982-01-01

    We have investigated the activities (per gram of wet tissue) of mouse brain acetylcholinesterase and Na, K-ATPase, with respect to the effects brought about by a prenatal X-ray dose. Pregnant NMRI mice received an X-ray dose of 0.24, 0.49, 0.95 or 1.9 Gy each on the 12th day of gestation. Investigations on the offspring were performed on the day of birth and the postnatal days 2, 5, 8, 12, 16, 23, 34, 48 and 64, respectively. The brain weights were reduced by the X-ray treatment dose - dependently and without recovery. This was well discernible after 0.24 Gy and reached about 40% reduction after 1.9 Gy. There were significant differences between irradiated and control enzyme activities on most of the days examined. On the 48th postnatal day both enzymes' activities were thoroughly elevated after 0.24 and 0.49 Gy. This could be reproduced in another test series with 0.49 Gy, but vanished when enzyme activities were related to the brain protein contents. As a more reliable parameter of the developmental age brain weights were compared to the corresponding enzyme activities. (orig./MG)

  5. The formation of tigroid substance during postnatal maturation of the brain of mice after pre- and perinatal X-irradiation

    International Nuclear Information System (INIS)

    Konermann, G.; Schwald, I.

    1980-01-01

    Using Nissl stained slices of postnatal brain, tigroid formation in neurons of the cortex, thalamus, cerebellum, hippocampus, gyrus dentatus and nucleus mot. trigemini was examined in X-irradiated mice. Following exposure on days 13, 16, 18,5 or 22 post conception with doses ranging grom 0.5 Gy to 3.0 Gy tigroid formation was studied by means of a selective microphotometrical measurement technique. After irradiation, a fluctuating diminution in the tigroid density was observed in relation to the controls. It was dependent both on the dose and on the stage of development during exposure. In several brain regions fluctuating tigroid responses, being most pronounced during the critical periods of postnatal brain maturation, resulted in a longterm compensation of a deficit in the tigroid density after irradiation with 0.5 Gy. After the higher doses the density diminution was either not compensated or was progressive. The late tigroid responses decrease from irradiation on day 13 p.c. to irradiation day 22 p.c. Hence, this type of late maturation impairment was either extended through several cell generations or it was induced to a lesser degree in the early postmitotic neurons. Changes in the total RNA-content of the brain are concomitant with the third week after birth. The tigroid reactions were interpreted as a chain of interdependent processes of retardation and stabilization. Accordingly, to obtain a better understanding of long-term maturation defects, a comprehensive evaluation of the whole chain of events will be required. (orig.) [de

  6. Effect of alternate energy substrates on mammalian brain metabolism during ischemic events.

    Science.gov (United States)

    Koppaka, S S; Puchowicz; LaManna, J C; Gatica, J E

    2008-01-01

    Regulation of brain metabolism and cerebral blood flow involves complex control systems with several interacting variables at both cellular and organ levels. Quantitative understanding of the spatially and temporally heterogeneous brain control mechanisms during internal and external stimuli requires the development and validation of a computational (mathematical) model of metabolic processes in brain. This paper describes a computational model of cellular metabolism in blood-perfused brain tissue, which considers the astrocyte-neuron lactate-shuttle (ANLS) hypothesis. The model structure consists of neurons, astrocytes, extra-cellular space, and a surrounding capillary network. Each cell is further compartmentalized into cytosol and mitochondria. Inter-compartment interaction is accounted in the form of passive and carrier-mediated transport. Our model was validated against experimental data reported by Crumrine and LaManna, who studied the effect of ischemia and its recovery on various intra-cellular tissue substrates under standard diet conditions. The effect of ketone bodies on brain metabolism was also examined under ischemic conditions following cardiac resuscitation through our model simulations. The influence of ketone bodies on lactate dynamics on mammalian brain following ischemia is studied incorporating experimental data.

  7. Characterization and distribution of receptors for the atrial natriuretic peptides in mammalian brain

    International Nuclear Information System (INIS)

    Quirion, R.; Dalpe, M.; Dam, T.V.

    1986-01-01

    Both rat 125 I-labeled atrial natriuretic polypeptide [ 125 I-ANP or atrial natriuretic factor fragment ANF-(99-126)] and human 125 I-α-ANP or human ANF-(99-126)] bind with high specificity and affinity to an apparent single class of sites in guinea pig brain. Similar results have been reported in peripheral tissues, which indicate that central and peripheral ANP binding sites have fairly similar structural requirements. In vitro receptor autoradiography shows that in the guinea pig brain, 125 I-ANP binding sites are highly concentrated in the external plexiform layer of the olfactory bulb, subfornical organ, various thalamic nuclei, medial geniculate nucleus, and cerebellum. Lower densities are found in the central nucleus of the amygdala, dentate gyrus, hippocampus, and area postrema. Most remaining regions contain much lower densities of sites. In rat brain 125 I-ANP binding sites are differentially distributed, with high densities in the subfornical organ, area postrema, and linings of ventricles but low densities in the thalamus and cerebellum. In monkey brain, 125 I-ANP binding sites are concentrated in the cerebellum. The presence of high densities of 125 I-ANP binding sites in various brain regions strongly suggests the existence of a family of brain-heart peptides, in analogy to the well-known brain-gut peptides. Moreover, the extensive distribution of 125 I-ANP binding sites in mammalian brain suggests that the possible roles of ANP/ANF-like peptides in brain are not restricted to the central regulation of cardiovascular parameters

  8. A quantitative magnetic resonance histology atlas of postnatal rat brain development with regional estimates of growth and variability.

    Science.gov (United States)

    Calabrese, Evan; Badea, Alexandra; Watson, Charles; Johnson, G Allan

    2013-05-01

    There has been growing interest in the role of postnatal brain development in the etiology of several neurologic diseases. The rat has long been recognized as a powerful model system for studying neuropathology and the safety of pharmacologic treatments. However, the complex spatiotemporal changes that occur during rat neurodevelopment remain to be elucidated. This work establishes the first magnetic resonance histology (MRH) atlas of the developing rat brain, with an emphasis on quantitation. The atlas comprises five specimens at each of nine time points, imaged with eight distinct MR contrasts and segmented into 26 developmentally defined brain regions. The atlas was used to establish a timeline of morphometric changes and variability throughout neurodevelopment and represents a quantitative database of rat neurodevelopment for characterizing rat models of human neurologic disease. Published by Elsevier Inc.

  9. Effect of prenatal and postnatal microwave exposures on relative activity of SDH of brain and liver in newborn mice

    International Nuclear Information System (INIS)

    Jiang Huai; Yao Gengdong; Zhou Shiyun

    1987-01-01

    Pregnant mice were irradiated with 3 GHz pulse microwave at 8 mW/cm 2 (SAR 3.0-3.5 mW/g) and part of their offspring were irradiated at 1 mW/cm 2 . The effects on the mitochondria marker enzyme SDH of brain and liver in the newborn mice were observed. SDH was quanlitatively determined by microspectrophotometry. The results show that a decrease in the relative activity of SDH in brain was induced by either prenatal or postnatal microwave exposure (p < 0.01). The greatest decrease in the relative activity of SDH occurred in the offspring exposed both prenatally and postnatally. The similar but less changes in the activity of SDH occurred in liver of these mice. The results indicate that the brain SDH is a sensitive index to observe the subtle metabolic alterations which can not be detected using conventional morphologic teratologic procedures. It is suggested that pregnant women should be protected from high power density microwave exposure

  10. 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.

  11. Hypothyroidism coordinately and transiently affects myelin protein gene expression in most rat brain regions during postnatal development.

    Science.gov (United States)

    Ibarrola, N; Rodríguez-Peña, A

    1997-03-28

    To assess the role of thyroid hormone on myelin gene expression, we have studied the effect of hypothyroidism on the mRNA steady state levels for the major myelin protein genes: myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in different rat brain regions, during the first postnatal month. We found that hypothyroidism reduces the levels of every myelin protein transcript, with striking differences between the different brain regions. Thus, in the more caudal regions, the effect of hypothyroidism was extremely modest, being only evident at the earlier stages of myelination. In contrast, in the striatum and the cerebral cortex the important decrease in the myelin protein transcripts is maintained beyond the first postnatal month. Therefore, thyroid hormone modulates in a synchronous fashion the expression of the myelin genes and the length of its effect depends on the brain region. On the other hand, hyperthyroidism leads to an increase of the major myelin protein transcripts above control values. Finally, lack of thyroid hormone does not change the expression of the oligodendrocyte progenitor-specific gene, the platelet derived growth factor receptor alpha.

  12. Ontogenesis of oxytocin pathways in the mammalian brain: late maturation and psychosocial disorders

    Directory of Open Access Journals (Sweden)

    Valery eGrinevich

    2015-01-01

    Full Text Available Oxytocin (OT, the main neuropeptide of sociality, is expressed in neurons exclusively localized in the hypothalamus. During the last decade, a plethora of neuroendocrine, metabolic, autonomic and behavioral effects of OT has been reported. In the urgency to find treatments to syndromes as invalidating as autism, many clinical trials have been launched in which OT is administered to patients, including adolescents and children. However, the impact of OT on the developing brain and in particular on the embryonic and early postnatal maturation of OT neurons, has been only poorly investigated. In the present review we summarize available (although limited literature on general features of ontogenetic transformation of the OT system, including determination, migration and differentiation of OT neurons. Next, we discuss trajectories of OT receptors (OTR in perinatal period. Furthermore, we provide evidence that early alterations, from birth, in the central OT system lead to severe neurodevelopmental diseases such as feeding deficit in infancy and severe defects in social behavior in adulthood, as described in Prader-Willi syndrome. Our review intends to propose a hypothesis about developmental dynamics of central OT pathways, which are essential for survival right after birth and for the acquisition of social skills later on. A better understanding of the embryonic and early postnatal maturation of the OT system may lead to better OT-based treatments in Prader-Willi syndrome and autism.

  13. Extended postnatal brain development in the longest-lived rodent: prolonged maintenance of neotenous traits in the naked mole-rat brain

    Directory of Open Access Journals (Sweden)

    Miranda E. Orr

    2016-11-01

    Full Text Available The naked mole-rat (NMR is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to three years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At four months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until nine months of age in NMRs, and synaptic protein expression continues to change throughout the first three years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through six weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short

  14. Extended Postnatal Brain Development in the Longest-Lived Rodent: Prolonged Maintenance of Neotenous Traits in the Naked Mole-Rat Brain.

    Science.gov (United States)

    Orr, Miranda E; Garbarino, Valentina R; Salinas, Angelica; Buffenstein, Rochelle

    2016-01-01

    The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan >31 years. Intriguingly, fully-grown naked mole-rats (NMRs) exhibit many traits typical of neonatal rodents. However, little is known about NMR growth and maturation, and we question whether sustained neotenous features when compared to mice, reflect an extended developmental period, commensurate with their exceptionally long life. We tracked development from birth to 3 years of age in the slowest maturing organ, the brain, by measuring mass, neural stem cell proliferation, axonal, and dendritic maturation, synaptogenesis and myelination. NMR brain maturation was compared to data from similar sized rodents, mice, and to that of long-lived mammals, humans, and non-human primates. We found that at birth, NMR brains are significantly more developed than mice, and rather are more similar to those of newborn primates, with clearly laminated hippocampi and myelinated white matter tracts. Despite this more mature brain at birth than mice, postnatal NMR brain maturation occurs at a far slower rate than mice, taking four-times longer than required for mice to fully complete brain development. At 4 months of age, NMR brains reach 90% of adult size with stable neuronal cytostructural protein expression whereas myelin protein expression does not plateau until 9 months of age in NMRs, and synaptic protein expression continues to change throughout the first 3 years of life. Intriguingly, NMR axonal composition is more similar to humans than mice whereby NMRs maintain expression of three-repeat (3R) tau even after brain growth is complete; mice experience an abrupt downregulation of 3R tau by postnatal day 8 which continues to diminish through 6 weeks of age. We have identified key ages in NMR cerebral development and suggest that the long-lived NMR may provide neurobiologists an exceptional model to study brain developmental processes that are compressed in common short-lived laboratory animal models.

  15. Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain.

    Science.gov (United States)

    Inta, Ioana; Vogt, Miriam A; Vogel, Anne S; Bettendorf, Markus; Gass, Peter; Inta, Dragos

    2016-10-01

    NMDA receptor (NMDAR) antagonists induce in perinatal rodent cortical apoptosis and protracted schizophrenia-like alterations ameliorated by antipsychotic treatment. The broad-spectrum antibiotic minocycline elicits antipsychotic and neuroprotective effects. Here we tested, if minocycline protects also against apoptosis triggered by the NMDAR antagonist MK-801 at postnatal day 7. Surprisingly, minocycline induced widespread cortical apoptosis and exacerbated MK-801-triggered cell death. In some areas such as the subiculum, the pro-apoptotic effect of minocycline was even more pronounced than that elicited by MK-801. These data reveal among antipsychotics unique pro-apoptotic properties of minocycline, raising concerns regarding consequences for brain development and the use in children.

  16. Pharmacological and biochemical properties of the benzodiazepine-GABA receptor in codfish brain in comparison with mammalian brain

    International Nuclear Information System (INIS)

    Deng, L.

    1989-01-01

    The GABA receptor of codfish brain is encoded by an ancestral gene of the mammalian GABA receptor based on phylogenetic studies. The mammalian GABA receptor consists of at least two subunits (β and α) which could be photoaffinity labeled by the GABA agonist [ 3 H]muscimol (57 kDa) and the benzodiazepine (BZ) agonist [ 3 H]flunitrazepam (52 kDa), respectively. In contrast, electrophoresis of codfish GABA receptor photoaffinity labeled by the same ligands showed a single radioactive peak on sodium dodecyl surface polyarcylamide gel, giving rise to a relative molecular weight of 56-57 kDa equivalent to the β subunit of 57 kDa in mammals. The homogeneity of purified receptor using benzodiazepine (Ro 7-1986/1) affinity chromatography was further verified by two-dimensional gel electrophoresis based on isoelectric point and molecular weight, in addition to a single band on a silver stained gel and specific activity. The receptor density and affinity constant for [ 3 H]muscimol and [ 3 H]flunitrazepam are comparable to those in bovine, rate, and human brain

  17. Nimodipine accelerates the postnatal development of parvalbumin and S-100β immunoreactivity in the rat brain

    NARCIS (Netherlands)

    Buwalda, Bauke; Naber, Riet; Nyakas, Csaba; Luiten, Paul G.M.

    1994-01-01

    The effects of chronic maternal perinatal nimodipine treatment on the immunocytochemical distribution of the Ca2+-binding proteins parvalbumin (PV) and S-100β in neocortex and hippocampus were studied at the age of postnatal day (PD) 5, 7, 10, 14 and 20. The Ca2+ antagonist nimodipine (1000 ppm BAY

  18. Detachment of Chain-Forming Neuroblasts by Fyn-Mediated Control of cell-cell Adhesion in the Postnatal Brain.

    Science.gov (United States)

    Fujikake, Kazuma; Sawada, Masato; Hikita, Takao; Seto, Yayoi; Kaneko, Naoko; Herranz-Pérez, Vicente; Dohi, Natsuki; Homma, Natsumi; Osaga, Satoshi; Yanagawa, Yuchio; Akaike, Toshihiro; García-Verdugo, Jose Manuel; Hattori, Mitsuharu; Sobue, Kazuya; Sawamoto, Kazunobu

    2018-05-09

    In the rodent olfactory system, neuroblasts produced in the ventricular-subventricular zone of the postnatal brain migrate tangentially in chain-like cell aggregates toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After reaching the OB, the chains are dissociated and the neuroblasts migrate individually and radially toward their final destination. The cellular and molecular mechanisms controlling cell-cell adhesion during this detachment remain unclear. Here we report that Fyn, a nonreceptor tyrosine kinase, regulates the detachment of neuroblasts from chains in the male and female mouse OB. By performing chemical screening and in vivo loss-of-function and gain-of-function experiments, we found that Fyn promotes somal disengagement from the chains and is involved in neuronal migration from the RMS into the granule cell layer of the OB. Fyn knockdown or Dab1 (disabled-1) deficiency caused p120-catenin to accumulate and adherens junction-like structures to be sustained at the contact sites between neuroblasts. Moreover, a Fyn and N-cadherin double-knockdown experiment indicated that Fyn regulates the N-cadherin-mediated cell adhesion between neuroblasts. These results suggest that the Fyn-mediated control of cell-cell adhesion is critical for the detachment of chain-forming neuroblasts in the postnatal OB. SIGNIFICANCE STATEMENT In the postnatal brain, newly born neurons (neuroblasts) migrate in chain-like cell aggregates toward their destination, where they are dissociated into individual cells and mature. The cellular and molecular mechanisms controlling the detachment of neuroblasts from chains are not understood. Here we show that Fyn, a nonreceptor tyrosine kinase, promotes the somal detachment of neuroblasts from chains, and that this regulation is critical for the efficient migration of neuroblasts to their destination. We further show that Fyn and Dab1 (disabled-1) decrease the cell-cell adhesion between chain-forming neuroblasts

  19. How does a specific learning and memory system in the mammalian brain gain control of behavior?

    Science.gov (United States)

    McDonald, Robert J; Hong, Nancy S

    2013-11-01

    This review addresses a fundamental, yet poorly understood set of issues in systems neuroscience. The issues revolve around conceptualizations of the organization of learning and memory in the mammalian brain. One intriguing, and somewhat popular, conceptualization is the idea that there are multiple learning and memory systems in the mammalian brain and they interact in different ways to influence and/or control behavior. This approach has generated interesting empirical and theoretical work supporting this view. One issue that needs to be addressed is how these systems influence or gain control of voluntary behavior. To address this issue, we clearly specify what we mean by a learning and memory system. We then review two types of processes that might influence which memory system gains control of behavior. One set of processes are external factors that can affect which system controls behavior in a given situation including task parameters like the kind of information available to the subject, types of training experience, and amount of training. The second set of processes are brain mechanisms that might influence what memory system controls behavior in a given situation including executive functions mediated by the prefrontal cortex; switching mechanisms mediated by ascending neurotransmitter systems, the unique role of the hippocampus during learning. The issue of trait differences in control of different learning and memory systems will also be considered in which trait differences in learning and memory function are thought to potentially emerge from differences in level of prefrontal influence, differences in plasticity processes, differences in ascending neurotransmitter control, differential access to effector systems like motivational and motor systems. Finally, we present scenarios in which different mechanisms might interact. This review was conceived to become a jumping off point for new work directed at understanding these issues. The outcome of

  20. Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.

    Science.gov (United States)

    Yuan, Zhi-Xin; Rapoport, Stanley I

    2015-10-01

    Transient postnatal exposure of rodents to the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine alters behavior and brain 5-HT neurotransmission during adulthood, and also reduces brain arachidonic (ARA) metabolic consumption and protein level of the ARA metabolizing enzyme, cytochrome P4504A (CYP4A). Brain 20-hydroxyeicosatetraenoic acid (20-HETE), converted by CYP4A from ARA, will be reduced in adult mice treated transiently and postnatally with fluoxetine. Male mice pups were injected i.p. daily with fluoxetine (10mg/kg) or saline during P4-P21. At P90 their brain was high-energy microwaved and analyzed for 20-HETE and six other ARA metabolites by enzyme immunoassay. Postnatal fluoxetine vs. saline significantly decreased brain concentrations of 20-HETE (-70.3%) and 15-epi-lipoxin A4 (-60%) in adult mice, but did not change other eicosanoid concentrations. Behavioral changes in adult mice treated postnatally with fluoxetine may be related to reduced brain ARA metabolism involving CYP4A and 20-HETE formation. Published by Elsevier Ltd.

  1. Neocortical Transplants in the Mammalian Brain Lack a Blood-Brain Barrier to Macromolecules

    Science.gov (United States)

    Rosenstein, Jeffrey M.

    1987-02-01

    In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function.

  2. Complement mRNA in the mammalian brain: responses to Alzheimer's disease and experimental brain lesioning.

    Science.gov (United States)

    Johnson, S A; Lampert-Etchells, M; Pasinetti, G M; Rozovsky, I; Finch, C E

    1992-01-01

    This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.

  3. Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures

    Science.gov (United States)

    Zhang, Feng; Gradinaru, Viviana; Adamantidis, Antoine R; Durand, Remy; Airan, Raag D; de Lecea, Luis; Deisseroth, Karl

    2015-01-01

    Elucidation of the neural substrates underlying complex animal behaviors depends on precise activity control tools, as well as compatible readout methods. Recent developments in optogenetics have addressed this need, opening up new possibilities for systems neuroscience. Interrogation of even deep neural circuits can be conducted by directly probing the necessity and sufficiency of defined circuit elements with millisecond-scale, cell type-specific optical perturbations, coupled with suitable readouts such as electrophysiology, optical circuit dynamics measures and freely moving behavior in mammals. Here we collect in detail our strategies for delivering microbial opsin genes to deep mammalian brain structures in vivo, along with protocols for integrating the resulting optical control with compatible readouts (electrophysiological, optical and behavioral). The procedures described here, from initial virus preparation to systems-level functional readout, can be completed within 4–5 weeks. Together, these methods may help in providing circuit-level insight into the dynamics underlying complex mammalian behaviors in health and disease. PMID:20203662

  4. A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain.

    Science.gov (United States)

    Nichols, Charles D; Sanders-Bush, Elaine

    2002-05-01

    Hallucinogenic drugs such as lysergic acid diethylamide (LSD) have profound effects on humans including hallucinations and detachment from reality. These remarkable behavioral effects have many similarities to the debilitating symptoms of neuropsychiatric disorders such as schizophrenia. The effects of hallucinogens are thought to be mediated by serotonin receptor activation; however, how these drugs elicit the unusual behavioral effects remains largely a mystery, despite much research. We have undertaken the first comprehensive analysis of gene expression influenced by acute LSD administration in the mammalian brain. These studies represent a novel approach to elucidate the mechanism of action of this class of drugs. We have identified a number of genes that are predicted to be involved in the processes of synaptic plasticity, glutamatergic signaling and cytoskeletal architecture. Understanding these molecular events will lead to new insights into the etiology of disorders whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs, and also may ultimately result in new therapies.

  5. Nonlinear transfer function encodes synchronization in a neural network from the mammalian brain.

    Science.gov (United States)

    Menendez de la Prida, L; Sanchez-Andres, J V

    1999-09-01

    Synchronization is one of the mechanisms by which the brain encodes information. The observed synchronization of neuronal activity has, however, several levels of fluctuations, which presumably regulate local features of specific areas. This means that biological neural networks should have an intrinsic mechanism able to synchronize the neuronal activity but also to preserve the firing capability of individual cells. Here, we investigate the input-output relationship of a biological neural network from developing mammalian brain, i.e., the hippocampus. We show that the probability of occurrence of synchronous output activity (which consists in stereotyped population bursts recorded throughout the hippocampus) is encoded by a sigmoidal transfer function of the input frequency. Under this scope, low-frequency inputs will not produce any coherent output while high-frequency inputs will determine a synchronous pattern of output activity (population bursts). We analyze the effect of the network size (N) on the parameters of the transfer function (threshold and slope). We found that sigmoidal functions realistically simulate the synchronous output activity of hippocampal neural networks. This outcome is particularly important in the application of results from neural network models to neurobiology.

  6. Beneficial effect of feeding a ketogenic diet to mothers on brain development in their progeny with a murine model of pyruvate dehydrogenase complex deficiency

    Directory of Open Access Journals (Sweden)

    Lioudmila Pliss

    2016-06-01

    Conclusion: The findings provide for the first time experimental support for beneficial effects of a ketogenic diet during the prenatal and early postnatal periods on the brain development of PDC-deficient mammalian progeny.

  7. Recombinant Adeno-Associated Virus-Mediated microRNA Delivery into the Postnatal Mouse Brain Reveals a Role for miR-134 in Dendritogenesis in Vivo

    DEFF Research Database (Denmark)

    Christensen, Mette; Larsen, Lars A; Kauppinen, Sakari

    2010-01-01

    delivery of microRNAs in vivo by use of recombinant adeno-associated virus (rAAV). rAAV-mediated overexpression of miR-134 in neurons of the postnatal mouse brain provided evidence for a negative role of miR-134 in dendritic arborization of cortical layer V pyramidal neurons in vivo, thereby confirming...

  8. Safe and stable noninvasive focal gene delivery to the mammalian brain following focused ultrasound.

    Science.gov (United States)

    Stavarache, Mihaela A; Petersen, Nicholas; Jurgens, Eric M; Milstein, Elizabeth R; Rosenfeld, Zachary B; Ballon, Douglas J; Kaplitt, Michael G

    2018-04-27

    OBJECTIVE Surgical infusion of gene therapy vectors has provided opportunities for biological manipulation of specific brain circuits in both animal models and human patients. Transient focal opening of the blood-brain barrier (BBB) by MR-guided focused ultrasound (MRgFUS) raises the possibility of noninvasive CNS gene therapy to target precise brain regions. However, variable efficiency and short follow-up of studies to date, along with recent suggestions of the potential for immune reactions following MRgFUS BBB disruption, all raise questions regarding the viability of this approach for clinical translation. The objective of the current study was to evaluate the efficiency, safety, and long-term stability of MRgFUS-mediated noninvasive gene therapy in the mammalian brain. METHODS Focused ultrasound under the control of MRI, in combination with microbubbles consisting of albumin-coated gas microspheres, was applied to rat striatum, followed by intravenous infusion of an adeno-associated virus serotype 1/2 (AAV1/2) vector expressing green fluorescent protein (GFP) as a marker. Following recovery, animals were followed from several hours up to 15 months. Immunostaining for GFP quantified transduction efficiency and stability of expression. Quantification of neuronal markers was used to determine histological safety over time, while inflammatory markers were examined for evidence of immune responses. RESULTS Transitory disruption of the BBB by MRgFUS resulted in efficient delivery of the AAV1/2 vector to the targeted rodent striatum, with 50%-75% of striatal neurons transduced on average. GFP transgene expression appeared to be stable over extended periods of time, from 2 weeks to 6 months, with evidence of ongoing stable expression as long as 16 months in a smaller cohort of animals. No evidence of substantial toxicity, tissue injury, or neuronal loss was observed. While transient inflammation from BBB disruption alone was noted for the first few days, consistent

  9. Flow cytometric examination of apoptotic effect on brain tissue in postnatal period created by intrauterine oxcarbazepine and gabapentin exposure.

    Science.gov (United States)

    Erisgin, Z; Tekelioglu, Y

    For epileptics, pregnancy contains the balance between no seizure period and antiepileptic use having the least teratogenicity risk. The purpose is to analyse with flow cytometry the apoptotic effects on postnatal brain tissue caused by prenatal use of second generation antiepileptics oxcarbazepine (OXC) and gabapentin (GBP) having different effect mechanisms. 30 (n = 5 each group) Wistar albino male rats (45-days-old) are used. First 3 groups are exposed to OXC (100 mg/kg/day), GBP (50 mg/kg/day), and saline, respectively on the 1st-5th prenatal days (preimplantation-implantation period) while the second 3 groups are exposed to the same substances on the 6th-15th prenatal days (organogenesis), respectively. After sacrifice, brain tissue samples were made into suspension with mechanic and enzymatic digestion and examined with flow cytometry. While apoptosis rate appeared high in rats exposed to OXC on the 1st-5th (p effect in three treatment groups, while difference was not significant for PSS and GBP groups (p = 0.847 and p = 0.934), apoptosis rate was significantly high for OXC on the 6th-15th days compared to the 1st-5th days (p < 0.001). It is observed that the use of OXC causes neurotoxicity during preimplantation, implantation and, especially, organogenesis period (neurogenesis) whereas GBP does not (Fig. 3, Ref. 32).

  10. Dental Fluorosis and Catalase Immunoreactivity of the Brain Tissues in Rats Exposed to High Fluoride Pre- and Postnatally.

    Science.gov (United States)

    Güner, Şirin; Uyar-Bozkurt, Süheyla; Haznedaroğlu, Eda; Menteş, Ali

    2016-11-01

    This study evaluated dental fluorosis of the incisors and immunoreactivity in the brain tissues of rats given chronic fluoride doses pre- and postnatally. Female rats were given drinking water with 0, 30 or 100 ppm fluoride ad libitum throughout gestation and the nursing period. In addition, 63 male offspring were treated with the same water regimens as the mothers after weaning and were followed for 1, 3 or 5 months. The upper and lower incisors were collected, and all teeth were examined under a stereomicroscope and scored by two blinded examiners using a modified rodent enamel fluorosis index. Cortical, hippocampal and cerebellar brain samples were evaluated morphologically and immunohistochemically. All fluoride-treated pups were born with low body weight (p = 0.001). All animals from the fluoride groups had enamel fluorosis with defects of various degrees. The increase in the dental fluorosis scores in the fluoride treatment groups was significant (p fluoride groups was significantly higher than that in the controls after 1, 3 and 5 months (p toxicity of fluoride.

  11. Modeling Early Postnatal Brain Growth and Development with CT: Changes in the Brain Radiodensity Histogram from Birth to 2 Years.

    Science.gov (United States)

    Cauley, K A; Hu, Y; Och, J; Yorks, P J; Fielden, S W

    2018-04-01

    The majority of brain growth and development occur in the first 2 years of life. This study investigated these changes by analysis of the brain radiodensity histogram of head CT scans from the clinical population, 0-2 years of age. One hundred twenty consecutive head CTs with normal findings meeting the inclusion criteria from children from birth to 2 years were retrospectively identified from 3 different CT scan platforms. Histogram analysis was performed on brain-extracted images, and histogram mean, mode, full width at half maximum, skewness, kurtosis, and SD were correlated with subject age. The effects of scan platform were investigated. Normative curves were fitted by polynomial regression analysis. Average total brain volume was 360 cm 3 at birth, 948 cm 3 at 1 year, and 1072 cm 3 at 2 years. Total brain tissue density showed an 11% increase in mean density at 1 year and 19% at 2 years. Brain radiodensity histogram skewness was positive at birth, declining logarithmically in the first 200 days of life. The histogram kurtosis also decreased in the first 200 days to approach a normal distribution. Direct segmentation of CT images showed that changes in brain radiodensity histogram skewness correlated with, and can be explained by, a relative increase in gray matter volume and an increase in gray and white matter tissue density that occurs during this period of brain maturation. Normative metrics of the brain radiodensity histogram derived from routine clinical head CT images can be used to develop a model of normal brain development. © 2018 by American Journal of Neuroradiology.

  12. Cosplicing network analysis of mammalian brain RNA-Seq data utilizing WGCNA and Mantel correlations

    Directory of Open Access Journals (Sweden)

    Ovidiu Dan Iancu

    2015-05-01

    Full Text Available Across species and tissues and especially in the mammalian brain, production of gene isoforms is widespread. While gene expression coordination has been previously described as a scale-free coexpression network, the properties of transcriptome-wide isoform production coordination have been less studied. Here we evaluate the system-level properties of cosplicing in mouse, macaque and human brain gene expression data using a novel network inference procedure. Genes are represented as vectors/lists of exon counts and distance measures sensitive to exon inclusion rates quantifies differences across samples. For all gene pairs, distance matrices are correlated across samples, resulting in cosplicing or co-transcriptional network matrices. We show that networks including cosplicing information are scale-free and distinct from coexpression. In the networks capturing cosplicing we find a set of novel hubs with unique characteristics distinguishing them from coexpression hubs: heavy representation in neurobiological functional pathways, strong overlap with markers of neurons and neuroglia, long coding lengths, and high number of both exons and annotated transcripts. Further, the cosplicing hubs are enriched in genes associated with autism spectrum disorders. Cosplicing hub homologs across eukaryotes show dramatically increasing intronic lengths but stable coding region lengths. Shared transcription factor binding sites increase coexpression but not cosplicing; the reverse is true for splicing-factor binding sites. Genes with protein-protein interactions have strong coexpression and cosplicing. Additional factors affecting the networks include shared microRNA binding sites, spatial colocalization within the striatum, and sharing a chromosomal folding domain. Cosplicing network patterns remain relatively stable across species.

  13. Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

    OpenAIRE

    Desouza, Lynette A.; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E.; Kottmann, Andreas H.; Tole, Shubha; Vaidya, Vidita A.

    2011-01-01

    Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and...

  14. Early postnatal development of rat brain is accompanied by generation of lipofuscin-like pigments

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, J.; Ivica, J.; Kagan, Dmytro; Svoboda, Petr

    2011-01-01

    Roč. 347, 1-2 (2011), s. 157-162 ISSN 0300-8177 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) IAA500110606 Institutional research plan: CEZ:AV0Z50110509 Keywords : brain * early development * lipofuscin-like pigments * fluorescence * rat Subject RIV: CE - Biochemistry Impact factor: 2.057, year: 2011

  15. Isolation of murine postnatal brain microglia for phenotypic characterization using magnetic cell separation technology.

    Science.gov (United States)

    Harms, Ashley S; Tansey, Malú G

    2013-01-01

    To shorten the time between brain harvesting and microglia isolation, and characterization, we utilized the MACS(®) neural dissociation kit followed by OctoMACS(®) CD11b magnetic bead isolation technique to positively select for brain microglia expressing the pan-microglial marker CD11b, a key subunit of the membrane attack complex (MAC). This protocol yields a viable and highly pure (>95%) microglial population of approximately 500,000 cells per pup that is amenable for in vitro characterization within hours or days after being harvested from brain tissue. Primary microglia from C57Bl/6 mice were plated for next-day analyses of morphology and cellular markers by immunocytochemistry or for analysis of gene expression under resting or LPS-stimulated conditions. The ease of isolation enables investigators to perform molecular and cellular analyses without having to wait 1-2 weeks to isolate microglia by conventional methods involving mechanical agitation to dislodge these from astrocyte beds.

  16. Developing a de novo targeted knock-in method based on in utero electroporation into the mammalian brain.

    Science.gov (United States)

    Tsunekawa, Yuji; Terhune, Raymond Kunikane; Fujita, Ikumi; Shitamukai, Atsunori; Suetsugu, Taeko; Matsuzaki, Fumio

    2016-09-01

    Genome-editing technology has revolutionized the field of biology. Here, we report a novel de novo gene-targeting method mediated by in utero electroporation into the developing mammalian brain. Electroporation of donor DNA with the CRISPR/Cas9 system vectors successfully leads to knock-in of the donor sequence, such as EGFP, to the target site via the homology-directed repair mechanism. We developed a targeting vector system optimized to prevent anomalous leaky expression of the donor gene from the plasmid, which otherwise often occurs depending on the donor sequence. The knock-in efficiency of the electroporated progenitors reached up to 40% in the early stage and 20% in the late stage of the developing mouse brain. Furthermore, we inserted different fluorescent markers into the target gene in each homologous chromosome, successfully distinguishing homozygous knock-in cells by color. We also applied this de novo gene targeting to the ferret model for the study of complex mammalian brains. Our results demonstrate that this technique is widely applicable for monitoring gene expression, visualizing protein localization, lineage analysis and gene knockout, all at the single-cell level, in developmental tissues. © 2016. Published by The Company of Biologists Ltd.

  17. Effects of an overload of animal protein on the rat: brain DNA alterations and tissue morphological modifications during fetal and post-natal stage.

    Science.gov (United States)

    Greco, A M; Sticchi, R; Boschi, G; Vetrani, A; Salvatore, G

    1985-01-01

    On account of many literature reports about the definite correlation between high animal protein intake and cardiovascular diseases, we have studied the effect of a hyperproteic purified diet (casein 40%, lactalbumin 20%) on fetal and post-natal (not further than 40th day) stage of the rat, when cell subdivision process is faster and therefore damage by nutritional imbalance is certainly more serious. Litters of rats were grouped according to mother's (either hyperproteic or common basic) and rat's (after lactation) diet. Brain DNA and histology of various organs were studied. Hyperproteic diet during fetal stage and lactation would inhibit brain cell subdivision since overall content of brain DNA would be decreased on autoptic finding. Structural changes were also shown in liver, heart, kidney and adrenal cortex, especially when hyperproteic diet was continued even after lactation.

  18. 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

  19. Long-Term Supplementation with Beta Serum Concentrate (BSC, a Complex of Milk Lipids, during Post-Natal Brain Development Improves Memory in Rats

    Directory of Open Access Journals (Sweden)

    Jian Guan

    2015-06-01

    Full Text Available We have previously reported that the supplementation of ganglioside-enriched complex-milk-lipids improves cognitive function and that a phospholipid-enriched complex-milk-lipid prevents age-related cognitive decline in rats. This current study evaluated the effects of post-natal supplementation of ganglioside- and phospholipid-enriched complex-milk-lipids beta serum concentrate (BSC on cognitive function in young rats. The diet of male rats was supplemented with either gels formulated BSC (n = 16 or blank gels (n = 16 from post-natal day 10 to day 70. Memory and anxiety-like behaviors were evaluated using the Morris water maze, dark–light boxes, and elevated plus maze tests. Neuroplasticity and white matter were measured using immunohistochemical staining. The overall performance in seven-day acquisition trials was similar between the groups. Compared with the control group, BSC supplementation reduced the latency to the platform during day one of the acquisition tests. Supplementation improved memory by showing reduced latency and improved path efficiency to the platform quadrant, and smaller initial heading error from the platform zone. Supplemented rats showed an increase in striatal dopamine terminals and hippocampal glutamate receptors. Thus BSC supplementation during post-natal brain development improved learning and memory, independent from anxiety. The moderately enhanced neuroplasticity in dopamine and glutamate may be biological changes underlying the improved cognitive function.

  20. Brain scaling in mammalian evolution as a consequence of concerted and mosaic changes in numbers of neurons and average neuronal cell size

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    Suzana eHerculano-Houzel

    2014-08-01

    Full Text Available Enough species have now been subject to systematic quantitative analysis of the relationship between the morphology and cellular composition of their brain that patterns begin to emerge and shed light on the evolutionary path that led to mammalian brain diversity. Based on an analysis of the shared and clade-specific characteristics of 41 modern mammalian species in 6 clades, and in light of the phylogenetic relationships among them, here we propose that ancestral mammal brains were composed and scaled in their cellular composition like modern afrotherian and glire brains: with an addition of neurons that is accompanied by a decrease in neuronal density and very little modification in glial cell density, implying a significant increase in average neuronal cell size in larger brains, and the allocation of approximately 2 neurons in the cerebral cortex and 8 neurons in the cerebellum for every neuron allocated to the rest of brain. We also propose that in some clades the scaling of different brain structures has diverged away from the common ancestral layout through clade-specific (or clade-defining changes in how average neuronal cell mass relates to numbers of neurons in each structure, and how numbers of neurons are differentially allocated to each structure relative to the number of neurons in the rest of brain. Thus, the evolutionary expansion of mammalian brains has involved both concerted and mosaic patterns of scaling across structures. This is, to our knowledge, the first mechanistic model that explains the generation of brains large and small in mammalian evolution, and it opens up new horizons for seeking the cellular pathways and genes involved in brain evolution.

  1. Zn2+, not Ca2+, is the most effective cation for activation of dolichol kinase of mammalian brain.

    Science.gov (United States)

    Sakakihara, Y; Volpe, J J

    1985-12-15

    The cation specificity of dolichol kinase of mammalian brain and the potential involvement of a Ca2+-calmodulin system in regulation of this enzyme have been studied. Among 10 divalent cations examined, Zn2+ was found to be most effective for the activation of dolichol kinase of rat and calf brain and cultured C-6 glial cells. The activations with Ca2+, Co2+, and Mg2+ were 53%, 32%, and 18% of the full activation with Zn2+, respectively. No combinations of the cations could activate the enzyme as much as Zn2+ alone. A role for a Ca2+-calmodulin system in the regulation of brain dolichol kinase was not supported by our data. First, the concentration of free Ca2+ required for the maximum activation of dolichol kinase was two to three orders of magnitude greater than the concentration required by typical calmodulin-dependent enzymes. Second, neither the depletion of calmodulin from the microsomal fraction nor the addition of exogenous calmodulin caused an alteration in the activation of dolichol kinase by Ca2+ (or Zn2+). Third, antagonists of calmodulin failed to suppress the activation of the enzyme by Ca2+ (or Zn2+). The data raise the possibility that Zn2+ is involved in the regulation of dolichol kinase in brain.

  2. Effects of naltrexone in postnatal rats on the recovery of disturbed brain and lymphatic tissues after X-irradiation or ethylnitrosourea treatment in utero

    International Nuclear Information System (INIS)

    Schmahl, W.G.; Plendl, J.; Reinoehl-Kompa, S.

    1987-01-01

    The role of endogenous opioid systems in preweaning development after intrauterine exposure to X-irradiation or ethylnitrosourea (ENU) was explored in rats using naltrexone, a potent antagonist of beta-endorphin. After daily s.c. injections of 50 mg/kg naltrexone only the prenatally untreated controls had body weights increased by 11% from control level on day 28 (weaning). In the X-irradiated as well as the ENU-treated pups no significant effects of naltrexone on body weight gain were observed. However, brain weight increased in all animals under the influence of naltrexone, irrespective of prenatal treatment or the severity of brain lesions: 9.5% above control values in untreated offspring and 14% after X-irradiation (1 Gy) on gestation day 14. The brain weight of ENU-treated rats (50 mg/kg on gest. day 14) was 13% higher after postnatal naltrexone application than that of their postnatally untreated counterparts. ENU (80 mg/kg) effects on the brain when given on gestation day 18 were ameliorated to 9.2% by naltrexone in the weaning period. Naltrexone significantly increased the thymus weight in controls. Prenatally treated animals also showed an increased thymus weight at weaning, presumably due to compensatory growth. In these cases naltrexone revealed a suppressive effect on the thymus, whereas spleen weight was apparently not influenced by naltrexone treatment. These results provide compelling evidence that endogenous opioid systems play a crucial role not only in normal development, but also in reparative growth events of the brain after prenatal injuries. The thymus, predominantly containing T-lymphocytes, seems to represent another sensitive system which is regulated under the influence of opioids

  3. The evolution of Homo sapiens denisova and Homo sapiens neanderthalensis miRNA targeting genes in the prenatal and postnatal brain.

    Science.gov (United States)

    Gunbin, Konstantin V; Afonnikov, Dmitry A; Kolchanov, Nikolay A; Derevianko, Anatoly P; Rogaev, Eugeny I

    2015-01-01

    As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain. A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development. Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.

  4. Effects of naltrexone in postnatal rats on the recovery of disturbed brain and lymphatic tissues after X-irradiation or ethylnitrosourea treatment in utero

    Energy Technology Data Exchange (ETDEWEB)

    Schmahl, W.G.; Plendl, J.; Reinoehl-Kompa, S.

    1987-01-01

    The role of endogenous opioid systems in preweaning development after intrauterine exposure to X-irradiation or ethylnitrosourea (ENU) was explored in rats using naltrexone, a potent antagonist of beta-endorphin. After daily s.c. injections of 50 mg/kg naltrexone only the prenatally untreated controls had body weights increased by 11% from control level on day 28 (weaning). In the X-irradiated as well as the ENU-treated pups no significant effects of naltrexone on body weight gain were observed. However, brain weight increased in all animals under the influence of naltrexone, irrespective of prenatal treatment or the severity of brain lesions: 9.5% above control values in untreated offspring and 14% after X-irradiation (1 Gy) on gestation day 14. The brain weight of ENU-treated rats (50 mg/kg on gest. day 14) was 13% higher after postnatal naltrexone application than that of their postnatally untreated counterparts. ENU (80 mg/kg) effects on the brain when given on gestation day 18 were ameliorated to 9.2% by naltrexone in the weaning period. Naltrexone significantly increased the thymus weight in controls. Prenatally treated animals also showed an increased thymus weight at weaning, presumably due to compensatory growth. In these cases naltrexone revealed a suppressive effect on the thymus, whereas spleen weight was apparently not influenced by naltrexone treatment. These results provide compelling evidence that endogenous opioid systems play a crucial role not only in normal development, but also in reparative growth events of the brain after prenatal injuries. The thymus, predominantly containing T-lymphocytes, seems to represent another sensitive system which is regulated under the influence of opioids.

  5. Alpha-Hydroxylation of lignoceric and nervonic acids in the brain. Effects of altered thyroid function on postnatal development of the hydroxylase activity.

    Science.gov (United States)

    Murad, S; Strycharz, G D; Kishimoto, Y

    1976-09-10

    Rat brain postnuclear preparations catalyzed the alpha-hydroxylation of nervonic acid with an apparent Km of 3 muM. Evidence has been presented which suggests that nervonic acid in the brain is hydroxylated by the same enzyme system which hydroxylates lignoceric acid. The hydroxylase activity in brains of normal (euthyroid) rats increased rapidly from a low in the period immediately following birth to a maximum at the 23rd day and then declined to a low level characteristic of the mature brain. Neonatal hypothyroidism retarded the development of the activity and shifted its peak to the 39th day after birth. Conversely, neonatal hyperthyroidism accelerated the entire developmental pattern and shifted the peak to the 16th day after birth. The hydroxylase activity in mouse brain was also increased by thyroid hormone administration from the 13th through the 18th day after birth. Unlike normal mice, the low activity in jimpy mice was not affected by this treatment. It is concluded that thyroid hormones play an important role in the control of brain fatty acid alpha-hydroxylation. The stimulation of alpha-hydroxy fatty acid synthesis in response to hyperthyroidism during the early postnatal period may be one of the major effects of thyroid hormones in accelerating myelination of the central nervous system.

  6. Effects of chronic postnatal opioid receptor blockade by naltrexone upon proliferation capacity in the prenatally x-irradiated brain of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Schmahl, W.; Miaskowski, U. (Department of Pathology, Gesellschaft fuer Strahlen-und Umweltforschung mbh Muechen, Neuherberg (West Germany))

    1991-01-01

    We recently reported that in rats prenatally x-irradiated on gestation day 14 with 1 Gy, postnatal chronic application of the opioid antagonist naltrexone (Nx) led to a remarkable growth spurt of the microencephalic brain. In the present study we present histological and autoradiographic results found in the subependymal layer (SEL) of the forebrain lateral ventricles. Nx led to an intermittent augmentation of the mitotic index of the x-irradiated brains within a postnatal observation period of 24 weeks. The most conspicuous finding was transient hyperplasia of the SEL at 4-6 weeks of age which occurred in close proximity to an intact ependymal lining. Districts of the lateral ventricles which were denuded from ependyme and where the rest of the ependymal layer (EL) was dislocated peripherally showed upon Nx treatment a long-lasting SEL hyperplasia with a tendency towards dysplasia. These results revealed that repair proliferation of embryotoxic x-irradiation is normally under strong control by the opioid system. If that system, which exerts a suppressing effect upon glial growth, is blocked by Nx, prominent hyperplastic reactions occur which may be useful for repairing the lesion pattern.

  7. Effects of chronic postnatal opioid receptor blockade by naltrexone upon proliferation capacity in the prenatally x-irradiated brain of the rat

    International Nuclear Information System (INIS)

    Schmahl, W.; Miaskowski, U.

    1991-01-01

    We recently reported that in rats prenatally x-irradiated on gestation day 14 with 1 Gy, postnatal chronic application of the opioid antagonist naltrexone (Nx) led to a remarkable growth spurt of the microencephalic brain. In the present study we present histological and autoradiographic results found in the subependymal layer (SEL) of the forebrain lateral ventricles. Nx led to an intermittent augmentation of the mitotic index of the x-irradiated brains within a postnatal observation period of 24 weeks. The most conspicuous finding was transient hyperplasia of the SEL at 4-6 weeks of age which occurred in close proximity to an intact ependymal lining. Districts of the lateral ventricles which were denuded from ependyme and where the rest of the ependymal layer (EL) was dislocated peripherally showed upon Nx treatment a long-lasting SEL hyperplasia with a tendency towards dysplasia. These results revealed that repair proliferation of embryotoxic x-irradiation is normally under strong control by the opioid system. If that system, which exerts a suppressing effect upon glial growth, is blocked by Nx, prominent hyperplastic reactions occur which may be useful for repairing the lesion pattern

  8. Mammalian development in space

    Science.gov (United States)

    Ronca, April E.

    2003-01-01

    Life on Earth, and thus the reproductive and ontogenetic processes of all extant species and their ancestors, evolved under the constant influence of the Earth's l g gravitational field. These considerations raise important questions about the ability of mammals to reproduce and develop in space. In this chapter, I review the current state of our knowledge of spaceflight effects on developing mammals. Recent studies are revealing the first insights into how the space environment affects critical phases of mammalian reproduction and development, viz., those events surrounding fertilization, embryogenesis, pregnancy, birth, postnatal maturation and parental care. This review emphasizes fetal and early postnatal life, the developmental epochs for which the greatest amounts of mammalian spaceflight data have been amassed. The maternal-offspring system, the coordinated aggregate of mother and young comprising mammalian development, is of primary importance during these early, formative developmental phases. The existing research supports the view that biologically meaningful interactions between mothers and offspring are changed in the weightlessness of space. These changes may, in turn, cloud interpretations of spaceflight effects on developing offspring. Whereas studies of mid-pregnant rats in space have been extraordinarily successful, studies of young rat litters launched at 9 days of postnatal age or earlier, have been encumbered with problems related to the design of in-flight caging and compromised maternal-offspring interactions. Possibilities for mammalian birth in space, an event that has not yet transpired, are considered. In the aggregate, the results indicate a strong need for new studies of mammalian reproduction and development in space. Habitat development and systematic ground-based testing are important prerequisites to future research with young postnatal rodents in space. Together, the findings support the view that the environment within which young

  9. The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice.

    Directory of Open Access Journals (Sweden)

    Xue Gao

    2010-11-01

    Full Text Available FTO (fat mass and obesity associated was identified as an obesity-susceptibility gene by several independent large-scale genome association studies. A cluster of SNPs (single nucleotide polymorphism located in the first intron of FTO was found to be significantly associated with obesity-related traits, such as body mass index, hip circumference, and body weight. FTO encodes a protein with a novel C-terminal α-helical domain and an N-terminal double-strand β-helix domain which is conserved in Fe(II and 2-oxoglutarate-dependent oxygenase family. In vitro, FTO protein can demethylate single-stranded DNA or RNA with a preference for 3-methylthymine or 3-methyluracil. Its physiological substrates and function, however, remain to be defined. Here we report the generation and analysis of mice carrying a conditional deletion allele of Fto. Our results demonstrate that Fto plays an essential role in postnatal growth. The mice lacking Fto completely display immediate postnatal growth retardation with shorter body length, lower body weight, and lower bone mineral density than control mice, but their body compositions are relatively normal. Consistent with the growth retardation, the Fto mutant mice have reduced serum levels of IGF-1. Moreover, despite the ubiquitous expression of Fto, its specific deletion in the nervous system results in similar phenotypes as the whole body deletion, indicating that Fto functions in the central nerve system to regulate postnatal growth.

  10. Expanding the test set: Chemicals with potential to disrupt mammalian brain development

    Science.gov (United States)

    High-throughput test methods including molecular, cellular, and alternative species-based assays that examine critical events of normal brain development are being developed for detection of developmental neurotoxcants. As new assays are developed, a "training set' of chemicals i...

  11. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue

    DEFF Research Database (Denmark)

    Hanrieder, Jørg; Wicher, Grzegorz; Bergquist, Jonas

    2011-01-01

    . Complementary proteomic experiments revealed the identity of these signature proteins that were predominantly expressed in the different glial cell types, including histone H4 for oligodendrocytes and S100-A10 for astrocytes. MALDI imaging MS was performed, and signature masses were employed as molecular...... tracers for prediction of oligodendroglial and astroglial localization in brain tissue. The different cell type specific protein distributions in tissue were validated using immunohistochemistry. ICMS of intact neuroglia is a simple and straightforward approach for characterization and discrimination...

  12. Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

    Directory of Open Access Journals (Sweden)

    Laurent Kappeler

    2008-10-01

    Full Text Available Mutations that decrease insulin-like growth factor (IGF and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.

  13. Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain.

    Directory of Open Access Journals (Sweden)

    Qiwen Hu

    2017-06-01

    Full Text Available A compelling body of literature, based on next generation chromatin immunoprecipitation and RNA sequencing of reward brain regions indicates that the regulation of the epigenetic landscape likely underlies chronic drug abuse and addiction. It is now critical to develop highly innovative computational strategies to reveal the relevant regulatory transcriptional mechanisms that may underlie neuropsychiatric disease. We have analyzed chromatin regulation of alternative splicing, which is implicated in cocaine exposure in mice. Recent literature has described chromatin-regulated alternative splicing, suggesting a novel function for drug-induced neuroepigenetic remodeling. However, the extent of the genome-wide association between particular histone modifications and alternative splicing remains unexplored. To address this, we have developed novel computational approaches to model the association between alternative splicing and histone posttranslational modifications in the nucleus accumbens (NAc, a brain reward region. Using classical statistical methods and machine learning to combine ChIP-Seq and RNA-Seq data, we found that specific histone modifications are strongly associated with various aspects of differential splicing. H3K36me3 and H3K4me1 have the strongest association with splicing indicating they play a significant role in alternative splicing in brain reward tissue.

  14. Mercuric chloride-induced alterations of levels of noradrenaline, dopamine, serotonin and acetylcholine esterase activity in different regions of rat brain during postnatal development

    Energy Technology Data Exchange (ETDEWEB)

    Lakshmana, M.K. (Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India)); Desiraju, T. (Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India)); Raju, T.R. (Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore (India))

    1993-07-01

    Wistar rats were fed mercuric chloride, 4 mg/kg body weight per day chronically from postnatal day 2 to 60 by gastric intubation. Mercury consumption was then discontinued until 170 days to allow time for recovery. Since mercury caused reduction in body weight, an underweight group was also included besides the normal saline group. Levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and the activity of acetylcholine esterase (AChE) were assayed in various brain regions in different age groups. By 60 days of age, the mercury group showed elevations of NA levels in olfactory bulb (OB), visual cortex (VC) and brain stem (BS) but not in striatumaccumbens (SA) and hippocampus (HI). DA levels were also increased in OB, HI, VC and BS but not in SA. AChE activity was decreased in the mercury group only in HI and VC at 20 days of age. The Mercury group showed no behavioural abnormality outwardly; however, operant conditioning relevated a dificiency in performance. Nevertheless, all these changes disappeared after discontinuation of mercury intake. Thus the changes occurring in the brain at this level of oral mercuric chloride intake seem to reflect adaptive neural mechanisms rather than pathological damage. (orig.)

  15. Direct Signaling from Astrocytes to Neurons in Cultures of Mammalian Brain Cells

    Science.gov (United States)

    Nedergaard, Maiken

    1994-03-01

    Although astrocytes have been considered to be supportive, rather than transmissive, in the adult nervous system, recent studies have challenged this assumption by demonstrating that astrocytes possess functional neurotransmitter receptors. Astrocytes are now shown to directly modulate the free cytosolic calcium, and hence transmission characteristics, of neighboring neurons. When a focal electric field potential was applied to single astrocytes in mixed cultures of rat forebrain astrocytes and neurons, a prompt elevation of calcium occurred in the target cell. This in turn triggered a wave of calcium increase, which propagated from astrocyte to astrocyte. Neurons resting on these astrocytes responded with large increases in their concentration of cytosolic calcium. The gap junction blocker octanol attenuated the neuronal response, which suggests that the astrocytic-neuronal signaling is mediated through intercellular connections rather than synaptically. This neuronal response to local astrocytic stimulation may mediate local intercellular communication within the brain.

  16. HZE particle effects in the mammalian brain: relevance to manned space flight

    International Nuclear Information System (INIS)

    Kraft, L.M.; D'Amelio, F.E.; Benton, E.V.

    1980-01-01

    The brain of rodents has been studied following high LET neon particle irradiation with doses ranging from 10 to 1000 rad. The changes observed by light microscopy after 1000 rad irradiation, for example, include acute necrosis of interstitial cells within 36 h of exposure, necrotic neurons, hyperchromatic neuroglia, and axonal degeneration beginning at 3 months postexposure. These changes are compared with those reported following exposure to other radiation modalities. Neuronal necrosis following high LET argon particle irradiation was comparable to that with neon. Low doses (25 rad and below) of iron nuclei resulted in no visible necrotic nerve cells. Acute neuroglial cell loss or damage is discussed as to its possible role in chronic neuronal necrosis and in loss of axonal integrity

  17. Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult Mammalian brain.

    Science.gov (United States)

    Desouza, Lynette A; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E; Kottmann, Andreas H; Tole, Shubha; Vaidya, Vidita A

    2011-05-01

    Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T₃ administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh(+/LacZ) mice. Further, acute T₃ treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T₃ administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone.

  18. Of Mice and Men: Natural Kinds of Emotions in the Mammalian Brain? A Response to Panksepp and Izard.

    Science.gov (United States)

    Barrett, Lisa Feldman; Lindquist, Kristen A; Bliss-Moreau, Eliza; Duncan, Seth; Gendron, Maria; Mize, Jennifer; Brennan, Lauren

    2007-09-01

    For almost 5 decades, the scientific study of emotion has been guided by the assumption that categories such as anger, sadness, and fear cut nature at its joints. Barrett (2006a) provided a comprehensive review of the empirical evidence from the study of emotion in humans and concluded that this assumption has outlived its usefulness. Panksepp and Izard have written lengthy papers (published in this issue) containing complementary but largely nonover lapping criticisms of Barrett (2006a). In our response, we address three of their concerns. First, we discuss the value of correlational versus experimental studies for evaluating the natural-kind model of emotion and refute the claim that the evidence offered in Barrett (2006a) was merely correlational. Second, we take up the issue of whether or not there is evidence for "coherently organized neural circuits for natural kinds of emotions in the mammalian brain and counter the claim that Barrett (2006a) ignored crucial evidence for existence of discrete emotions as natural kinds. Third, we address Panksepp and Izard's misconceptions of an alternative view, the conceptual act model of emotion, that was briefly discussed in Barrett (2006a). Finally, we end the article with some thoughts on how to move the scientific study of emotion beyond the debate over whether or not emotions are natural kinds. © 2007 Association for Psychological Science.

  19. Potential clinical relevance of the 'little brain' on the mammalian heart.

    Science.gov (United States)

    Armour, J A

    2008-02-01

    It is hypothesized that the heart possesses a nervous system intrinsic to it that represents the final relay station for the co-ordination of regional cardiac indices. This 'little brain' on the heart is comprised of spatially distributed sensory (afferent), interconnecting (local circuit) and motor (adrenergic and cholinergic efferent) neurones that communicate with others in intrathoracic extracardiac ganglia, all under the tonic influence of central neuronal command and circulating catecholamines. Neurones residing from the level of the heart to the insular cortex form temporally dependent reflexes that control overlapping, spatially determined cardiac indices. The emergent properties that most of its components display depend primarily on sensory transduction of the cardiovascular milieu. It is further hypothesized that the stochastic nature of such neuronal interactions represents a stabilizing feature that matches cardiac output to normal corporal blood flow demands. Thus, with regard to cardiac disease states, one must consider not only cardiac myocyte dysfunction but also the fact that components within this neuroaxis may interact abnormally to alter myocyte function. This review emphasizes the stochastic behaviour displayed by most peripheral cardiac neurones, which appears to be a consequence of their predominant cardiac chemosensory inputs, as well as their complex functional interconnectivity. Despite our limited understanding of the whole, current data indicate that the emergent properties displayed by most neurones comprising the cardiac neuroaxis will have to be taken into consideration when contemplating the targeting of its individual components if predictable, long-term therapeutic benefits are to accrue.

  20. Transcranial magnetic stimulation of human adult stem cells in the mammalian brain

    Directory of Open Access Journals (Sweden)

    Karlea L Kremer

    2016-03-01

    Full Text Available Introduction: The burden of stroke on the community is growing, and therefore, so is the need for a therapy to overcome the disability following stroke. Cellular-based therapies are being actively investigated at a pre-clinical and clinical level. Studies have reported the beneficial effects of exogenous stem cell implantation, however, these benefits are also associated with limited survival of implanted stem cells. This exploratory study investigated the use of transcranial magnetic stimulation (TMS as a complementary therapy to increase stem cell survival following implantation of human dental pulp stem cells (DPSC in the rodent cortex. Methods: Sprague-Dawley rats were anaesthetised and injected with 6x105 DPSC or control media via an intracranial injection, and then received real TMS (TMS0.2Hz or sham TMS (TMSsham every 2nd day beginning on day 3 post DPSC injection for 2 weeks. Brain sections were analysed for the survival, migration and differentiation characteristics of the implanted cells. Results: In animals treated with DPSC and TMS0.2Hz there were significantly less implanted DPSC and those that survived remained in the original cerebral hemisphere compared to animals that received TMSsham. The surviving implanted DPSC in TMS0.2Hz were also found to express the apoptotic marker Caspase-3. Conclusions: We suggest that TMS at this intensity may cause an increase in glutamate levels, which promotes an unfavourable environment for stem cell implantation, proliferation and differentiation. It should be noted that only one paradigm of TMS was tested as this was conducted as an exploratory study, and further TMS paradigms should be investigated in the future.

  1. Postnatal Development of Brain-Derived Neurotrophic Factor (BDNF) and Tyrosine Protein Kinase B (TrkB) Receptor Immunoreactivity in Multiple Brain Stem Respiratory-Related Nuclei of the Rat

    Science.gov (United States)

    Liu, Qiuli; Wong-Riley, Margaret T.T.

    2013-01-01

    Previously, we found a transient imbalance between suppressed excitation and enhanced inhibition in the respiratory network of the rat around postnatal days (P) 12–13, a critical period when the hypoxic ventilatory response is at its weakest. The mechanism underlying the imbalance is poorly understood. Brain-derived neurotrophic factor (BDNF) and its tyrosine protein kinase B (TrkB) receptors are known to potentiate glutamatergic and attenuate gamma-aminobutyric acid (GABA)ergic neurotransmission, and BDNF is essential for respiratory development. We hypothesized that the excitation-inhibition imbalance during the critical period stemmed from a reduced expression of BDNF and TrkB at that time within respiratory-related nuclei of the brain stem. An in-depth, semiquantitative immunohistochemical study was undertaken in seven respiratory-related brain stem nuclei and one nonrespiratory nucleus in P0–21 rats. The results indicate that the expressions of BDNF and TrkB: 1) in the pre-Bötzinger complex, nucleus ambiguus, commissural and ventrolateral subnuclei of solitary tract nucleus, and retrotrapezoid nucleus/parafacial respiratory group were significantly reduced at P12, but returned to P11 levels by P14; 2) in the lateral paragigantocellular nucleus and parapyramidal region were increased from P0 to P7, but were strikingly reduced at P10 and plateaued thereafter; and 3) in the nonrespiratory cuneate nucleus showed a gentle plateau throughout the first 3 post-natal weeks, with only a slight decline of BDNF expression after P11. Thus, the significant downregulation of both BDNF and TrkB in respiratory-related nuclei during the critical period may form the basis of, or at least contribute to, the inhibitory-excitatory imbalance within the respiratory network during this time. PMID:22678720

  2. Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective Intrauterine Growth Restriction with Concomitant Oligohydramnios.

    Science.gov (United States)

    Ishii, Keisuke; Wada, Seiji; Takano, Mayumi; Nakata, Masahiko; Murakoshi, Takeshi; Sago, Haruhiko

    2018-02-20

    We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin. This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography. Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins. FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option. © 2018 S. Karger AG, Basel.

  3. The effects of short term and chronic exposure to tritiated drinking water on pre- and postnatal brain development

    International Nuclear Information System (INIS)

    Marthens, E. van; Zamenhof, S.

    1982-01-01

    Ingestion of HTO during oocyte maturation and continued during pre-implantation time was found to depress decidual response. At birth these offspring also showed a decrease in brain cell number. When HTO was given during pregnancy only, the offspring at birth showed a similar deficit in brain cell number. Even so, we could not demonstrate a gross deficit in oocyte maturation when HTO was ingested during sexual maturity only; however, when further continued during pregnancy, the measured newborn parameters were most severely affected. In this group, cell-multiplication in the cerebrum was severely decreased, protein synthesis was decreased, and somatic growth was also highly significantly decreased. These experiments indicate that even a short-term exposure to HTO during early pregnancy (pre-implantation) alters normal development to such an extent that it is still observable at birth. During embryonic development, HTO affected the rate of actual cell division and it is apparent that the central nervous system is most vulnerable. If the exposure to HTO is prolonged, the somatic development is also severely affected. (orig./MG)

  4. Plasma Membrane Density of GABA(B)-R1a, GABA(B)-R1b, GABA-R2 and Trimeric G-proteins in the Course of Postnatal Development of Rat Brain Cortex

    Czech Academy of Sciences Publication Activity Database

    Dlouhá, Kateřina; Kagan, Dmytro; Roubalová, Lenka; Ujčíková, Hana; Svoboda, Petr

    2013-01-01

    Roč. 62, č. 5 (2013), s. 547-559 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : GABAB-receptors * postnatal development * rat brain cortex * G-proteins * Na, K- ATPase Subject RIV: CE - Biochemistry Impact factor: 1.487, year: 2013

  5. Role of brain-derived neurotrophic factor in the excitatory-inhibitory imbalance during the critical period of postnatal respiratory development in the rat.

    Science.gov (United States)

    Gao, Xiu-Ping; Zhang, Hanmeng; Wong-Riley, Margaret

    2015-11-01

    The critical period of respiratory development in rats is a narrow window toward the end of the second postnatal week (P12-13), when abrupt neurochemical, electrophysiological, and ventilatory changes occur, when inhibition dominates over excitation, and when the animals' response to hypoxia is the weakest. The goal of this study was to further test our hypothesis that a major mechanism underlying the synaptic imbalance during the critical period is a reduced expression of brain-derived neurotrophic factor (BDNF) and its TrkB receptors. Our aims were to determine (1) that the inhibitory dominance observed in hypoglossal motoneurons during the critical period was also demonstrable in a key respiratory chemosensor, NTSVL; (2) if in vivo application of a TrkB agonist, 7,8-DHF, would prevent, but a TrkB antagonist, ANA-12, would accentuate the synaptic imbalance; and (3) if hypoxia would also heighten the imbalance. Our results indicate that (1) the synaptic imbalance was evident in the NTSVL during the critical period; (2) intraperitoneal injections of 7,8-DHF prevented the synaptic imbalance during the critical period, whereas ANA-12 in vivo accentuated such an imbalance; and (3) acute hypoxia induced the weakest response in both the amplitude and frequency of sEPSCs during the critical period, but it increased the frequency of sIPSCs during the critical period. Thus, our findings are consistent with and strengthen our hypothesis that BDNF and TrkB play a significant role in inducing a synaptic imbalance during the critical period of respiratory development in the rat. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  6. Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system

    OpenAIRE

    Siddiqui, Ruqaiyyah; Edwards-Smallbone, James; Flynn, Robin; Khan, Naveed Ahmed

    2012-01-01

    Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented o...

  7. Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Edwards-Smallbone, James; Flynn, Robin; Khan, Naveed Ahmed

    2012-01-01

    Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented opportunities for the development of novel therapeutics. PMID:21921682

  8. Aggrecan-based extracellular matrix shows unique cortical features and conserved subcortical principles of mammalian brain organization in the Madagascan lesser hedgehog tenrec (Echinops telfairi Martin, 1838).

    Science.gov (United States)

    Morawski, M; Brückner, G; Jäger, C; Seeger, G; Künzle, H; Arendt, T

    2010-02-03

    The Madagascan tenrecs (Afrotheria), an ancient mammalian clade, are characterized by unique brain anatomy. Striking features are an expanded paleocortex but a small and poorly differentiated neocortex devoid of a distinct granular layer IV. To investigate the organization of cortical areas we analyzed extracellular matrix components in perineuronal nets (PNs) using antibodies to aggrecan, lectin staining and hyaluronan-binding protein. Selected subcortical regions were studied to correlate the cortical patterns with features in evolutionary conserved systems. In the neocortex, paleocortex and hippocampus PNs were associated with nonpyramidal neurons. Quantitative analysis in the cerebral cortex revealed area-specific proportions and laminar distribution patterns of neurons ensheathed by PNs. Cortical PNs showed divergent structural phenotypes. Diffuse PNs forming a cotton wool-like perisomatic rim were characteristic of the paleocortex. These PNs were associated with a dense pericellular plexus of calretinin-immunoreactive fibres. Clearly contoured PNs were devoid of a calretinin-positive plexus and predominated in the neocortex and hippocampus. The organization of the extracellular matrix in subcortical nuclei followed the widely distributed mammalian type. We conclude that molecular properties of the aggrecan-based extracellular matrix are conserved during evolution of mammals; however, the matrix scaffold is adapted to specific wiring patterns of cortical and subcortical neuronal networks. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Dissecting Cell-Type Composition and Activity-Dependent Transcriptional State in Mammalian Brains by Massively Parallel Single-Nucleus RNA-Seq.

    Science.gov (United States)

    Hu, Peng; Fabyanic, Emily; Kwon, Deborah Y; Tang, Sheng; Zhou, Zhaolan; Wu, Hao

    2017-12-07

    Massively parallel single-cell RNA sequencing can precisely resolve cellular diversity in a high-throughput manner at low cost, but unbiased isolation of intact single cells from complex tissues such as adult mammalian brains is challenging. Here, we integrate sucrose-gradient-assisted purification of nuclei with droplet microfluidics to develop a highly scalable single-nucleus RNA-seq approach (sNucDrop-seq), which is free of enzymatic dissociation and nucleus sorting. By profiling ∼18,000 nuclei isolated from cortical tissues of adult mice, we demonstrate that sNucDrop-seq not only accurately reveals neuronal and non-neuronal subtype composition with high sensitivity but also enables in-depth analysis of transient transcriptional states driven by neuronal activity, at single-cell resolution, in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Development and aging of the Kisspeptin-GPR54 system in the mammalian brain: what are the impacts on female reproductive function?

    Directory of Open Access Journals (Sweden)

    Isabelle eFranceschini

    2013-03-01

    Full Text Available The prominent role of the G protein coupled receptor GPR54 and its peptide ligand kisspeptin in the progression of puberty has been extensively documented in many mammalian species including humans. Kisspeptins are very potent GnRH secretagogues produced by two main populations of neurons located in two ventral forebrain regions, the preoptic area and the arcuate nucleus (ARC. Within the last two years a substantial amount of data has accumulated concerning the development of these neuronal populations and their timely regulation by central and peripheral factors during fetal, neonatal and peripubertal stages of development. This review focuses on the development of the Kisspeptin-GPR54 system in the brain of female mouse, rat, sheep, monkey and humans. The notion that this system represents a major target through which signals from the environment early in life can re-program reproductive function will also be discussed.

  11. Brain fibronectin expression in prenatally irradiated mice

    International Nuclear Information System (INIS)

    Meznarich, H.K.; McCoy, L.S.; Bale, T.L.; Stiegler, G.L.; Sikov, M.R.

    1993-01-01

    Activation of gene transcription by radiation has been recently demonstrated in vivo. However, little is known on the specificity of these alterations on gene transcription. Prenatal irradiation is a known teratogen that affects the developing mammalian central nervous system (CNS). Altered neuronal migration has been suggested as a mechanism for abnormal development of prenatally irradiated brains. Fibronectin (FN), an extracellular glycoprotein, is essential for neural crest cell migration and neural cell growth. In addition, elevated levels of FN have been found in the extracellular matrix of irradiated lung. To test whether brain FN is affected by radiation, either FN level in insoluble matrix fraction or expression of FN mRNA was examined pre- and postnatally after irradiation. Mice (CD1), at 13 d of gestation (DG), served either as controls or were irradiated with 14 DG, 17 DG, or 5,6, or 14 d postnatal. Brain and liver were collected from offspring and analyzed for either total FN protein levels or relative mRNAs for FN and tubulin. Results of prenatal irradiation on reduction of postnatal brain weight relative to whole are comparable to that reported by others. Insoluble matrix fraction (IMF) per gram of brain, liver, lung, and heart weight was not significantly different either between control and irradiated groups or between postnatal stages, suggesting that radiation did not affect the IMF. However, total amounts of FN in brain IMF at 17 DG were significantly different (p < .02) between normal (1.66 ± 0.80 μg) and irradiated brains (0.58 ± 0.22 μg). FN mRNA was detectable at 13, 14, and 17 DG, but was not detectable at 6 and 14 d postnatal, indicating that FN mRNA is developmentally regulated. 41 refs., 4 figs., 3 tabs

  12. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Directory of Open Access Journals (Sweden)

    Angeliki Lyssimachou

    Full Text Available Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT, which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR and peroxisome proliferator-activated receptor gamma (PPARγ. In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  13. The Mammalian “Obesogen” Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G.; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C. Marisa R.; Teixeira, Catarina; Castro, L. Filipe C.; Santos, Miguel M.

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an “obesogenic” phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound. PMID:26633012

  14. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C Marisa R; Teixeira, Catarina; Castro, L Filipe C; Santos, Miguel M

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  15. Riding the glial monorail: a common mechanism for glial-guided neuronal migration in different regions of the developing mammalian brain.

    Science.gov (United States)

    Hatten, M E

    1990-05-01

    In vitro studies from our laboratory indicate that granule neurons, purified from early postnatal mouse cerebellum, migrate on astroglial fibers by forming a 'migration junction' with the glial fiber along the length of the neuronal soma and extending a motile 'leading process' in the direction of migration. Similar dynamics are seen for hippocampal neurons migrating along hippocampal astroglial fibers in vitro. In heterotypic recombinations of neurons and glia from mouse cerebellum and rat hippocampus, neurons migrate on astroglial processes with a cytology and neuron-glia relationship identical to that of homotypic neuronal migration in vitro. In all four cases, the migrating neuron presents a stereotyped posture, speed and mode of movement, suggesting that glial fibers provide a generic pathway for neuronal migration in developing brain. Studies on the molecular basis of glial-guided migration suggest that astrotactin, a neuronal antigen that functions as a neuron-glia ligand, is likely to play a crucial role in the locomotion of the neuron along glial fibers. The navigation of neurons from glial fibers into cortical layers, in turn, is likely to involve neuron-neuron adhesion ligands.

  16. Imaging grafted cells with [18F]FHBG using an optimized HSV1-TK mammalian expression vector in a brain injury rodent model.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Salabert

    Full Text Available Cell transplantation is an innovative therapeutic approach after brain injury to compensate for tissue damage. To have real-time longitudinal monitoring of intracerebrally grafted cells, we explored the feasibility of a molecular imaging approach using thymidine kinase HSV1-TK gene encoding and [18F]FHBG as a reporter probe to image enzyme expression.A stable neuronal cell line expressing HSV1-TK was developed with an optimised mammalian expression vector to ensure long-term transgene expression. After [18F]FHBG incubation under defined parameters, calibration ranges from 1 X 104 to 3 X 106 Neuro2A-TK cells were analysed by gamma counter or by PET-camera. In parallel, grafting with different quantities of [18F]FHBG prelabelled Neuro2A-TK cells was carried out in a rat brain injury model induced by stereotaxic injection of malonate toxin. Image acquisition of the rats was then performed with PET/CT camera to study the [18F]FHBG signal of transplanted cells in vivo.Under the optimised incubation conditions, [18F]FHBG cell uptake rate was around 2.52%. In-vitro calibration range analysis shows a clear linear correlation between the number of cells and the signal intensity. The PET signal emitted into rat brain correlated well with the number of cells injected and the number of surviving grafted cells was recorded via the in-vitro calibration range. PET/CT acquisitions also allowed validation of the stereotaxic injection procedure. Technique sensitivity was evaluated under 5 X 104 grafted cells in vivo. No [18F]FHBG or [18F]metabolite release was observed showing a stable cell uptake even 2 h post-graft.The development of this kind of approach will allow grafting to be controlled and ensure longitudinal follow-up of cell viability and biodistribution after intracerebral injection.

  17. 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.

  18. Possible contributions of a novel form of synaptic plasticity in Aplysia to reward, memory, and their dysfunctions in mammalian brain.

    Science.gov (United States)

    Hawkins, Robert D

    2013-09-18

    Recent studies in Aplysia have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate- and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in mammals, where it may contribute to reward, memory, and their dysfunctions in several psychiatric disorders. In Aplysia, spontaneous release is enhanced by activation of presynaptic serotonin receptors, but presynaptic D1 dopamine receptors or nicotinic acetylcholine receptors could play a similar role in mammals. Those receptors enhance spontaneous release of glutamate in hippocampus, entorhinal cortex, prefrontal cortex, ventral tegmental area, and nucleus accumbens. In all of those brain areas, glutamate can activate postsynaptic receptors to elevate Ca(2+) and engage mechanisms of early-phase long-term potentiation (LTP), including AMPA receptor insertion, and of late-phase LTP, including protein synthesis and growth. Thus, presynaptic receptors and spontaneous release may contribute to postsynaptic mechanisms of plasticity in brain regions involved in reward and memory, and could play roles in disorders that affect plasticity in those regions, including addiction, Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD).

  19. Influence of prenatal application of angiotensin II and postnatal salt diet on GABAergic and oxytocin system in rat brain steam and cerebellum

    International Nuclear Information System (INIS)

    Jackova, L.; Olexova, L.; Svitok, P.; Senko, T.; Stefanik, P.

    2015-01-01

    Our goal was to determinate how gene expression of GABA transporter 1 (GAT1), glutamate decarboxylase 67 (GAD67) and oxytocin receptor (OTR) is influenced with prenatal exposition to angiotensin II (Ang II) and postnatal salt diet in nucleus tractus solitarii (NTS) and cerebellum in rats. In NTS we observed strong tendency in different reaction of OTR gene expression between Ang II prenatal treatment and control rats after high salt diet. We observed significant influence of sex on GAD67 gene expression in cerebellum. Also, sex in combination with salt diet is significant factor in expression of GAT1 gene in cerebellum. (authors)

  20. Can adult neural stem cells create new brains? Plasticity in the adult mammalian neurogenic niches: realities and expectations in the era of regenerative biology.

    Science.gov (United States)

    Kazanis, Ilias

    2012-02-01

    Since the first experimental reports showing the persistence of neurogenic activity in the adult mammalian brain, this field of neurosciences has expanded significantly. It is now widely accepted that neural stem and precursor cells survive during adulthood and are able to respond to various endogenous and exogenous cues by altering their proliferation and differentiation activity. Nevertheless, the pathway to therapeutic applications still seems to be long. This review attempts to summarize and revisit the available data regarding the plasticity potential of adult neural stem cells and of their normal microenvironment, the neurogenic niche. Recent data have demonstrated that adult neural stem cells retain a high level of pluripotency and that adult neurogenic systems can switch the balance between neurogenesis and gliogenesis and can generate a range of cell types with an efficiency that was not initially expected. Moreover, adult neural stem and precursor cells seem to be able to self-regulate their interaction with the microenvironment and even to contribute to its synthesis, altogether revealing a high level of plasticity potential. The next important step will be to elucidate the factors that limit this plasticity in vivo, and such a restrictive role for the microenvironment is discussed in more details.

  1. Report of the NASA Mammalian Developmental Biology Working Group

    Science.gov (United States)

    Keefe, J. R.

    1985-01-01

    Development is considered to encompass all aspects of the mammalian life span from initial initial germ cell production through the complete life cycle to death of the organism. Thus, gamete production, fertilization, embryogenesis, implantation, fetogenesis, birth, peri- and postnatal maturation, and aging were all considered as stages of a development continuum relevant to problems of Space Biology. Deliberations thus far have been limited to stages of the development cycle from fertilization to early postnatal life. The deliberations are detailed.

  2. [The administration of interleukin-1beta during early postnatal develop ment impairs FGF2, but not TIMP1, mRNA expression in brain structures of adult rats].

    Science.gov (United States)

    Trofimov, A N; Zubareva, O E; Shvarts, A P; Ishchenko, A M; Klimenko, V M

    2014-09-01

    According to the Neurodevelopmental hypothesis, the long-lasting cognitive deficit in schizophrenia and other types of neuropathology may occur by injurious factors, such as hypoxia, traumas, infections that take place during pre- and postnatal development, at least at early stages. These pathological conditions are often associated with the high production of pro-inflammatory cytokine interleukin-1B (IL-1B) by the cells of immune and nervous systems. We investigated the expression of genes involved in the neuroplastic regulation (Fgf2 and Timp2) in medial prefrontal cortex and dorsal and ventral regions of hippocampus of adult rats that were treated with IL-1beta between P15 and P21. The learning impairment in IL-1beta-treated rats is accompanied by lower FGF-2 mRNA levels in medial prefrontal cortex and ventral (not dorsal) hippocampus, but TIMP-1 was not affected. No differences in TIMP-1 and FGF-2 mRNA expressions were observed in untrained IL-1beta-treated when compared to control rats.

  3. Biokinetics of radioiodine (125I) during pre and post-natal development and the interference with the induction of developmental effects in the mouse brain

    International Nuclear Information System (INIS)

    Konermann, G.

    1992-01-01

    On day 13 post-conception, pregnant mice were injected with equal activities of either 125 I-sodium iodide or 5-( 125 I)-iodo-2-deoxyuridine in order to study the biokinetic behaviour in relation to the induction of developmental long-term damage to the brain. Brain weight, cortex diameters and alignment of cortical neurons were more affected by 125 I-IUdR (37-231 kBq.g -1 ) than by 125 I-NaI, consistent with decay sites within the DNA or mainly extranuclear sites, respectively. Dose calculations according to the MIRD scheme gave underestimates of the radiotoxicity, especially for the DNA bound 125 I. This is consistent with pronounced RBE effects derived from in vitro studies. The transfer of these RBE effects to the developing brain is, however, limited by the complex interference between the manifestation and compensation of damage within the prolonged response chains. (author)

  4. Biokinetics of radioiodine ( sup 125 I) during pre and post-natal development and the interference with the induction of developmental effects in the mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Konermann, G. (Freiburg Univ. (Germany). Inst. fuer Biophysik und Strahlenbiologie)

    1992-01-01

    On day 13 post-conception, pregnant mice were injected with equal activities of either {sup 125}I-sodium iodide or 5-({sup 125}I)-iodo-2-deoxyuridine in order to study the biokinetic behaviour in relation to the induction of developmental long-term damage to the brain. Brain weight, cortex diameters and alignment of cortical neurons were more affected by {sup 125}I-IUdR (37-231 kBq.g{sup -1}) than by {sup 125}I-NaI, consistent with decay sites within the DNA or mainly extranuclear sites, respectively. Dose calculations according to the MIRD scheme gave underestimates of the radiotoxicity, especially for the DNA bound {sup 125}I. This is consistent with pronounced RBE effects derived from in vitro studies. The transfer of these RBE effects to the developing brain is, however, limited by the complex interference between the manifestation and compensation of damage within the prolonged response chains. (author).

  5. Neonatal immune activation during early and late postnatal brain development differently influences depression-related behaviors in adolescent and adult C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Jafar Majidi-Zolbanin

    2014-06-01

    Full Text Available Aim: Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions, resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition, previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic double-stranded ribonucleic acid (Poly I: C during different neonatal periods can differently affect depression-related behaviors in adolescent and adult mice. Methods: Male C57BL/6 mice were treated with either saline or Poly I:C (1 mg/kg and 4 mg/kg on postnatal days (PND 3-5 (early neonatal phase or PND 14-16 (late neonatal phase, and then subjected to behavioral tests, including tail suspension test and forced swimming test, during adolescence (PND 35 or 40 and adulthood (PND 85 or 90. Results: The results demonstrated that early neonatal immune activation increases depression-related behaviors in both adolescent and adult mice, but late neonatal immune activation only increases depression in adult mice. In other words, these findings indicated that the nature of the offspring's neuropathology can depend on the severity of the insult, the pup's age at the time of the insult, and offspring age at the time of behavioral testing. Conclusion: These findings suggest that dose and timing of neonatal insult and offspring age may be important factors for evaluating neuropsychiatric disorders in adults who experienced early life infection.

  6. Mammalian sleep

    Science.gov (United States)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  7. Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

    OpenAIRE

    Peluffo, Hugo; Acarin, Laia; Arís, Anna; González, Pau; Villaverde, Antoni; Castellano, Bernardo; González, Berta

    2006-01-01

    Abstract Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD) after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn S...

  8. 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 .

  9. Effect of dietary linoleate/alpha-linolenate balance on the brain lipid composition, reproductive outcome and behavior of rats during their prenatal and postnatal development.

    Science.gov (United States)

    Cheon, S H; Huh, M H; Lee, Y B; Park, J S; Sohn, H S; Chung, C W

    2000-11-01

    The effect of the dietary linoleate (LA)/alpha-linolenate (LNA) balance during development on the brain lipid composition, reproductive outcome and behavior of rats was studied. Female rats were fed on experimental diets during pregnancy and the resulting pups for 16 weeks. The dietary LA/LNA ratios were 1.07 (LA1), 2.64 (LA2), 4.45 (LA3), 7.68 (LA4) and 10.35 (LA5). The relative content of docosahexaenoate (DHA) in the brain of pups tended to increase with decreasing LA/LNA ratio at 0 and 3 weeks, while the level of DHA was maintained constant at 16 weeks regardless of the dietary LA/LNA ratio. The learning ability was measured at 12 weeks of age, and there was no difference among the groups. In an open field test, the exploratory index was significantly lower in the LA1 group than in the LA2 group. The LA1 group had a smaller litter size and lower survival rate than the other groups. We conclude that if the diet contained appropriate amounts and balance of LA and LNA, it was possible for rats to synthesize an appropriate amount of DHA and have normal behavioral activity without DHA supplementation.

  10. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    Science.gov (United States)

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  11. Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

    Science.gov (United States)

    Peluffo, Hugo; Acarin, Laia; Arís, Anna; González, Pau; Villaverde, Antoni; Castellano, Bernardo; González, Berta

    2006-01-01

    Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD) after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after intracortical N-methyl-D-aspartate (NMDA) administration, and daily functional evaluation was performed. Moreover, 3 days after, lesion volume, neuronal degeneration and nitrotyrosine immunoreactivity were evaluated. Results Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved functional outcome and a reduced lesion volume at 3 days post lesion. In secondary degenerative areas, increased neuronal survival as well as decreased numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen. Interestingly, injection of the NLSCt vector carrying the control GFP transgene also displayed a significant neuroprotective effect but less pronounced. Conclusion When the appropriate levels of Cu/Zn SOD are expressed transiently after injury using the non-viral modular protein vector NLSCt a neuroprotective effect is seen. Thus recombinant modular protein vectors may be suitable for in vivo gene therapy, and Cu/Zn SOD should be considered as an interesting therapeutic transgene. PMID:16638118

  12. Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

    Directory of Open Access Journals (Sweden)

    Castellano Bernardo

    2006-04-01

    Full Text Available Abstract Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after intracortical N-methyl-D-aspartate (NMDA administration, and daily functional evaluation was performed. Moreover, 3 days after, lesion volume, neuronal degeneration and nitrotyrosine immunoreactivity were evaluated. Results Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved functional outcome and a reduced lesion volume at 3 days post lesion. In secondary degenerative areas, increased neuronal survival as well as decreased numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen. Interestingly, injection of the NLSCt vector carrying the control GFP transgene also displayed a significant neuroprotective effect but less pronounced. Conclusion When the appropriate levels of Cu/Zn SOD are expressed transiently after injury using the non-viral modular protein vector NLSCt a neuroprotective effect is seen. Thus recombinant modular protein vectors may be suitable for in vivo gene therapy, and Cu/Zn SOD should be considered as an interesting therapeutic transgene.

  13. Mammalian prions

    Science.gov (United States)

    Salamat, Muhammad Khalid; Munoz-Montesino, Carola; Moudjou, Mohammed; Rezaei, Human; Laude, Hubert; Béringue, Vincent; Dron, Michel

    2013-01-01

    Upon prion infection, abnormal prion protein (PrPSc) self-perpetuate by conformational conversion of α-helix-rich PrPC into β sheet enriched form, leading to formation and deposition of PrPSc aggregates in affected brains. However the process remains poorly understood at the molecular level and the regions of PrP critical for conversion are still debated. Minimal amino acid substitutions can impair prion replication at many places in PrP. Conversely, we recently showed that bona fide prions could be generated after introduction of eight and up to 16 additional amino acids in the H2-H3 inter-helix loop of PrP. Prion replication also accommodated the insertions of an octapeptide at different places in the last turns of H2. This reverse genetic approach reveals an unexpected tolerance of prions to substantial sequence changes in the protease-resistant part which is associated with infectivity. It also demonstrates that conversion does not require the presence of a specific sequence in the middle of the H2-H3 area. We discuss the implications of our findings according to different structural models proposed for PrPSc and questioned the postulated existence of an N- or C-terminal prion domain in the protease-resistant region. PMID:23232499

  14. Determination of pharmacological levels of harmane, harmine and harmaline in mammalian brain tissue, cerebrospinal fluid and plasma by high-performance liquid chromatography with fluorimetric detection.

    Science.gov (United States)

    Moncrieff, J

    1989-11-24

    Increased blood aldehyde levels, as occur in alcohol intoxication, could lead to the formation of beta-carbolines such as harmane by condensation with indoleamines. Endogenous beta-carbolines, therefore, should occur in specific brain areas where indoleamine concentrations are high, whilst exogenous beta-carbolines should exhibit an even distribution. The author presents direct and sensitive methods for assaying the beta-carbolines harmane, harmine and harmaline in brain tissue, cerebrospinal fluid and plasma at picogram sample concentrations using reversed-phase high-performance liquid chromatography with fluorimetric detection and minimal sample preparation. Using these assay methods, it was found that the distribution of beta-carbolines from a source exogenous to the brain results in a relatively even distribution within the brain tissue.

  15. 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; ...

  16. Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries.

    Science.gov (United States)

    Zhang, Hua; Zheng, Wenjing; Shen, Yan; Adhikari, Deepak; Ueno, Hiroo; Liu, Kui

    2012-07-31

    It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves in postnatal or adult life, and that the number of oocytes is already fixed in fetal or neonatal ovaries. This assumption, however, has been challenged over the past decade. In this study, we have taken an endogenous genetic approach to this question and generated a multiple fluorescent Rosa26(rbw/+);Ddx4-Cre germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage. Through live cell imaging and de novo folliculogenesis experiments, we show that the Ddx4-expressing cells from postnatal mouse ovaries did not enter mitosis, nor did they contribute to oocytes during de novo folliculogenesis. Our results provide evidence that supports the traditional view that no postnatal follicular renewal occurs in mammals, and no mitotically active Ddx4-expressing female germline progenitors exist in postnatal mouse ovaries.

  17. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

    This section contains summaries of research on mechanisms of lethality and radioinduced changes in mammalian cell properties, new cell systems for the study of the biology of mutation and neoplastic transformation, and comparative properties of ionizing radiations

  18. Taurine Induces Proliferation of Neural Stem Cells and Synapse Development in the Developing Mouse Brain

    Science.gov (United States)

    Shivaraj, Mattu Chetana; Marcy, Guillaume; Low, Guoliang; Ryu, Jae Ryun; Zhao, Xianfeng; Rosales, Francisco J.; Goh, Eyleen L. K.

    2012-01-01

    Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems. PMID:22916184

  19. Activation of postnatal neural stem cells requires nuclear receptor TLX.

    Science.gov (United States)

    Niu, Wenze; Zou, Yuhua; Shen, Chengcheng; Zhang, Chun-Li

    2011-09-28

    Neural stem cells (NSCs) continually produce new neurons in postnatal brains. However, the majority of these cells stay in a nondividing, inactive state. The molecular mechanism that is required for these cells to enter proliferation still remains largely unknown. Here, we show that nuclear receptor TLX (NR2E1) controls the activation status of postnatal NSCs in mice. Lineage tracing indicates that TLX-expressing cells give rise to both activated and inactive postnatal NSCs. Surprisingly, loss of TLX function does not result in spontaneous glial differentiation, but rather leads to a precipitous age-dependent increase of inactive cells with marker expression and radial morphology for NSCs. These inactive cells are mispositioned throughout the granular cell layer of the dentate gyrus during development and can proliferate again after reintroduction of ectopic TLX. RNA-seq analysis of sorted NSCs revealed a TLX-dependent global expression signature, which includes the p53 signaling pathway. TLX regulates p21 expression in a p53-dependent manner, and acute removal of p53 can rescue the proliferation defect of TLX-null NSCs in culture. Together, these findings suggest that TLX acts as an essential regulator that ensures the proliferative ability of postnatal NSCs by controlling their activation through genetic interaction with p53 and other signaling pathways.

  20. Cellular and Chemical Neuroscience of Mammalian Sleep

    OpenAIRE

    Datta, Subimal

    2010-01-01

    Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades, thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and it...

  1. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

    Progress is reported on the following research projects: the effects of N-ethyl-maleimide and hydroxyurea on hamster cells in culture; sensitization of synchronized human cells to x rays by N-ethylmaleimide; sensitization of hypoxic mammalian cells with a sulfhydryl inhibitor; damage interaction due to ionizing and nonionizing radiation in mammalian cells; DNA damage relative to radioinduced cell killing; spurious photolability of DNA labeled with methyl- 14 C-thymidine; radioinduced malignant transformation of cultured mouse cells; a comparison of properties of uv and near uv light relative to cell function and DNA damage; Monte Carlo simulation of DNA damage and repair mechanisms; and radiobiology of fast neutrons

  2. Junctional E-cadherin/p120-catenin Is Correlated with the Absence of Supporting Cells to Hair Cells Conversion in Postnatal Mice Cochleae.

    Science.gov (United States)

    Luo, Wen-Wei; Wang, Xin-Wei; Ma, Rui; Chi, Fang-Lu; Chen, Ping; Cong, Ning; Gu, Yu-Yan; Ren, Dong-Dong; Yang, Juan-Mei

    2018-01-01

    Notch inhibition is known to generate supernumerary hair cells (HCs) at the expense of supporting cells (SCs) in the mammalian inner ear. However, inhibition of Notch activity becomes progressively less effective at inducing SC-to-HC conversion in the postnatal cochlea and balance organs as the animal ages. It has been suggested that the SC-to-HC conversion capacity is inversely correlated with E-cadherin accumulation in postnatal mammalian utricles. However, whether E-cadherin localization is linked to the SC-to-HC conversion capacity in the mammalian inner ear is poorly understood. In the present study, we treated cochleae from postnatal day 0 (P0) with the Notch signaling inhibitor DAPT and observed apparent SC-to-HC conversion along with E-cadherin/p120ctn disruption in the sensory region. In addition, the SC-to-HC conversion capacity and E-cadherin/p120ctn disorganization were robust in the apex but decreased toward the base. We further demonstrated that the ability to regenerate HCs and the disruption of E-cadherin/p120ctn concomitantly decreased with age and ceased at P7, even after extended DAPT treatments. This timing is consistent with E-cadherin/p120ctn accumulation in the postnatal cochleae. These results suggest that the decreasing capacity of SCs to transdifferentiate into HCs correlates with E-cadherin/p120ctn localization in the postnatal cochleae, which might account for the absence of SC-to-HC conversion in the mammalian cochlea.

  3. Building the mammalian testis

    DEFF Research Database (Denmark)

    Svingen, Terje; Koopman, Peter

    2013-01-01

    Development of testes in the mammalian embryo requires the formation and assembly of several cell types that allow these organs to achieve their roles in male reproduction and endocrine regulation. Testis development is unusual in that several cell types such as Sertoli, Leydig, and spermatogonial...

  4. Dedifferentiation and proliferation of mammalian cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Yiqiang Zhang

    2010-09-01

    Full Text Available It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1 cardiomyocyte purification from rat hearts, and 2 genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs, while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+.Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness

  5. The mammalian neocortical pyramidal cell: a new theory on prenatal development

    Directory of Open Access Journals (Sweden)

    Miguel eMarín-Padilla

    2014-01-01

    Full Text Available Mammals’ new cerebral cortex (neocortex and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities using essentially analogous anatomical and neural makeups. The human neocortex starts to develop in the 6-week-old embryo with the establishment of a primordial cortical organization that resembles the primitive cortices of amphibian and reptiles that operated his early motor activities. From the 8th to the 15th week of age, the new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divide its components into those above it (neocortex first lamina and those below it (neocortex subplate elements. From the 16th week of age to birth and postnatally, the new pyramidal neurons continue to elongate functionally their apical dendrite by adding synaptic membrane to incorporate the needed sensory information for operating the animal muscular activities. The new pyramidal neuron’ distinguishing feature is the capacity of elongating anatomically and functionally its apical dendrite (its main receptive surface without losing its original attachment to first lamina or the location of its soma retaining its essential nature. The number of pyramidal cell functional strata established in the motor cortex increases and reflects each mammalian species motor capabilities: the hedgehog needs 2 pyramidal cell functional strata to carry out all its motor activities, the mouse three, cat four, primates 5 and humans 6. The presence of six pyramidal cell functional strata distinguish the human motor cortex from that of others primates. Homo sapiens represent a new evolutionary stage that have transformed his primate brain for operating his unique motor capabilities, such as speaking, writing, painting, sculpturing including thinking as a premotor activity.

  6. Neuroprotective signaling mechanisms in the mammalian brain

    NARCIS (Netherlands)

    Dolga, Amalia Mihaela

    2008-01-01

    Summary Alzheimer’s, Parkinson’s disease and other degenerative disorders are characterized by increased neuronal death. Deregulation of several physiological processes, as a consequence of the neuronal death, occurs especially in the regions of the central nervous system involved in learning and

  7. Postnatal exposure to methyl mercury from fish consumption: a review and new data from the Seychelles Child Development Study.

    Science.gov (United States)

    Myers, Gary J; Thurston, Sally W; Pearson, Alexander T; Davidson, Philip W; Cox, Christopher; Shamlaye, Conrad F; Cernichiari, Elsa; Clarkson, Thomas W

    2009-05-01

    Fish is an important source of nutrition worldwide. Fish contain both the neurotoxin methyl mercury (MeHg) and nutrients important for brain development. The developing brain appears to be most sensitive to MeHg toxicity and mothers who consume fish during pregnancy expose their fetus prenatally. Although brain development is most dramatic during fetal life, it continues for years postnatally and additional exposure can occur when a mother breast feeds or the child consumes fish. This raises the possibility that MeHg might influence brain development after birth and thus adversely affect children's developmental outcomes. We reviewed postnatal MeHg exposure and the associations that have been published to determine the issues associated with it and then carried out a series of analyses involving alternative metrics of postnatal MeHg exposure in the Seychelles Child Development Study (SCDS) Main Cohort. The SCDS is a prospective longitudinal evaluation of prenatal MeHg exposure from fish consumption. The Main Cohort includes 779 subjects on whom recent postnatal exposure data were collected at the 6-, 19-, 29-, 66-, and 107-month evaluations. We examined the association of recent postnatal MeHg exposure with multiple 66- and 107-month outcomes and then used three types of alternative postnatal exposure metrics to examine their association with the children's intelligence quotient (IQ) at 107 months of age. Recent postnatal exposure at 107 months of age was adversely associated with four endpoints, three in females only. One alternative postnatal metric was beneficially associated with 9-year IQ in males only. We found several associations between postnatal MeHg biomarkers and children's developmental endpoints. However, as has been the case with prenatal MeHg exposure in the SCDS Main Cohort study, no consistent pattern of associations emerged to support a causal relationship.

  8. Homogenization of Mammalian Cells.

    Science.gov (United States)

    de Araújo, Mariana E G; Lamberti, Giorgia; Huber, Lukas A

    2015-11-02

    Homogenization is the name given to the methodological steps necessary for releasing organelles and other cellular constituents as a free suspension of intact individual components. Most homogenization procedures used for mammalian cells (e.g., cavitation pump and Dounce homogenizer) rely on mechanical force to break the plasma membrane and may be supplemented with osmotic or temperature alterations to facilitate membrane disruption. In this protocol, we describe a syringe-based homogenization method that does not require specialized equipment, is easy to handle, and gives reproducible results. The method may be adapted for cells that require hypotonic shock before homogenization. We routinely use it as part of our workflow to isolate endocytic organelles from mammalian cells. © 2015 Cold Spring Harbor Laboratory Press.

  9. Rheotaxis guides mammalian sperm

    Science.gov (United States)

    Miki, Kiyoshi; Clapham, David E

    2013-01-01

    Background In sea urchins, spermatozoan motility is altered by chemotactic peptides, giving rise to the assumption that mammalian eggs also emit chemotactic agents that guide spermatozoa through the female reproductive tract to the mature oocyte. Mammalian spermatozoa indeed undergo complex adaptations within the female (the process of capacitation) that are initiated by agents ranging from pH to progesterone, but these factors are not necessarily taxic. Currently, chemotaxis, thermotaxis, and rheotaxis have not been definitively established in mammals. Results Here, we show that positive rheotaxis, the ability of organisms to orient and swim against the flow of surrounding fluid, is a major taxic factor for mouse and human sperm. This flow is generated within 4 hours of sexual stimulation and coitus in female mice; prolactin-triggered oviductal fluid secretion clears the oviduct of debris, lowers viscosity, and generates the stream that guides sperm migration in the oviduct. Rheotaxic movement is demonstrated in capacitated and uncapacitated spermatozoa in low and high viscosity medium. Finally, we show that a unique sperm motion we quantify using the sperm head's rolling rate reflects sperm rotation that generates essential force for positioning the sperm in the stream. Rotation requires CatSper channels, presumably by enabling Ca2+ influx. Conclusions We propose that rheotaxis is a major determinant of sperm guidance over long distances in the mammalian female reproductive tract. Coitus induces fluid flow to guide sperm in the oviduct. Sperm rheotaxis requires rotational motion during CatSper channel-dependent hyperactivated motility. PMID:23453951

  10. Early expression of hypocretin/orexin in the chick embryo brain.

    Directory of Open Access Journals (Sweden)

    Kyle E Godden

    Full Text Available Hypocretin/Orexin (H/O neuropeptides are released by a discrete group of neurons in the vertebrate hypothalamus which play a pivotal role in the maintenance of waking behavior and brain state control. Previous studies have indicated that the H/O neuronal development differs between mammals and fish; H/O peptide-expressing cells are detectable during the earliest stages of brain morphogenesis in fish, but only towards the end of brain morphogenesis (by ∼ 85% of embryonic development in rats. The developmental emergence of H/O neurons has never been previously described in birds. With the goal of determining whether the chick developmental pattern was more similar to that of mammals or of fish, we investigated the emergence of H/O-expressing cells in the brain of chick embryos of different ages using immunohistochemistry. Post-natal chick brains were included in order to compare the spatial distribution of H/O cells with that of other vertebrates. We found that H/O-expressing cells appear to originate from two separate places in the region of the diencephalic proliferative zone. These developing cells express the H/O neuropeptide at a comparatively early age relative to rodents (already visible at 14% of the way through fetal development, thus bearing a closer resemblance to fish. The H/O-expressing cell population proliferates to a large number of cells by a relatively early embryonic age. As previously suggested, the distribution of H/O neurons is intermediate between that of mammalian and non-mammalian vertebrates. This work suggests that, in addition to its roles in developed brains, the H/O peptide may play an important role in the early embryonic development of non-mammalian vertebrates.

  11. 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.

  12. 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

  13. 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

  14. β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus

    OpenAIRE

    O'Dell, Thomas J.; Connor, Steven A.; Guglietta, Ryan; Nguyen, Peter V.

    2015-01-01

    Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The m...

  15. 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.)

  16. Mammalian cell biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1975-01-01

    Studies of the action of N-ethylmaleimide (NEM), as an inhibitor of repair of x radioinduced injuries were extended from synchronous Chinese hamster cells to synchronous human HeLa cells. These studies showed a similar mode of action in both cell types lending support to the notion that conclusions may be extracted from such observations that are of fairly general applicability to mammalian cells. Radiation studies with NEM are being extended to hypoxic cells to inquire if NEM is effective relative to oxygen-independent damage. Observations relative to survival, DNA synthesis, and DNA strand elongation resulting from the addition products to DNA when cells were exposed to near uv in the presence of psoralen were extended. (U.S.)

  17. Revealing tact within postnatal care.

    Science.gov (United States)

    Smythe, Elizabeth; Payne, Deborah; Wilson, Sally; Paddy, Ann; Heard, Kate

    2014-02-01

    In this article, we explore the nature of good postnatal care through a hermeneutic unpacking of the notion of tact, drawing on the philosophical writings of Heidegger, Gadamer, and van Manen. The tactful encounters considered were from a hermeneutic research study within a small, rural birthing center in New Zealand. Insights drawn from the analysis were as follows: the openness of listening, watching and being attuned that builds a positive mode of engagement, recognizing that the distance the woman needs from her nurse/midwife is a call of tact, that tact is underpinned by a spirit of care, within tact there are moods and tact might require firmness, and that all of these factors come together to build trust. We conclude that the attunement of tact requires that the staff member has time to spend with a woman, enough energy to engage, and a spirit of care. Women know that tactful practice builds their confidence and affects their mothering experience. Tact cannot be assumed; it needs to be nurtured and sheltered.

  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. Postnatal depression: a review of recent literature.

    OpenAIRE

    Richards, J P

    1990-01-01

    Depression affects 5-22% of women after childbirth. Some women with postnatal depression will experience a prolonged or relapsing illness that may last until their children enter school. It has adverse effects upon the coping abilities of women, their relationships with their infants, partners and social networks and may adversely affect the educational attainment and behaviour of their children. Since many more women are now active in the workforce, the effects of postnatal depression have o...

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

    Science.gov (United States)

    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.

  1. The interaction between early life epilepsy and autistic-like behavioral consequences: a role for the mammalian target of rapamycin (mTOR pathway.

    Directory of Open Access Journals (Sweden)

    Delia M Talos

    Full Text Available Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1 signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46, phospho-p70S6K (Thr389 and phospho-S6 (Ser235/236, as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308 and phospho-ERK (Thr202/Tyr204. Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures.

  2. Localization of two mammalian cyclin dependent kinases during mammalian meiosis

    NARCIS (Netherlands)

    Ashley, T.; Walpita, D.; de rooij, D. G.

    2001-01-01

    Mammalian meiotic progression, like mitotic cell cycle progression, is regulated by cyclins and cyclin dependent kinases (CDKs). However, the unique requirements of meiosis (homologous synapsis, reciprocal recombination and the dual divisions that segregate first homologues, then sister chromatids)

  3. Mammalian Gut Immunity

    Science.gov (United States)

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  4. Mammalian cell biology

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Progress is reported on studies of the molecular biology and functional changes in cultured mammalian cells following exposure to x radiation, uv radiation, fission neutrons, or various chemical environmental pollutants alone or in combinations. Emphasis was placed on the separate and combined effects of polycyclic aromatic hydrocarbons released during combustion of fossil fuels and ionizing and nonionizing radiations. Sun lamps, which emit a continuous spectrum of near ultraviolet light of 290 nm to 315 nm were used for studies of predictive cell killing due to sunlight. Results showed that exposure to uv light (254 nm) may not be adequate to predict effects produced by sunlight. Data are included from studies on single-strand breaks and repair in DNA of cultured hamster cells exposed to uv or nearultraviolet light. The possible interactions of the polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)-anthracene (DmBA) alone or combined with exposure to x radiation, uv radiation (254 nm) or near ultraviolet simulating sunlight were compared for effects on cell survival

  5. Cryopreservation of mammalian semen.

    Science.gov (United States)

    Curry, Mark R

    2007-01-01

    Mammalian spermatozoa were among the very first cells to be successfully cryopreserved and over the last five decades the use of frozen-thawed semen for artificial insemination has come to play an important role in domestic livestock production. More recently, semen freezing has increasingly been utilized in the establishment of genetic resource banks for endangered species. Semen is collected, most commonly either by use of an artificial vagina or by electroejaculation of an anaesthetized animal, and basic sperm parameters assessed. Semen is extended using a TEST-egg yolk-glycerol diluent, packaged in 0.25-mL plastic straws and slowly cooled to 5 degrees C over a period of 1-2 h. Cooled straws are frozen by suspending within liquid nitrogen vapor above the liquid nitrogen surface before plunging into the liquid phase. Straws are thawed briefly in air before immersing in a 35 degrees C water bath for 15 s, and often are used directly for insemination without any further processing.

  6. Long non-coding RNA expression profiling of mouse testis during postnatal development.

    Directory of Open Access Journals (Sweden)

    Jin Sun

    Full Text Available Mammalian testis development and spermatogenesis play critical roles in male fertility and continuation of a species. Previous research into the molecular mechanisms of testis development and spermatogenesis has largely focused on the role of protein-coding genes and small non-coding RNAs, such as microRNAs and piRNAs. Recently, it has become apparent that large numbers of long (>200 nt non-coding RNAs (lncRNAs are transcribed from mammalian genomes and that lncRNAs perform important regulatory functions in various developmental processes. However, the expression of lncRNAs and their biological functions in post-natal testis development remain unknown. In this study, we employed microarray technology to examine lncRNA expression profiles of neonatal (6-day-old and adult (8-week-old mouse testes. We found that 8,265 lncRNAs were expressed above background levels during post-natal testis development, of which 3,025 were differentially expressed. Candidate lncRNAs were identified for further characterization by an integrated examination of genomic context, gene ontology (GO enrichment of their associated protein-coding genes, promoter analysis for epigenetic modification, and evolutionary conservation of elements. Many lncRNAs overlapped or were adjacent to key transcription factors and other genes involved in spermatogenesis, such as Ovol1, Ovol2, Lhx1, Sox3, Sox9, Plzf, c-Kit, Wt1, Sycp2, Prm1 and Prm2. Most differentially expressed lncRNAs exhibited epigenetic modification marks similar to protein-coding genes and tend to be expressed in a tissue-specific manner. In addition, the majority of differentially expressed lncRNAs harbored evolutionary conserved elements. Taken together, our findings represent the first systematic investigation of lncRNA expression in the mammalian testis and provide a solid foundation for further research into the molecular mechanisms of lncRNAs function in mammalian testis development and spermatogenesis.

  7. Mammalian DNA Repair. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Richard D.

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  8. 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.

  9. Junctional E-cadherin/p120-catenin Is Correlated with the Absence of Supporting Cells to Hair Cells Conversion in Postnatal Mice Cochleae

    Directory of Open Access Journals (Sweden)

    Wen-wei Luo

    2018-02-01

    Full Text Available Notch inhibition is known to generate supernumerary hair cells (HCs at the expense of supporting cells (SCs in the mammalian inner ear. However, inhibition of Notch activity becomes progressively less effective at inducing SC-to-HC conversion in the postnatal cochlea and balance organs as the animal ages. It has been suggested that the SC-to-HC conversion capacity is inversely correlated with E-cadherin accumulation in postnatal mammalian utricles. However, whether E-cadherin localization is linked to the SC-to-HC conversion capacity in the mammalian inner ear is poorly understood. In the present study, we treated cochleae from postnatal day 0 (P0 with the Notch signaling inhibitor DAPT and observed apparent SC-to-HC conversion along with E-cadherin/p120ctn disruption in the sensory region. In addition, the SC-to-HC conversion capacity and E-cadherin/p120ctn disorganization were robust in the apex but decreased toward the base. We further demonstrated that the ability to regenerate HCs and the disruption of E-cadherin/p120ctn concomitantly decreased with age and ceased at P7, even after extended DAPT treatments. This timing is consistent with E-cadherin/p120ctn accumulation in the postnatal cochleae. These results suggest that the decreasing capacity of SCs to transdifferentiate into HCs correlates with E-cadherin/p120ctn localization in the postnatal cochleae, which might account for the absence of SC-to-HC conversion in the mammalian cochlea.

  10. 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.

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

    International Nuclear Information System (INIS)

    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.)

  12. High vulnerability of the developing brain to ionizing radiation

    International Nuclear Information System (INIS)

    Inouye, Minoru

    1991-01-01

    The developing mammalian brain is highly susceptible to environmental teratogenic insults, because of its long-lasting sensitive period extending from the beginning of embryonic organogenesis to the postnatal infantile period, the great vulnerability of undifferentiated neural cells to wide range of environmental agents including ionizing radiation, and the lack of further reproductive capacity of neurons. Disturbances in the production of neurons, and their migration to the cerebral and cerebellar cortices, give rise to malformations of the brain, such as an absent corpus callosum, disorganized cortical architecture, abnormal fissuring of the cerebral and cerebellar hemispheres, heterotopic cortical gray matter, ectopic cerebellar granule cells, microcephaly, etc. The critical developmental stage for the induction of histogenetic disorders of the cerebral cortex in humans is 8 weeks of pregnancy and following some weeks. This corresponds to day 13 of pregnancy for mice and day 15 for rats, i.e., the ventricular cells of fetal telencephalon are most susceptible to radiation-induced cell death in this stage of development. The lowest doses of X- and gamma-radiations which induce detectable biological effects in rats and mice are around 0.02 Gy in increasing acute cell death. Reduced brain weight and abnormal dendritic arborization are induced by 0.25 Gy and more. Histological abnormalities are produced by 0.5 Gy and more, and microcephaly and cerebellar malformations are by 1 Gy and more. (author)

  13. Long-term impact of prematurity on postnatal neurohormonal regulation

    Directory of Open Access Journals (Sweden)

    M. I. Ziborova

    2016-01-01

    Full Text Available This article considers the psychophysiological and neuroendocrine differences characteristic of premature children, which are as a result of long-term perinatal consequences. Particular emphasis is laid on the effects of the hypothalamic-pituitary-adrenocortical stress system, the performance of which is reprogramed during complicated pregnancy, labor, and postnatal period under pain stress due to medical manipulations. Being extremely sensitive to all these exposures, the brain of a premature infant develops during activation of the stress system and takes on a few distinctive properties in addition to independent neuroanatomical distinctions due to premature birth. The altered neurohormonal patterns revealed in very prematurely born children and adolescents involve the regulation of mental processes, behavior, metabolism, and circadian rhythms (sleep-wake regulation, which differ from those in their maturely born peers. These cases allow learning and behavior problems and lower cognitive estimates to be considered in normally developing children born extremely prematurely who have also hormonal dysregulation.

  14. The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus

    DEFF Research Database (Denmark)

    Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong

    2015-01-01

    Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx...

  15. Synchronized Progression of Prestin Expression and Auditory Brainstem Response during Postnatal Development in Rats

    Directory of Open Access Journals (Sweden)

    Jianfeng Hang

    2016-01-01

    Full Text Available Prestin is the motor protein expressed in the cochlear outer hair cells (OHCs of mammalian inner ear. The electromotility of OHCs driven by prestin is responsible for the cochlear amplification which is required for normal hearing in adult animals. Postnatal expression of prestin and activity of OHCs may contribute to the maturation of hearing in rodents. However, the temporal and spatial expression of prestin in cochlea during the development is not well characterized. In the present study, we examined the expression and function of prestin from the OHCs in apical, middle, and basal turns of the cochleae of postnatal rats. Prestin first appeared at postnatal day 6 (P6 for basal turn, P7 in middle turn, and P9 for apical turn of cochlea. The expression level increased progressively over the next few days and by P14 reached the mature level for all three segments. By comparison with the time course of the development of auditory brainstem response for different frequencies, our data reveal that prestin expression synchronized with the hearing development. The present study suggests that the onset time of hearing may require the expression of prestin and is determined by the mature function of OHCs.

  16. Cellular and chemical neuroscience of mammalian sleep.

    Science.gov (United States)

    Datta, Subimal

    2010-05-01

    Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and its cognitive functions. Here I will reflect on our own research contributions to 50 years of extraordinary advances in the neurobiology of slow-wave sleep (SWS) and rapid eye movement (REM) sleep regulation. I conclude this review by suggesting some potential future directions to further our understanding of the neurobiology of sleep. Copyright 2010 Elsevier B.V. All rights reserved.

  17. Prenatal music stimulation facilitates the postnatal functional ...

    Indian Academy of Sciences (India)

    2014-01-27

    Jan 27, 2014 ... In chickens, postnatal short-term exposure to rhythmic musical stimuli ..... Exposure to music has long been associated with enhance cognitive abilities in ... memory performance in the T-maze task (Chaudhury et al. 2010, Sanyal et al. .... children with ADHD and nondisabled children. J. Learn. Disabil.

  18. Radiology of postnatal skeletal development. Pt. 7

    International Nuclear Information System (INIS)

    Ogden, J.A.; Phillips, S.B.

    1983-01-01

    Twenty-four pairs of scapulae from fetal specimens and 35 pairs of scapulae from postnatal cadavers ranging in age from full-term neonates to 14 years, were studied morphologically and roentgenographically. Air-cartilage interfacing was used to demonstrate both the osseous and cartilaginous contours. When the entire chondro-osseous dimensions, rather than just the osseous dimensions, were measured, the scapula had a height-width ratio ranging from 1.36 to 1.52 (average 1.44) during most of fetal development. The exceptions were three stillborns with camptomelic, thanatophoric, and achondrogenic dwarfism in which the ratio averaged 0.6. At no time during fetal development was the glenoid cavity convex; it always had a concave articular surface. However, the osseous subchrondral countour was often flat or slightly convex. In the postnatal period the height-width ratio averaged 1.49. The ratio remained virtually unchanged throughout skeletal growth and maturation. In a patient with unilateral Sprengel's deformity the ratio for the normal side was 1.5, while the abnormal was 1.0. The cartilaginous glenoid cavity was always concave during postnatal development, even in the specimens with major structural deformities, although the subchondral osseous contour was usually flat or convex during the first few years of postnatal development. Ossification of the coracoid process began with the development of a primary center at three to four months. A bipolar physis was present between the primary coracoid center and the primary scapular center until late adolescence. (orig.)

  19. Postnatal depression, oxytocin and maternal sensitivity

    NARCIS (Netherlands)

    Mah, Beth Lynette

    2015-01-01

    Intra nasal oxytocin administered to a population of mothers with a diagnosis of postnatal depression: -lowers their current mood -causes mothers to report that their infants are more difficult but their relationship with them is more positive -increases their protective response towards them in the

  20. Postnatal Loss of Mef2c Results in Dissociation of Effects on Synapse Number and Learning and Memory.

    Science.gov (United States)

    Adachi, Megumi; Lin, Pei-Yi; Pranav, Heena; Monteggia, Lisa M

    2016-07-15

    Myocyte enhancer factor 2 (MEF2) transcription factors play critical roles in diverse cellular processes during central nervous system development. Studies attempting to address the role of MEF2 in brain have largely relied on overexpression of a constitutive MEF2 construct that impairs memory formation or knockdown of MEF2 function that increases spine numbers and enhances memory formation. Genetic deletion of individual MEF2 isoforms in brain during embryogenesis demonstrated that Mef2c loss negatively regulates spine numbers resulting in learning and memory deficits, possibly as a result of its essential role in development. To investigate MEF2C function in brain further, we genetically deleted Mef2c during postnatal development in mice. We characterized these conditional Mef2c knockout mice in an array of behavioral paradigms and examined the impact of postnatal loss of Mef2c on long-term potentiation. We observed increased spine numbers in hippocampus of the conditional Mef2c knockout mice. However, the postnatal loss of Mef2c did not impact learning and memory, long-term potentiation, or social and repetitive behaviors. Our findings demonstrate a critical role for MEF2C in the regulation of spine numbers with a dissociation of learning and memory, synaptic plasticity, and measures of autism-related behaviors in postnatal brain. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Endogenous peripheral neuromodulators of the mammalian taste bud.

    Science.gov (United States)

    Dando, Robin

    2010-10-01

    The sensitivity of the mammalian taste system displays a degree of plasticity based on short-term nutritional requirements. Deficiency in a particular substance may lead to a perceived increase in palatability of this substance, providing an additional drive to redress this nutritional imbalance through modification of intake. This alteration occurs not only in the brain but also, before any higher level processing has occurred, in the taste buds themselves. A brief review of recent advances is offered.

  2. Cell lineage analysis of the mammalian female germline.

    Directory of Open Access Journals (Sweden)

    Yitzhak Reizel

    Full Text Available Fundamental aspects of embryonic and post-natal development, including maintenance of the mammalian female germline, are largely unknown. Here we employ a retrospective, phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites, to study female germline dynamics in mice. Reconstructed cell lineage trees can be used to estimate lineage relationships between different cell types, as well as cell depth (number of cell divisions since the zygote. We show that, in the reconstructed mouse cell lineage trees, oocytes form clusters that are separate from hematopoietic and mesenchymal stem cells, both in young and old mice, indicating that these populations belong to distinct lineages. Furthermore, while cumulus cells sampled from different ovarian follicles are distinctly clustered on the reconstructed trees, oocytes from the left and right ovaries are not, suggesting a mixing of their progenitor pools. We also observed an increase in oocyte depth with mouse age, which can be explained either by depth-guided selection of oocytes for ovulation or by post-natal renewal. Overall, our study sheds light on substantial novel aspects of female germline preservation and development.

  3. In Utero and Postnatal Propylthiouracil-Induced Mild Hypothyroidism Impairs Maternal Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Miski Aghnia Khairinisa

    2018-05-01

    Full Text Available Thyroid hormones (THs play crucial roles in general and brain development. Even if the hypothyroidism is mild, it may alter brain function, resulting in irreversible behavioral alterations. Although various behavioral analyses have been conducted, the effects of propylthiouracil (PTU treatment during in utero and postnatal periods on maternal behavior have not yet been studied. The present study examined in mice whether THs insufficiency during development induce behavioral changes. Pregnant C57BL/6j mice were divided into three groups, and each group was administered different dosages of PTU (0, 5, or 50 ppm in drinking water during in utero and postnatal periods (from gestational day 14 to postnatal day 21. First, locomotor activity and cognitive function were assessed in the offspring at 10 weeks. Next, female offspring were mated with normal mice and they and their offspring were used to assess several aspects of maternal behavior (identifying first pup, returning all pups to nest, time spent nursing, and licking pups. As expected, locomotor and cognitive functions in these mice were disrupted in a PTU dose-dependent manner. On postpartum day 2, dams who had been exposed 50 ppm PTU during in utero and postnatal periods displayed a significantly longer time identifying the first pup and returning all three pups back to the nest, less time nursing, and decreased licking behavior. The decrease in maternal behavior was significantly correlated with a decrease in cognition. These results indicate that insufficiency of THs during in utero and postnatal periods impairs maternal behavior, which may be partly induced by impaired cognitive function.

  4. Beneficial effect of feeding a ketogenic diet to mothers on brain development in their progeny with a murine model of pyruvate dehydrogenase complex deficiency.

    Science.gov (United States)

    Pliss, Lioudmila; Jatania, Urvi; Patel, Mulchand S

    2016-06-01

    Pyruvate dehydrogenase complex (PDC) deficiency is a major inborn error of oxidative metabolism of pyruvate in the mitochondria causing congenital lactic acidosis and primarily structural and functional abnormalities of the central nervous system. To provide an alternate source of acetyl-CoA derived from ketone bodies to the developing brain, a formula high in fat content is widely employed as a treatment. In the present study we investigated efficacy of a high-fat diet given to mothers during pregnancy and lactation on lessening of the impact of PDC deficiency on brain development in PDC-deficient female progeny. A murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene was employed in this study. Maternal consumption of a high-fat diet during pregnancy and lactation had no effect on number of live-birth, body growth, tissue PDC activity levels, as well as the in vitro rates of glucose oxidation and fatty acid biosynthesis by the developing brain of PDC-deficient female offspring during the postnatal age 35 days, as compared to the PDC-deficient progeny born to dams on a chow diet. Interestingly, brain weight was normalized in PDC-deficient progeny of high fat-fed mothers with improvement in impairment in brain structure deficit whereas brain weight was significantly decreased and was associated with greater cerebral structural defects in progeny of chow-fed mothers as compared to control progeny of mothers fed either a chow or high fat diet. The findings provide for the first time experimental support for beneficial effects of a ketogenic diet during the prenatal and early postnatal periods on the brain development of PDC-deficient mammalian progeny.

  5. 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 ...

  6. Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells.

    Science.gov (United States)

    White, Patricia M; Doetzlhofer, Angelika; Lee, Yun Shain; Groves, Andrew K; Segil, Neil

    2006-06-22

    Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.

  7. Classic cadherin expressions balance postnatal neuronal positioning and dendrite dynamics to elaborate the specific cytoarchitecture of the mouse cortical area.

    Science.gov (United States)

    Egusa, Saki F; Inoue, Yukiko U; Asami, Junko; Terakawa, Youhei W; Hoshino, Mikio; Inoue, Takayoshi

    2016-04-01

    A unique feature of the mammalian cerebral cortex is in its tangential parcellation via anatomical and functional differences. However, the cellular and/or molecular machinery involved in cortical arealization remain largely unknown. Here we map expression profiles of classic cadherins in the postnatal mouse barrel field of the primary somatosensory area (S1BF) and generate a novel bacterial artificial chromosome transgenic (BAC-Tg) mouse line selectively illuminating nuclei of cadherin-6 (Cdh6)-expressing layer IV barrel neurons to confirm that tangential cellular assemblage of S1BF is established by postnatal day 5 (P5). When we electroporate the cadherins expressed in both barrel neurons and thalamo-cortical axon (TCA) terminals limited to the postnatal layer IV neurons, S1BF cytoarchitecture is disorganized with excess elongation of dendrites at P7. Upon delivery of dominant negative molecules for all classic cadherins, tangential cellular positioning and biased dendritic arborization of barrel neurons are significantly altered. These results underscore the value of classic cadherin-mediated sorting among neuronal cell bodies, dendrites and TCA terminals in postnatally elaborating the S1BF-specific tangential cytoarchitecture. Additionally, how the "protocortex" machinery affects classic cadherin expression profiles in the process of cortical arealization is examined and discussed. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  8. The shape of mammalian phylogeny

    DEFF Research Database (Denmark)

    Purvis, Andy; Fritz, Susanne A; Rodríguez, Jesús

    2011-01-01

    an assemblage, ecoregion or larger area always tends to be more unbalanced than expected from the phylogeny of species at the next more inclusive spatial scale. We conclude with a verbal model of mammalian macroevolution, which emphasizes the importance to diversification of accessing new regions...

  9. Evolutionary dynamics of mammalian karyotypes

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2012-12-01

    Full Text Available This special volume of Cytogenetic and Genome Research (edited by Roscoe Stanyon, University of Florence and Alexander Graphodatsky, Siberian division of the Russian Academy of Sciences is dedicated to the fascinating long search of the forces behind the evolutionary dynamics of mammalian karyotypes, revealed after the hypotonic miracle of the 1950s....

  10. Technology of mammalian cell encapsulation

    NARCIS (Netherlands)

    Uludag, H; De Vos, P; Tresco, PA

    2000-01-01

    Entrapment of mammalian cells in physical membranes has been practiced since the early 1950s when it was originally introduced as a basic research tool. The method has since been developed based on the promise of its therapeutic usefulness in tissue transplantation. Encapsulation physically isolates

  11. Notching on cancer’s door: Notch signaling in brain tumors

    Directory of Open Access Journals (Sweden)

    Marcin eTeodorczyk

    2015-01-01

    Full Text Available Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4, which are activated by three Delta-like (Dll1/3/4 and two Serrate-like (Jagged1/2 ligands. Further, non-canonical Notch ligands such as EGFL7 have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy.

  12. 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...

  13. Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development.

    Science.gov (United States)

    Bakker, J; Brock, O

    2010-07-01

    A central tenet of contemporary theories on mammalian brain and behavioural sexual differentiation is that an organisational action of testosterone, secreted by the male's testes, controls male-typical aspects of brain and behavioural development, whereas no active perinatal sex hormone signalling is required for female-typical sexual differentiation. Furthermore, the available evidence suggests that many, although not all, of the perinatal organisational actions of testosterone on the development of the male brain result from the cellular effects of oestradiol formed via neural aromatisation of testosterone. However, a default developmental programme for the female brain has been criticised. Indeed, we review new results obtained in aromatase knockout mice indicating that oestradiol actively contributes to the differentiation of female-typical aspects of brain and behavioural sexual differentiation. Furthermore, we propose that male-typical neural and behavioural differentiation occurs prenatally in genetic males under the influence of oestradiol, which is avoided in foetal genetic females by the neuroprotective actions of alpha-fetoprotein, whereas female-typical neural and behavioural differentiation normally occurs postnatally in genetic females under the influence of oestradiol that is presumably produced by the ovaries.

  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. Radiology of postnatal skeletal development. Pt. 7

    Energy Technology Data Exchange (ETDEWEB)

    Ogden, J.A.; Phillips, S.B.

    1983-02-01

    Twenty-four pairs of scapulae from fetal specimens and 35 pairs of scapulae from postnatal cadavers ranging in age from full-term neonates to 14 years, were studied morphologically and roentgenographically. Air-cartilage interfacing was used to demonstrate both the osseous and cartilaginous contours. When the entire chondro-osseous dimensions, rather than just the osseous dimensions, were measured, the scapula had a height-width ratio ranging from 1.36 to 1.52 (average 1.44) during most of fetal development. The exceptions were three stillborns with camptomelic, thanatophoric, and achondrogenic dwarfism in which the ratio averaged 0.6. At no time during fetal development was the glenoid cavity convex; it always had a concave articular surface. However, the osseous subchrondral countour was often flat or slightly convex. In the postnatal period the height-width ratio averaged 1.49. The ratio remained virtually unchanged throughout skeletal growth and maturation. In a patient with unilateral Sprengel's deformity the ratio for the normal side was 1.5, while the abnormal was 1.0. The cartilaginous glenoid cavity was always concave during postnatal development, even in the specimens with major structural deformities, although the subchondral osseous contour was usually flat or convex during the first few years of postnatal development. Ossification of the coracoid process began with the development of a primary center at three to four months. A bipolar physis was present between the primary coracoid center and the primary scapular center until late adolescence.

  16. Factors that affecting mothers’ postnatal comfort

    Directory of Open Access Journals (Sweden)

    Gül Pınar

    2009-01-01

    Full Text Available Aim: The comfort is defined as; “an expected result of a complex conformation of providing peace and help about individual’s needs in a physical, psycho-spiritual, social and environmental entity to overcome the problems”. The aim of this study was to determine the mother’s postnatal comfort and the affecting factors of it.Materials and Methods: This is a sectional and descriptive study. The study was performed on the mothers (n=150 who applied to the delivery service of the Başkent University Ankara Hospital between the date of 30.07.2008 to 31.12.2008. A questionnaire was developed by the investigators to collect data and determine patients’ postnatal comfort scores. Results: The mean age of women was 26.4±3.5 years, the majority of patients had an educational level of high school (68.7% and were multipara (66.0%. It was determined that the mothers had problems and needed help with the fatigue, pain, in standing up, the adverse effect of anesthesia, personal and perineal hygiene that affect their postnatal comfort. The comfort score of the mothers who had spontaneous vaginal birth was higher than those of underwent cesarean delivery (p<0.05.Conclusion: The mothers’ needs and expectations about themselves and their babies were generally supplied by midwifes and the nurses in the postnatal period. Opinion of the mothers about their comfort were influenced to a positive view and the comfort scores increased while the mothers’ satisfaction were augmented (p<0.05.

  17. Prenatal and Postnatal Management of Hydronephrosis

    Science.gov (United States)

    Rao, Pravin K.; Palmer, Jeffrey S.

    2009-01-01

    The majority of pregnant women in the U.S. undergo prenatal ultrasonography and approximately 0.5% of these examinations will detect fetal malformations. Up to one-half of these abnormalities include the genitourinary system and the most common urological finding is hydronephrosis. Some conditions associated with prenatal hydronephrosis portend a poor prognosis, while others can follow a fairly benign course. This review focuses on the definition and prenatal assessment of hydronephrosis, fetal intervention, and postnatal management. PMID:19618087

  18. Thyroid hormone action in postnatal heart development

    Directory of Open Access Journals (Sweden)

    Ming Li

    2014-11-01

    Full Text Available Thyroid hormone is a critical regulator of cardiac growth and development, both in fetal life and postnatally. Here we review the role of thyroid hormone in postnatal cardiac development, given recent insights into its role in stimulating a burst of cardiomyocyte proliferation in the murine heart in preadolescence; a response required to meet the massive increase in circulatory demand predicated by an almost quadrupling of body weight during a period of about 21 days from birth to adolescence. Importantly, thyroid hormone metabolism is altered by chronic diseases, such as heart failure and ischemic heart disease, as well as in very sick children requiring surgery for congenital heart diseases, which results in low T3 syndrome that impairs cardiovascular function and is associated with a poor prognosis. Therapy with T3 or thyroid hormone analogs has been shown to improve cardiac contractility; however, the mechanism is as yet unknown. Given the postnatal cardiomyocyte mitogenic potential of T3, its ability to enhance cardiac function by promoting cardiomyocyte proliferation warrants further consideration.

  19. A mammalian conserved element derived from SINE displays enhancer properties recapitulating Satb2 expression in early-born callosal projection neurons.

    Directory of Open Access Journals (Sweden)

    Kensuke Tashiro

    Full Text Available Short interspersed repetitive elements (SINEs are highly repeated sequences that account for a significant proportion of many eukaryotic genomes and are usually considered "junk DNA". However, we previously discovered that many AmnSINE1 loci are evolutionarily conserved across mammalian genomes, suggesting that they may have acquired significant functions involved in controlling mammalian-specific traits. Notably, we identified the AS021 SINE locus, located 390 kbp upstream of Satb2. Using transgenic mice, we showed that this SINE displays specific enhancer activity in the developing cerebral cortex. The transcription factor Satb2 is expressed by cortical neurons extending axons through the corpus callosum and is a determinant of callosal versus subcortical projection. Mouse mutants reveal a crucial function for Sabt2 in corpus callosum formation. In this study, we compared the enhancer activity of the AS021 locus with Satb2 expression during telencephalic development in the mouse. First, we showed that the AS021 enhancer is specifically activated in early-born Satb2(+ neurons. Second, we demonstrated that the activity of the AS021 enhancer recapitulates the expression of Satb2 at later embryonic and postnatal stages in deep-layer but not superficial-layer neurons, suggesting the possibility that the expression of Satb2 in these two subpopulations of cortical neurons is under genetically distinct transcriptional control. Third, we showed that the AS021 enhancer is activated in neurons projecting through the corpus callosum, as described for Satb2(+ neurons. Notably, AS021 drives specific expression in axons crossing through the ventral (TAG1(-/NPY(+ portion of the corpus callosum, confirming that it is active in a subpopulation of callosal neurons. These data suggest that exaptation of the AS021 SINE locus might be involved in enhancement of Satb2 expression, leading to the establishment of interhemispheric communication via the corpus callosum

  20. Ghrelin: an emerging player in the regulation of reproduction in non-mammalian vertebrates.

    Science.gov (United States)

    Unniappan, Suraj

    2010-07-01

    The endocrine regulation of vertebrate reproduction is achieved by the coordinated actions of multiple endocrine factors mainly produced from the brain, pituitary, and gonads. In addition to these, several other tissues including the fat and gut produce factors that have reproductive effects. Ghrelin is one such gut/brain hormone with species-specific effects in the regulation of mammalian reproduction. Recent studies have shown that ghrelin and ghrelin receptor mRNAs, and protein are expressed in the ovary and testis of mammals, indicating a direct effect for ghrelin in the control of reproduction. Ghrelin regulates mammalian reproduction by modulating hormone secretion from the brain and pituitary, and by acting directly on the gonads to influence reproductive tissue development and steroid hormone release. Based on the studies reported so far, ghrelin seems to have a predominantly inhibitory role on mammalian reproduction. The presence of ghrelin and ghrelin receptor has been found in the brain, pituitary and gonads of several non-mammalian vertebrates. In contrast to mammals, ghrelin seems to have a stimulatory role in the regulation of non-mammalian reproduction. The main objective of this review is to do a perspective analysis of the comparative aspects of ghrelin regulation of reproduction. (c) 2009 Elsevier Inc. All rights reserved.

  1. 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

    secretory stage on postnatal day 2, (ii conversion of calcium phosphates to apatite, peak protein folding and stress protein counts, and increased cytoskeletal protein levels such as actin and tubulin on day 4, as well as (iii secondary structure changes, isomerase activity, highest amelogenin levels, and peak phosphate/carbonate incorporation between postnatal days 6 and 8. Together, this study provides a baseline for a comprehensive understanding of the mineralogic and proteomic events that contribute to the complexity of mammalian tooth enamel development.

  2. Complex brain networks: From topological communities to clustered

    Indian Academy of Sciences (India)

    Complex brain networks: From topological communities to clustered dynamics ... Recent research has revealed a rich and complicated network topology in the cortical connectivity of mammalian brains. ... Pramana – Journal of Physics | News.

  3. 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.

  4. Bioenergetics of mammalian sperm capacitation.

    Science.gov (United States)

    Ferramosca, Alessandra; Zara, Vincenzo

    2014-01-01

    After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.

  5. Postnatal Vitamin D Intake Modulates Hippocampal Learning and Memory in Adult Mice.

    Science.gov (United States)

    Liang, Qiujuan; Cai, Chunhui; Duan, Dongxia; Hu, Xinyu; Hua, Wanhao; Jiang, Peicheng; Zhang, Liu; Xu, Jun; Gao, Zhengliang

    2018-01-01

    Vitamin D (VD) is a neuroactive steroid crucial for brain development, function and homeostasis. Its deficiency is associated with numerous brain conditions. As such, VD and its variants are routinely taken by a broad of groups with/without known VD deficiency. In contrast, the harmful effects of VD overdose have been poorly studied. Similarly, the developmental stage-specific VD deficiency and overdose have been rarely explored. In the present work, we showed that postnatal VD supplementation enhanced the motor function transiently in the young adult, but not in the older one. Postnatal VD intake abnormality did not impact the anxiety and depressive behavior but was detrimental to spatial learning and hippocampus-dependent memory. At the molecular level we failed to observe an obvious and constant change with the neural development and activity-related genes examined. However, disrupted developmental expression dynamics were observed for most of the genes, suggesting that the altered neural development dynamics and therefore aberrant adult plasticity might underlie the functional deficits. Our work highlights the essence of VD homeostasis in neural development and adult brain function. Further studies are needed to determine the short- and long-term effects VD intake status may have on brain development, homeostasis, and diseases.

  6. Postnatal Vitamin D Intake Modulates Hippocampal Learning and Memory in Adult Mice

    Directory of Open Access Journals (Sweden)

    Qiujuan Liang

    2018-04-01

    Full Text Available Vitamin D (VD is a neuroactive steroid crucial for brain development, function and homeostasis. Its deficiency is associated with numerous brain conditions. As such, VD and its variants are routinely taken by a broad of groups with/without known VD deficiency. In contrast, the harmful effects of VD overdose have been poorly studied. Similarly, the developmental stage-specific VD deficiency and overdose have been rarely explored. In the present work, we showed that postnatal VD supplementation enhanced the motor function transiently in the young adult, but not in the older one. Postnatal VD intake abnormality did not impact the anxiety and depressive behavior but was detrimental to spatial learning and hippocampus-dependent memory. At the molecular level we failed to observe an obvious and constant change with the neural development and activity-related genes examined. However, disrupted developmental expression dynamics were observed for most of the genes, suggesting that the altered neural development dynamics and therefore aberrant adult plasticity might underlie the functional deficits. Our work highlights the essence of VD homeostasis in neural development and adult brain function. Further studies are needed to determine the short- and long-term effects VD intake status may have on brain development, homeostasis, and diseases.

  7. Psychosocial factors associated with paternal postnatal depression.

    Science.gov (United States)

    Demontigny, Francine; Girard, Marie-Eve; Lacharité, Carl; Dubeau, Diane; Devault, Annie

    2013-08-15

    While maternal postpartum depression is a well-known phenomenon, paternal postnatal depression has been less studied. It is known that paternal postnatal depression impacts on children's and families' development, affects marital satisfaction and affects the economic health of industrialized countries. The aim of this study was to identify the psychosocial factors associated with paternal postnatal depression. A descriptive-correlational study was conducted with a sample of fathers of infants (average age: 11 months) who were breastfed exclusively or predominantly for at least 6 months, comparing psychosocial factors in fathers with (n: 17, 8.2%) and without a positive score for depression on the EPDS scale (n: 188). Psychosocial factors were assessed through questionnaires. Depression in fathers of breastfed infants is associated with the experience of perinatal loss in a previous pregnancy, parenting distress, infant temperament (difficult child), dysfunctional interactions with the child, decreased marital adjustment and perceived low parenting efficacy. Multivariate analysis suggests an independent effect of psychosocial factors such as parenting distress, quality of the marital relationship and perceived parenting efficacy on paternal depression. The sample focused on fathers of breastfed infant, since breastfeeding has become the feeding norm, and this should be taken into account when considering the generalization of findings. These findings emphasize the need to consider a set of psychosocial factors when examining fathers' mental health in the first year of a child's birth. Health professionals can enhance parenting efficacy and alleviate parenting distress by supporting fathers' unique experiences and addressing their needs. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs

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    Philipp eHohenbrink

    2014-09-01

    Full Text Available The vomeronasal organ (VNO is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR genes comprise two families of chemosensory genes (V1R and V2R that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the grey mouse lemur (Microcebus murinus, the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83% – 97% of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29% to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information.

  9. Brain transcriptome atlases : A computational perspective

    NARCIS (Netherlands)

    Mahfouz, A.M.E.T.A.; Huisman, S.M.H.; Lelieveldt, B.P.F.; Reinders, M.J.T.

    2017-01-01

    The immense complexity of the mammalian brain is largely reflected in the underlying molecular signatures of its billions of cells. Brain transcriptome atlases provide valuable insights into gene expression patterns across different brain areas throughout the course of development. Such atlases

  10. Perinatal and early postnatal changes in the expression of monocarboxylate transporters MCT1 and MCT2 in the rat forebrain.

    Science.gov (United States)

    Baud, Olivier; Fayol, Laurence; Gressens, Pierre; Pellerin, Luc; Magistretti, Pierre; Evrard, Philippe; Verney, Catherine

    2003-10-20

    In addition to glucose, monocarboxylates including lactate represent a major source of energy for the brain, especially during development. We studied the immunocytochemical expression of the monocarboxylate transporters MCT1 and MCT2 in the rat brain between embryonic day (E) 16 and postnatal day (P) 14. At E16-18, MCT1-like immunoreactivity was found throughout the cortical anlage, being particularly marked medially in the hippocampal anlage next to the ventricle. In a complementary pattern, MCT2-like immunoreactivity was expressed along the medial and ventral border of the ventricle in the medial septum and habenula before birth. The hypothalamic area exhibited MCT2 and MCT1 positive areas from E18 on. These transient labelings revealed four main sites of monocarboxylate and/or glucose exchange: the brain parenchyma, the epithelial cells, the ependymocytes, and the glia limitans. During the first postnatal week, MCT1 immunoreactivity extended massively to the vessel walls and moderately to the developing astrocytes in the cortex. In contrast, MCT2 immunoreactivity was faint in blood vessels but massive in developing astrocytes from P3 to P7. Neither MCT2 nor MCT1 colocalized with neuronal, microglial, or oligodendrocytic markers during the first postnatal week. At P14, a part of the scattered punctate MCT2 staining could be associated with astrocytes and postsynaptic dendritic labeling. The transient pattern of expression of MCTs throughout the perinatal period suggests a potential relationship with the maturation of the blood-brain barrier. Copyright 2003 Wiley-Liss, Inc.

  11. Evolutionary patterns of RNA-based duplication in non-mammalian chordates.

    Directory of Open Access Journals (Sweden)

    Ming Chen

    Full Text Available The role of RNA-based duplication, or retroposition, in the evolution of new gene functions in mammals, plants, and Drosophila has been widely reported. However, little is known about RNA-based duplication in non-mammalian chordates. In this study, we screened ten non-mammalian chordate genomes for retrocopies and investigated their evolutionary patterns. We identified numerous retrocopies in these species. Examination of the age distribution of these retrocopies revealed no burst of young retrocopies in ancient chordate species. Upon comparing these non-mammalian chordate species to the mammalian species, we observed that a larger fraction of the non-mammalian retrocopies was under strong evolutionary constraints than mammalian retrocopies are, as evidenced by signals of purifying selection and expression profiles. For the Western clawed frog, Medaka, and Sea squirt, many retrogenes have evolved gonad and brain expression patterns, similar to what was observed in human. Testing of retrogene movement in the Medaka genome, where the nascent sex chrosomes have been well assembled, did not reveal any significant gene movement. Taken together, our analyses demonstrate that RNA-based duplication generates many functional genes and can make a significant contribution to the evolution of non-mammalian genomes.

  12. THE GERMLINE STEM CELL NICHE UNIT IN MAMMALIAN TESTES

    Science.gov (United States)

    Oatley, Jon M.; Brinster, Ralph L.

    2014-01-01

    This review addresses current understanding of the germline stem cell niche unit in mammalian testes. Spermatogenesis is a classic model of tissue-specific stem cell function relying on self-renewal and differentiation of spermatogonial stem cells (SSCs). These fate decisions are influenced by a niche microenvironment composed of a growth factor milieu that is provided by several testis somatic support cell populations. Investigations over the last two decades have identified key determinants of the SSC niche including cytokines that regulate SSC functions and support cells providing these factors, adhesion molecules that influence SSC homing, and developmental heterogeneity of the niche during postnatal aging. Emerging evidence suggests that Sertoli cells are a key support cell population influencing the formation and function of niches by secreting soluble factors and possibly orchestrating contributions of other support cells. Investigations with mice have shown that niche influence on SSC proliferation differs during early postnatal development and adulthood. Moreover, there is mounting evidence of an age-related decline in niche function, which is likely influenced by systemic factors. Defining the attributes of stem cell niches is key to developing methods to utilize these cells for regenerative medicine. The SSC population and associated niche comprise a valuable model system for study that provides fundamental knowledge about the biology of tissue-specific stem cells and their capacity to sustain homeostasis of regenerating tissue lineages. While the stem cell is essential for maintenance of all self-renewing tissues and has received considerable attention, the role of niche cells is at least as important and may prove to be more receptive to modification in regenerative medicine. PMID:22535892

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

    Science.gov (United States)

    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.

  14. SVCT2 vitamin C transporter expression in progenitor cells of the postnatal neurogenic niche

    Science.gov (United States)

    Pastor, Patricia; Cisternas, Pedro; Salazar, Katterine; Silva-Alvarez, Carmen; Oyarce, Karina; Jara, Nery; Espinoza, Francisca; Martínez, Agustín D.; Nualart, Francisco

    2013-01-01

    Known as a critical antioxidant, recent studies suggest that vitamin C plays an important role in stem cell generation, proliferation and differentiation. Vitamin C also enhances neural differentiation during cerebral development, a function that has not been studied in brain precursor cells. We observed that the rat neurogenic niche is structurally organized at day 15 of postnatal development, and proliferation and neural differentiation increase at day 21. In the human brain, a similar subventricular niche was observed at 1-month of postnatal development. Using immunohistochemistry, sodium-vitamin C cotransporter 2 (SVCT2) expression was detected in the subventricular zone (SVZ) and rostral migratory stream (RMS). Low co-distribution of SVCT2 and βIII-tubulin in neuroblasts or type-A cells was detected, and minimal co-localization of SVCT2 and GFAP in type-B or precursor cells was observed. Similar results were obtained in the human neurogenic niche. However, BrdU-positive cells also expressed SVCT2, suggesting a role of vitamin C in neural progenitor proliferation. Primary neurospheres prepared from rat brain and the P19 teratocarcinoma cell line, which forms neurospheres in vitro, were used to analyze the effect of vitamin C in neural stem cells. Both cell types expressed functional SVCT2 in vitro, and ascorbic acid (AA) induced their neural differentiation, increased βIII-tubulin and SVCT2 expression, and amplified vitamin C uptake. PMID:23964197

  15. A game of thrones: neural plasticity in mammalian social hierarchies.

    Science.gov (United States)

    Mooney, Skyler J; Peragine, Diana E; Hathaway, Georgia A; Holmes, Melissa M

    2014-01-01

    Social status is a key regulator of health and reproduction in mammals, including humans. Despite this, relatively little is known about how social status influences the mammalian brain. Furthermore, the extent to which status is an independent construct, i.e., not simply acting as a psychosocial stressor, is yet to be determined. Research to date reveals several promising mechanisms and/or systems associated with social status, including monoamine systems, hypothalamic neuroendocrine axes, and the hippocampus, though whether these differences are the cause or effect of status is often unclear. We review these candidates and propose how best to approach this research question in the future.

  16. Enhancer evolution across 20 mammalian species

    DEFF Research Database (Denmark)

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah

    2015-01-01

    The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders...... by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements....... These results provide important insight into the functional genetics underpinning mammalian regulatory evolution....

  17. 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.

  18. 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 ...

  19. Home births and postnatal practices in madagali, North.Eastern ...

    African Journals Online (AJOL)

    Background: Home births are common in resource poor countries and postnatal practices vary from one community to the other. Objective: To determine the proportion of home births, reasons for home delivery, and evaluate postnatal practices in Madagali, north.eastern Nigeria. Materials and Methods: This was a ...

  20. 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.

  1. Validation of the Edinburgh Postnatal Depression Scale on a cohort ...

    African Journals Online (AJOL)

    Posmatal depression occurs in 10 - 15% of women. The Edinburgh Postnatal Depression Scale (EPDS) is a ID-item self-report scale designed specifically as a screening instrument for the postnatal period. It was initially validated for use in the UK, but has subsequently been validated for other communities. It has not been ...

  2. Postnatal corticosteroids and risk of retinopathy of prematurity.

    Science.gov (United States)

    Movsas, Tammy Z; Spitzer, Alan R; Gewolb, Ira H

    2016-08-01

    To investigate the association between postnatal steroids and retinopathy of prematurity (ROP) in neonates born with birth weights at the limit of viability (large study cohort of critically low birth weight infants ROP was more common in neonates exposed to postnatal steroids. Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  3. 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.

  4. 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.

  5. 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

  6. Mutation in cultured mammalian cells

    International Nuclear Information System (INIS)

    Nakamura, N.; Okada, S.

    1982-01-01

    Mammalian cell cultures were exposed to gamma-rays at various dose rates. Dose-rate effects were observed in cultured somatic cells of the mouse for cell killing and mutations resistant to 6-thioguanine (TGsup(r)) and to methotrexate (MTXsup(r)). Linear quadratic model may be applied to cell killing and TGsup(r) mutations in some cases but can not explain the whole data. Results at low doses with far low dose-rate were not predictable from data at high doses with acute or chronic irradiation. Radioprotective effects of dimethyl sulfoxide were seen only after acute exposure but not after chronic one, suggesting that damages by indirect action of radiations may be potentially reparable by cells. TGsup(r) mutations seem to contain gross structural changes whereas MTXsup(r) ones may have smaller alterations. (Namekawa, K.)

  7. Interaction theory of mammalian mitochondria.

    Science.gov (United States)

    Nakada, K; Inoue, K; Hayashi, J

    2001-11-09

    We generated mice with deletion mutant mtDNA by its introduction from somatic cells into mouse zygotes. Expressions of disease phenotypes are limited to tissues expressing mitochondrial dysfunction. Considering that all these mice share the same nuclear background, these observations suggest that accumulation of the mutant mtDNA and resultant expressions of mitochondrial dysfunction are responsible for expression of disease phenotypes. On the other hand, mitochondrial dysfunction and expression of clinical abnormalities were not observed until the mutant mtDNA accumulated predominantly. This protection is due to the presence of extensive and continuous interaction between exogenous mitochondria from cybrids and recipient mitochondria from embryos. Thus, we would like to propose a new hypothesis on mitochondrial biogenesis, interaction theory of mitochondria: mammalian mitochondria exchange genetic contents, and thus lost the individuality and function as a single dynamic cellular unit. Copyright 2001 Academic Press.

  8. Producing Newborn Synchronous Mammalian Cells

    Science.gov (United States)

    Gonda, Steve R.; Helmstetter, Charles E.; Thornton, Maureen

    2008-01-01

    A method and bioreactor for the continuous production of synchronous (same age) population of mammalian cells have been invented. The invention involves the attachment and growth of cells on an adhesive-coated porous membrane immersed in a perfused liquid culture medium in a microgravity analog bioreactor. When cells attach to the surface divide, newborn cells are released into the flowing culture medium. The released cells, consisting of a uniform population of synchronous cells are then collected from the effluent culture medium. This invention could be of interest to researchers investigating the effects of the geneotoxic effects of the space environment (microgravity, radiation, chemicals, gases) and to pharmaceutical and biotechnology companies involved in research on aging and cancer, and in new drug development and testing.

  9. Mammalian gastrointestinal parasites in rainforest remnants

    Indian Academy of Sciences (India)

    Here, we studied the gastrointestinal parasites of nonhuman mammalian hosts living in 10 rainforest patches of the Anamalai Tiger Reserve, India. We examined 349 faecal samples of 17 mammalian species and successfully identified 24 gastroin-testinal parasite taxa including 1 protozoan, 2 trematode, 3 cestode and 18 ...

  10. Active zones of mammalian neuromuscular junctions: formation, density, and aging.

    Science.gov (United States)

    Nishimune, Hiroshi

    2012-12-01

    Presynaptic active zones are synaptic vesicle release sites that play essential roles in the function and pathology of mammalian neuromuscular junctions (NMJs). The molecular mechanisms of active zone organization use presynaptic voltage-dependent calcium channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the muscle-derived synapse organizer, laminin β2 and interact intracellularly with active zone-specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P/Q- and N-type VDCCs double-knockout mice, and they are consistent with the pathological conditions of Lambert-Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin β2 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies. © 2012 New York Academy of Sciences.

  11. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  12. Postnatal changes in the nitric oxide system of the rat cerebral cortex after hypoxia during delivery.

    Science.gov (United States)

    Fernández, Ana Patricia; Alonso, David; Lisazoaín, Ignacio; Serrano, Julia; Leza, Juan Carlos; Bentura, María Luisa; López, Juan Carlos; Manuel Encinas, Juan; Fernández-Vizarra, Paula; Castro-Blanco, Susana; Martínez, Alfredo; Martinez-Murillo, Ricardo; Lorenzo, Pedro; Pedrosa, Juan Angel; Peinado, María Angeles; Rodrigo, José

    2003-05-14

    The impact of hypoxia in utero during delivery was correlated with the immunocytochemistry, expression and activity of the neuronal (nNOS) and inducible (iNOS) isoforms of the nitric oxide synthase enzyme as well as with the reactivity and expression of nitrotyrosine as a marker of protein nitration during early postnatal development of the cortex. The expression of nNOS in both normal and hypoxic animals increased during the first few postnatal days, reaching a peak at day P5, but a higher expression was consistently found in hypoxic brain. This expression decreased progressively from P7 to P20, but was more prominent in the hypoxic group. Immunoreactivity for iNOS was also higher in the cortex of the hypoxic rats and was more evident between days P0 and P5, decreasing dramatically between P10 and P20 in both groups of rats. Two nitrated proteins of 52 and 38 kDa, were also identified. Nitration of the 52-kDa protein was more intense in the hypoxic animals than in the controls, increasing from P0 to P7 and then decreasing progressively to P20. The 38-kDa nitrated protein was seen only from P10 to P20, and its expression was more intense in control than in the hypoxic group. These results suggest that the NO system may be involved in neuronal maturation and cortical plasticity over postnatal development. Overproduction of NO in the brain of hypoxic animals may constitute an effort to re-establish normal blood flow and may also trigger a cascade of free-radical reactions, leading to modifications in the cortical plasticity.

  13. Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats.

    Science.gov (United States)

    Odeon, María Mercedes; Andreu, Marcela; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2015-01-01

    Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of voluntary alcohol intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, pups were separated from their mothers and exposed to cold stress (4 °C) for 1 h daily for 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5-7 rats per group), then killed. CPS: (1) increased voluntary ethanol intake, (2) did not affect body weight gain or produce signs of toxicity with alcohol exposure, (3) increased glutamate uptake by hippocampal synaptosomes in vitro and (4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to prevent enlarged extracellular glutamate levels is inferred. Although CPS strongly increased intake of ethanol, this had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood.

  14. 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.

  15. Postnatal Gene Therapy Improves Spatial Learning Despite the Presence of Neuronal Ectopia in a Model of Neuronal Migration Disorder

    Directory of Open Access Journals (Sweden)

    Huaiyu Hu

    2016-11-01

    Full Text Available Patients with type II lissencephaly, a neuronal migration disorder with ectopic neurons, suffer from severe mental retardation, including learning deficits. There is no effective therapy to prevent or correct the formation of neuronal ectopia, which is presumed to cause cognitive deficits. We hypothesized that learning deficits were not solely caused by neuronal ectopia and that postnatal gene therapy could improve learning without correcting the neuronal ectopia formed during fetal development. To test this hypothesis, we evaluated spatial learning of cerebral cortex-specific protein O-mannosyltransferase 2 (POMT2, an enzyme required for O-mannosyl glycosylation knockout mice and compared to the knockout mice that were injected with an adeno-associated viral vector (AAV encoding POMT2 into the postnatal brains with Barnes maze. The data showed that the knockout mice exhibited reduced glycosylation in the cerebral cortex, reduced dendritic spine density on CA1 neurons, and increased latency to the target hole in the Barnes maze, indicating learning deficits. Postnatal gene therapy restored functional glycosylation, rescued dendritic spine defects, and improved performance on the Barnes maze by the knockout mice even though neuronal ectopia was not corrected. These results indicate that postnatal gene therapy improves spatial learning despite the presence of neuronal ectopia.

  16. 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

  17. Ablation of BRaf impairs neuronal differentiation in the postnatal hippocampus and cerebellum.

    Directory of Open Access Journals (Sweden)

    Verena Pfeiffer

    Full Text Available This study focuses on the role of the kinase BRaf in postnatal brain development. Mice expressing truncated, non-functional BRaf in neural stem cell-derived brain tissue demonstrate alterations in the cerebellum, with decreased sizes and fuzzy borders of the glomeruli in the granule cell layer. In addition we observed reduced numbers and misplaced ectopic Purkinje cells that showed an altered structure of their dendritic arborizations in the hippocampus, while the overall cornus ammonis architecture appeared to be unchanged. In male mice lacking BRaf in the hippocampus the size of the granule cell layer was normal at postnatal day 12 (P12 but diminished at P21, as compared to control littermates. This defect was caused by a reduced ability of dentate gyrus progenitor cells to differentiate into NeuN positive granule cell neurons. In vitro cell culture of P0/P1 hippocampal cells revealed that BRaf deficient cells were impaired in their ability to form microtubule-associated protein 2 positive neurons. Together with the alterations in behaviour, such as autoaggression and loss of balance fitness, these observations indicate that in the absence of BRaf all neuronal cellular structures develop, but neuronal circuits in the cerebellum and hippocampus are partially disturbed besides impaired neuronal generation in both structures.

  18. Lack of toxic effect of technical azadirachtin during postnatal development of rats.

    Science.gov (United States)

    Srivastava, M K; Raizada, R B

    2007-03-01

    Azadirachtin, a biopesticide has been evaluated for its possible toxic effects during postnatal development of rats over two generations. Rats were fed 100, 500 and 1000ppm technical azadirachtin through diet which is equivalent to 5, 25 and 50mg/kg body weight of rats. Technical azadirachtin has not produced any adverse effects on reproductive function and data were comparable to control animals over two generations. There were no toxicological effect in parent rats as evidenced by clinical signs of toxicity, enzymatic parameters like AST, ALT, ALP, S. bilirubin, S. cholesterol, total protein and histopathology of liver, brain, kidney and testes/ovary. The litters of F(1B) and F(2B) generations were devoid of any morphological, visceral and teratological changes. The percent cumulative loss and growth index of pups were also comparable to respective controls in successive growth period of 0, 4, 7, 14 and 21 days in two generations. There were no major malformations in fetuses while some insignificant minor skeletal variations like missing 5th sternebrae and bipartite thoracic centre found were not compound or dose related. No significant pathomorphological changes were observed in liver, kidney, brain and gonads of F(2B) pups. In conclusion rats fed technical azadirachtin showed no evidence of cumulative effects on postnatal development and reproductive performance over two generations. Absence of any major adverse reproductive effects in adults as well as in 21 days old pups of F(2B) generation suggest the safe use of technical azadirachtin as a biopesticide.

  19. PHYSIOTHERAPY EXERCISES DURING ANTENATAL AND POSTNATAL

    Directory of Open Access Journals (Sweden)

    Hannah Rajsekhar

    2015-10-01

    Full Text Available Background: It’s a well-known fact that exercise is good for the mind and body making it beneficial for expectant and new mothers. The challenge of pregnancy, labor and looking after a new born is not an easy task. So the fitter you are the better you will cope with this life changing event. Method: Aerobic and strengthening exercises help in adjusting to the increasing weight and posture changes to cope effectively with the labor and the postnatal period. Although exercises in pregnancy are extremely beneficial, they can cause more harm than good if not done correctly. Medical screening for exercise should be done by the Doctor as well as the Physiotherapist to ensure that the patient underwent a basic screening, assessment or continued monitoring for the right exercise protocol for avoidance of any complications and to ensure the benefits of staying healthy and fit. Results: Evidence shows that exercise training programs designed and delivered by the Physiotherapists can relieve the prenatal post natal problems. Conclusion: Number of studies has shown the positive effects of aerobic and strengthening exercises on pregnant women. The physical changes to a pregnant woman’s body are multiple. There are center of mass changes, pressure on the organs and increased weight gain. In fact, over two thirds of pregnant women experience back pain, one fifth experience pelvic pain and over 40% experience urinary incontinence in their first pregnancy.

  20. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

    Science.gov (United States)

    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

    2016-01-01

    Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

  1. Intrinsic electrical properties of mammalian neurons and CNS function: a historical perspective

    Science.gov (United States)

    Llinás, Rodolfo R.

    2014-01-01

    This brief review summarizes work done in mammalian neuroscience concerning the intrinsic electrophysiological properties of four neuronal types; Cerebellar Purkinje cells, inferior olivary cells, thalamic cells, and some cortical interneurons. It is a personal perspective addressing an interesting time in neuroscience when the reflex view of brain function, as the paradigm to understand global neuroscience, began to be modified toward one in which sensory input modulates rather than dictates brain function. The perspective of the paper is not a comprehensive description of the intrinsic electrical properties of all nerve cells but rather addresses a set of cell types that provide indicative examples of mechanisms that modulate brain function. PMID:25408634

  2. INTRINSIC ELECTRICAL PROPERTIES OF MAMMALIAN NEURONS AND CNS FUNCTION: A HISTORICAL PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Rodolfo R Llinas

    2014-11-01

    Full Text Available This brief review summarizes work done in mammalian neuroscience concerning the intrinsic electrophysiological properties of four neuronal types; Cerebellar Purkinje cells, inferior olivary cells, thalamic cells, and some cortical interneurons. It is a personal perspective addressing an interesting time in neuroscience when the reflex view of brain function, as the paradigm to understand global neuroscience, began to be modified towards one in which sensory input modulates rather than dictates brain function. The perspective of the paper is not a comprehensive description of the intrinsic electrical properties of all nerve cells but rather addresses a set of cell types that provide indicative examples of mechanisms that modulate brain function.

  3. 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.

  4. Aquaporin-1 in the choroid plexuses of developing mammalian brain

    DEFF Research Database (Denmark)

    Johansson, P.A.; Dziegielewska, K.M.; Ek, C.J.

    2005-01-01

    Cerebrospinal fluid, Cerebral ventricles, Blood-CSF barrier, Water transport, Fetus, Human, Rat (Sprague Dawley)......Cerebrospinal fluid, Cerebral ventricles, Blood-CSF barrier, Water transport, Fetus, Human, Rat (Sprague Dawley)...

  5. Postnatal growth, age estimation and development of foraging ...

    Indian Academy of Sciences (India)

    Unknown

    mothers. There was no significant difference in the growth pattern of the young maintained in captivity compared ..... interactions, and development of vocalizations in the vesper- ... Kunz T H and Hood W R 2000 Parental care and postnatal.

  6. BMP signaling regulates satellite cell-dependent postnatal muscle growth.

    Science.gov (United States)

    Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

    2017-08-01

    Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  7. 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

  8. 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

  9. Prenatal and postnatal depression among low income Brazilian women

    Directory of Open Access Journals (Sweden)

    V.A. Da-Silva

    1998-06-01

    Full Text Available Postnatal depression is a significant problem affecting 10-15% of mothers in many countries and has been the subject of an increasing number of publications. Prenatal depression has been studied less. The aims of the present investigation were: 1 to obtain information on the prevalence of prenatal and postnatal depression in low income Brazilian women by using an instrument already employed in several countries, i.e., the Edinburgh Postnatal Depression Scale (EPDS; 2 to evaluate the risk factors involved in prenatal and postnatal depression in Brazil. The study groups included 33 pregnant women interviewed at home during the second and third trimesters of pregnancy, and once a month during the first six months after delivery. Questions on life events and the mother's relationship with the baby were posed during each visit. Depressed pregnant women received less support from their partners than non-depressed pregnant women (36.4 vs 72.2%, P<0.05; Fisher exact test. Black women predominated among pre- and postnatally depressed subjects. Postnatal depression was associated with lower parity (0.4 ± 0.5 vs 1.1 ± 1.0, P<0.05; Student t-test. Thus, the period of pregnancy may be susceptible to socio-environmental factors that induce depression, such as the lack of affective support from the partner. The prevalence rate of 12% observed for depression in the third month postpartum is comparable to that of studies from other countries.

  10. Mammalian synthetic biology: emerging medical applications.

    Science.gov (United States)

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-06

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  11. Mammalian Sperm Motility: Observation and Theory

    KAUST Repository

    Gaffney, E.A.; Gadê lha, H.; Smith, D.J.; Blake, J.R.; Kirkman-Brown, J.C.

    2011-01-01

    the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian

  12. Enhancer Evolution across 20 Mammalian Species

    Science.gov (United States)

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim F.; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan T.; Jasinska, Anna J.; Turner, James M.A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

    2015-01-01

    Summary The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution. PMID:25635462

  13. The use of Edinburgh Postnatal Depression Scale to identify postnatal depression symptoms at well child visit

    Directory of Open Access Journals (Sweden)

    Silvestri Maria

    2009-10-01

    Full Text Available Abstract Objectives 1 to evaluate the role of the pediatrician in detecting postnatal depression (PD symptoms by the Edinburgh Postnatal Depression Scale (EPDS; 2 to detect factors increasing the risk of PD and, 3 to assess the importance of scores gained from fathers' questionnaire. Methods we surveyed 1122 mothers and 499 fathers who were assessed using the EPDS during the first well-child visit. After 5 weeks, high scoring parents, completed a second EPDS. High scoring parents were examined by a psychiatrist who had to confirm the PD diagnosis. Results 26.6% of mothers and 12.6% of fathers at the first visit, 19.0% of mothers and 9.1% of fathers at the second visit, gained scores signaling the risk of PD. Four mothers and two fathers had confirmed PD diagnosis. Younger maternal age, non-Italian nationality and low socio-economic condition were related to higher EPDS scores. Conclusion PD is common in the average population. Using a simple and standardized instrument, pediatricians are able to detect parents with higher risk of suffering from PD.

  14. Mammalian Genetics and Teratology Section

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    The work of the Mammalian Genetics and Teratology Section includes research in mutagenesis, basic genetics, reproductive biology, and teratogenesis involving basic studies, method development, including exploration of the biological material, and testing. The basic studies make good use of the genetic material accumulated in mutagenesis experiments of various kinds, or of the findings of mutagenesis experiments themselves. In the latter category is the finding of a repair system in the fertilized egg. The genetics of repair competency or deficiency are now under study. A linear relationship between gene dosage and level of expression of an enzyme has been demonstrated. Opportunities for the study of gene action are provided by a number of X-autosome translocations which continue to be discovered in the course of mutagenesis experiments. In these rearrangements, X-chromosome inactivation extends to neighboring autosomal loci. Considerable progress has been made in developing the skeletal mutation system, which provides information on dominants that is highly useful for risk assessment. A sensitive-indicator test is now under development which will make the screening for skeletal mutations much faster and easier. Method development has also progressed on the in vivo somatic-mutation test now being widely used as an in vivo screen for mutagens. Another method developed here is the numerical sex-chromosome anomaly (NSA) test for nondisjunction. The NSA method is being used to explore the effects of female age on chromosome loss and nondisjunction. A model for estimating the misclassification error was experimentally established for the heritable translocation test. A rapid, easy, and sensitive in vivo screening test for teratogenesis was developed. An in vitro teratogenic prescreen being developed makes use of teratocarcinoma-derived cell lines

  15. Effect of cadmium on lipid metabolism of brain

    International Nuclear Information System (INIS)

    Gulati, S.; Gill, K.D.; Nath, R.

    1987-01-01

    The effect of early postnatal cadmium exposure on the in vivo incorporation of (1- 14 C) sodium acetate into various lipid classes of the weanling rat brain was studied. A stimulated incorporation of the label was observed in total lipids, phospholipids, cholesterol, cerebrosides and sulphatides of the brain of Cd-exposed animals compared to controls. (author)

  16. Postnatal odorant exposure induces peripheral olfactory plasticity at the cellular level.

    Science.gov (United States)

    Cadiou, Hervé; Aoudé, Imad; Tazir, Bassim; Molinas, Adrien; Fenech, Claire; Meunier, Nicolas; Grosmaitre, Xavier

    2014-04-02

    Mammalian olfactory sensory neurons (OSNs) form the primary elements of the olfactory system. Inserted in the olfactory mucosa lining of the nasal cavity, they are exposed to the environment and their lifespan is brief. Several reports say that OSNs are regularly regenerated during the entire life and that odorant environment affects the olfactory epithelium. However, little is known about the impact of the odorant environment on OSNs at the cellular level and more precisely in the context of early postnatal olfactory exposure. Here we exposed MOR23-green fluorescent protein (GFP) and M71-GFP mice to lyral or acetophenone, ligands for MOR23 or M71, respectively. Daily postnatal exposure to lyral induces plasticity in the population of OSNs expressing MOR23. Their density decreases after odorant exposure, whereas the amount of MOR23 mRNA and protein remain stable in the whole epithelium. Meanwhile, quantitative PCR indicates that each MOR23 neuron has higher levels of olfactory receptor transcripts and also expresses more CNGA2 and phosphodiesterase 1C, fundamental olfactory transduction pathway proteins. Transcript levels return to baseline after 4 weeks recovery. Patch-clamp recordings reveal that exposed MOR23 neurons respond to lyral with higher sensitivity and broader dynamic range while the responses' kinetics were faster. These effects are specific to the odorant-receptor pair lyral-MOR23: there was no effect of acetophenone on MOR23 neurons and no effect of acetophenone and lyral on the M71 population. Together, our results clearly demonstrate that OSNs undergo specific anatomical, molecular, and functional adaptation when chronically exposed to odorants in the early stage of life.

  17. Changes in RFamide-Related Peptide-1 (RFRP-1)-Immunoreactivity During Postnatal Development and the Estrous Cycle

    DEFF Research Database (Denmark)

    Jørgensen, Sara R; Andersen, Mille D; Overgaard, Agnete

    2014-01-01

    and inhibit GnRH neurons. The RFRP precursor is processed into 2 mature peptides, RFRP-1 and RFRP-3. These are characterized by a conserved C-terminal motif RF-NH2 but display highly different N termini. Even though the 2 peptides are equally potent in vitro, little is known about their relative distribution...... and their distinct roles in vivo. In this study, we raised an antiserum selective for RFRP-1 and defined the distribution of RFRP-1-immunoreactive (ir) neurons in the rat brain. Next, we analyzed the level of RFRP-1-ir during postnatal development in males and females and investigated changes in RFRP-1-ir during....... The number of RFRP-1-ir neurons and the density of cellular immunoreactivity were unchanged from juvenile to adulthood in male rats during the postnatal development. However, both parameters were significantly increased in female rats from peripuberty to adulthood, demonstrating prominent gender difference...

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

    Science.gov (United States)

    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

  19. 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

  20. Transgenic APP expression during postnatal development causes persistent locomotor hyperactivity in the adult.

    Science.gov (United States)

    Rodgers, Shaefali P; Born, Heather A; Das, Pritam; Jankowsky, Joanna L

    2012-06-18

    Transgenic mice expressing disease-associated proteins have become standard tools for studying human neurological disorders. Transgenes are often expressed using promoters chosen to drive continuous high-level expression throughout life rather than temporal and spatial fidelity to the endogenous gene. This approach has allowed us to recapitulate diseases of aging within the two-year lifespan of the laboratory mouse, but has the potential for creating aberrant phenotypes by mechanisms unrelated to the human disorder. We show that overexpression of the Alzheimer's-related amyloid precursor protein (APP) during early postnatal development leads to severe locomotor hyperactivity that can be significantly attenuated by delaying transgene onset until adulthood. Our data suggest that exposure to transgenic APP during maturation influences the development of neuronal circuits controlling motor activity. Both when matched for total duration of APP overexpression and when matched for cortical amyloid burden, animals exposed to transgenic APP as juveniles are more active in locomotor assays than animals in which APP overexpression was delayed until adulthood. In contrast to motor activity, the age of APP onset had no effect on thigmotaxis in the open field as a rough measure of anxiety, suggesting that the interaction between APP overexpression and brain development is not unilateral. Our findings indicate that locomotor hyperactivity displayed by the tet-off APP transgenic mice and several other transgenic models of Alzheimer's disease may result from overexpression of mutant APP during postnatal brain development. Our results serve as a reminder of the potential for unexpected interactions between foreign transgenes and brain development to cause long-lasting effects on neuronal function in the adult. The tet-off APP model provides an easy means of avoiding developmental confounds by allowing transgene expression to be delayed until the mice reach adulthood.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Immunologic differentiation of two high-affinity neurotensin receptor isoforms in the developing rat brain.

    Science.gov (United States)

    Boudin, H; Lazaroff, B; Bachelet, C M; Pélaprat, D; Rostène, W; Beaudet, A

    2000-09-11

    Earlier studies have demonstrated overexpression of NT1 neurotensin receptors in rat brain during the first 2 weeks of life. To gain insight into this phenomenon, we investigated the identity and distribution of NT1 receptor proteins in the brain of 10-day-old rats by using two different NT1 antibodies: one (Abi3) directed against the third intracellular loop and the other (Abi4) against the C-terminus of the receptor. Immunoblot experiments that used Abi3 revealed the presence of two differentially glycosylated forms of the NT1 receptor in developing rat brain: one migrating at 54 and the other at 52 kDa. Whereas the 54-kDa form was expressed from birth to adulthood, the 52-kDa form was detected only at 10 and 15 days postnatal. Only the 52-kDa isoform was recognized by Abi4. By immunohistochemistry, both forms of the receptor were found to be predominantly expressed in cerebral cortex and dorsal hippocampus, in keeping with earlier radioligand binding and in situ hybridization data. However, whereas Abi4 immunoreactivity was mainly concentrated within nerve cell bodies and extensively colocalized with the Golgi marker alpha-mannosidase II, Abi3 immunoreactivity was predominantly located along neuronal processes. These results suggest that the transitorily expressed 52-kDa protein corresponds to an immature, incompletely glycosylated and largely intracellular form of the NT1 receptor and that the 54-kDa protein corresponds to a mature, fully glycosylated, and largely membrane-associated form. They also indicate that antibodies directed against different sequences of G-protein-coupled receptors may yield isoform-specific immunohistochemical labeling patterns in mammalian brain. Finally, the selective expression of the short form of the NT1 receptor early in development suggests that it may play a specific role in the establishment of neuronal circuitry. Copyright 2000 Wiley-Liss, Inc.

  3. Glutamatergic synaptic currents of nigral dopaminergic neurons follow a postnatal developmental sequence

    Directory of Open Access Journals (Sweden)

    Edouard ePearlstein

    2015-05-01

    Full Text Available The spontaneous activity pattern of adult dopaminergic (DA neurons of the substantia nigra pars compacta (SNc results from interactions between intrinsic membrane conductances and afferent inputs. In adult SNc DA neurons, low-frequency tonic background activity is generated by intrinsic pacemaker mechanisms, whereas burst generation depends on intact synaptic inputs in particular the glutamatergic ones. Tonic DA release in the striatum during pacemaking is required to maintain motor activity, and burst firing evokes phasic DA release, necessary for cue-dependent learning tasks. However, it is still unknown how the firing properties of SNc DA neurons mature during postnatal development before reaching the adult state. We studied the postnatal developmental profile of spontaneous and evoked AMPA and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs in SNc DA neurons in brain slices from immature (postnatal days P4-10 and young adult (P30-50 tyrosine hydroxylase (TH-GFP mice. We found that somato-dendritic fields of SNc DA neurons are already mature at P4-10. In contrast, spontaneous glutamatergic EPSCs show a developmental sequence. Spontaneous NMDA EPSCs in particular are larger and more frequent in immature SNc DA neurons than in young adult ones and have a bursty pattern. They are mediated by GluN2B and GluN2D subunit-containing NMDA receptors. The latter generate long-lasting, DQP1105-sensitive, spontaneous EPSCs, which are transiently recorded during this early period. Due to high NMDA activity, immature SNc DA neurons generate large and long lasting NMDA receptor-dependent (APV-sensitive bursts in response to the stimulation of the subthalamic nucleus. We conclude that the transient high NMDA activity allows calcium influx into the dendrites of developing SNc DA neurons.

  4. Mammalian sleep dynamics: how diverse features arise from a common physiological framework.

    Directory of Open Access Journals (Sweden)

    Andrew J K Phillips

    2010-06-01

    Full Text Available Mammalian sleep varies widely, ranging from frequent napping in rodents to consolidated blocks in primates and unihemispheric sleep in cetaceans. In humans, rats, mice and cats, sleep patterns are orchestrated by homeostatic and circadian drives to the sleep-wake switch, but it is not known whether this system is ubiquitous among mammals. Here, changes of just two parameters in a recent quantitative model of this switch are shown to reproduce typical sleep patterns for 17 species across 7 orders. Furthermore, the parameter variations are found to be consistent with the assumptions that homeostatic production and clearance scale as brain volume and surface area, respectively. Modeling an additional inhibitory connection between sleep-active neuronal populations on opposite sides of the brain generates unihemispheric sleep, providing a testable hypothetical mechanism for this poorly understood phenomenon. Neuromodulation of this connection alone is shown to account for the ability of fur seals to transition between bihemispheric sleep on land and unihemispheric sleep in water. Determining what aspects of mammalian sleep patterns can be explained within a single framework, and are thus universal, is essential to understanding the evolution and function of mammalian sleep. This is the first demonstration of a single model reproducing sleep patterns for multiple different species. These wide-ranging findings suggest that the core physiological mechanisms controlling sleep are common to many mammalian orders, with slight evolutionary modifications accounting for interspecies differences.

  5. Epigenetics and brain evolution.

    Science.gov (United States)

    Keverne, Eric B

    2011-04-01

    Fundamental aspects of mammalian brain evolution occurred in the context of viviparity and placentation brought about by the epigenetic regulation of imprinted genes. Since the fetal placenta hormonally primes the maternal brain, two genomes in one individual are transgenerationally co-adapted to ensure maternal care and nurturing. Advanced aspects of neocortical brain evolution has shown very few genetic changes between monkeys and humans. Although these lineages diverged at approximately the same time as the rat and mouse (20 million years ago), synonymous sequence divergence between the rat and mouse is double that when comparing monkey with human sequences. Paradoxically, encephalization of rat and mouse are remarkably similar, while comparison of the human and monkey shows the human cortex to be three times the size of the monkey. This suggests an element of genetic stability between the brains of monkey and man with a greater emphasis on epigenetics providing adaptable variability.

  6. 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.

  7. The current status of evidence for and against postnatal oogenesis in mammals: a case of ovarian optimism versus pessimism?

    Science.gov (United States)

    Tilly, Jonathan L; Niikura, Yuichi; Rueda, Bo R

    2009-01-01

    Whether or not oogenesis continues in the ovaries of mammalian females during postnatal life was heavily debated from the late 1800s through the mid-1900s. However, in 1951 Lord Solomon Zuckerman published what many consider to be a landmark paper summarizing his personal views of data existing at the time for and against the possibility of postnatal oogenesis. In Zuckerman's opinion, none of the evidence he considered was inconsistent with Waldeyer's initial proposal in 1870 that female mammals cease production of oocytes at or shortly after birth. This conclusion rapidly became dogma, and remained essentially unchallenged until just recently, despite the fact that Zuckerman did not offer a single experiment proving that adult female mammals are incapable of oogenesis. Instead, 20 years later he reemphasized that his conclusion was based solely on an absence of data he felt would be inconsistent with the idea of a nonrenewable oocyte pool provided at birth. However, in the immortal words of Carl Sagan, an "absence of evidence is not evidence of absence." Indeed, building on the efforts of a few scientists who continued to question this dogma after Zuckerman's treatise in 1951, we reported several data sets in 2004 that were very much inconsistent with the widely held belief that germ cell production in female mammals ceases at birth. Perhaps not surprisingly, given the magnitude of the paradigm shift being proposed, this work reignited a vigorous debate that first began more than a century ago. Our purpose here is to review the experimental evidence offered in recent studies arguing support for and against the possibility that adult mammalian females replenish their oocyte reserve. "Never discourage anyone who continually makes progress, no matter how slow."-Plato (427-347 BC).

  8. Mosaic evolution of the mammalian auditory periphery.

    Science.gov (United States)

    Manley, Geoffrey A

    2013-01-01

    The classical mammalian auditory periphery, i.e., the type of middle ear and coiled cochlea seen in modern therian mammals, did not arise as one unit and did not arise in all mammals. It is also not the only kind of auditory periphery seen in modern mammals. This short review discusses the fact that the constituents of modern mammalian auditory peripheries arose at different times over an extremely long period of evolution (230 million years; Ma). It also attempts to answer questions as to the selective pressures that led to three-ossicle middle ears and the coiled cochlea. Mammalian middle ears arose de novo, without an intermediate, single-ossicle stage. This event was the result of changes in eating habits of ancestral animals, habits that were unrelated to hearing. The coiled cochlea arose only after 60 Ma of mammalian evolution, driven at least partly by a change in cochlear bone structure that improved impedance matching with the middle ear of that time. This change only occurred in the ancestors of therian mammals and not in other mammalian lineages. There is no single constellation of structural features of the auditory periphery that characterizes all mammals and not even all modern mammals.

  9. 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

  10. Problems of allometric scaling analysis: examples from mammalian reproductive biology.

    Science.gov (United States)

    Martin, Robert D; Genoud, Michel; Hemelrijk, Charlotte K

    2005-05-01

    Biological scaling analyses employing the widely used bivariate allometric model are beset by at least four interacting problems: (1) choice of an appropriate best-fit line with due attention to the influence of outliers; (2) objective recognition of divergent subsets in the data (allometric grades); (3) potential restrictions on statistical independence resulting from phylogenetic inertia; and (4) the need for extreme caution in inferring causation from correlation. A new non-parametric line-fitting technique has been developed that eliminates requirements for normality of distribution, greatly reduces the influence of outliers and permits objective recognition of grade shifts in substantial datasets. This technique is applied in scaling analyses of mammalian gestation periods and of neonatal body mass in primates. These analyses feed into a re-examination, conducted with partial correlation analysis, of the maternal energy hypothesis relating to mammalian brain evolution, which suggests links between body size and brain size in neonates and adults, gestation period and basal metabolic rate. Much has been made of the potential problem of phylogenetic inertia as a confounding factor in scaling analyses. However, this problem may be less severe than suspected earlier because nested analyses of variance conducted on residual variation (rather than on raw values) reveals that there is considerable variance at low taxonomic levels. In fact, limited divergence in body size between closely related species is one of the prime examples of phylogenetic inertia. One common approach to eliminating perceived problems of phylogenetic inertia in allometric analyses has been calculation of 'independent contrast values'. It is demonstrated that the reasoning behind this approach is flawed in several ways. Calculation of contrast values for closely related species of similar body size is, in fact, highly questionable, particularly when there are major deviations from the best

  11. Postnatal Deletion of Fat Storage-inducing Transmembrane Protein 2 (FIT2/FITM2) Causes Lethal Enteropathy.

    Science.gov (United States)

    Goh, Vera J; Tan, Jolene S Y; Tan, Bryan C; Seow, Colin; Ong, Wei-Yi; Lim, Yen Ching; Sun, Lei; Ghosh, Sujoy; Silver, David L

    2015-10-16

    Lipid droplets (LDs) are phylogenetically conserved cytoplasmic organelles that store neutral lipids within a phospholipid monolayer. LDs compartmentalize lipids and may help to prevent cellular damage caused by their excess or bioactive forms. FIT2 is a ubiquitously expressed transmembrane endoplasmic reticulum (ER) membrane protein that has previously been implicated in LD formation in mammalian cells and tissue. Recent data indicate that FIT2 plays an essential role in fat storage in an in vivo constitutive adipose FIT2 knock-out mouse model, but the physiological effects of postnatal whole body FIT2 depletion have never been studied. Here, we show that tamoxifen-induced FIT2 deletion using a whole body ROSA26CreER(T2)-driven FIT2 knock-out (iF2KO) mouse model leads to lethal intestinal pathology, including villus blunting and death of intestinal crypts, and loss of lipid absorption. iF2KO mice lose weight and die within 2 weeks after the first tamoxifen dose. At the cellular level, LDs failed to form in iF2KO enterocytes after acute oil challenge and instead accumulated within the ER. Intestinal bile acid transporters were transcriptionally dysregulated in iF2KO mice, leading to the buildup of bile acids within enterocytes. These data support the conclusion that FIT2 plays an essential role in regulating intestinal health and survival postnatally. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Postnatal arsenic exposure and attention impairment in school children.

    Science.gov (United States)

    Rodríguez-Barranco, Miguel; Gil, Fernando; Hernández, Antonio F; Alguacil, Juan; Lorca, Andres; Mendoza, Ramón; Gómez, Inmaculada; Molina-Villalba, Isabel; González-Alzaga, Beatriz; Aguilar-Garduño, Clemente; Rohlman, Diane S; Lacasaña, Marina

    2016-01-01

    Over the last few decades there has been an increased concern about the health risks from exposure to metallic trace elements, including arsenic, because of their potential neurotoxic effects on the developing brain. This study assessed whether urinary arsenic (UA) levels are associated with attention performance and Attention-Deficit/Hyperactivity Disorder (ADHD) in children living in an area with high industrial and mining activities in Southwestern Spain. A cross-sectional study was conducted on 261 children aged 6-9 years. Arsenic levels were determined in urine samples. Attention was measured by using 4 independent tools: a) tests from the Behavioral Assessment and Research System (BARS) designed to measure attention function: Simple Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT); b) AULA Test, a virtual reality (VR)-based test that evaluates children's response to several stimuli in an environment simulating a classroom; c) Child Behavior Checklist (CBCL), administered to parents; and d) Teacher's Report Form (TRF), administered to teachers. Multivariate linear and logistic regression models, adjusted for potential confounders, were used to estimate the magnitude of the association between UA levels and attention performance scores. Higher UA levels were associated with an increased latency of response in RTT (β = 12.3; 95% confidence interval (CI): 3.5-21.1) and SAT (β = 3.6; 95% CI: .4-6.8) as well as with worse performance on selective and focalized attention in the AULA test (β for impulsivity = .6; 95% CI: .1-1.1; β for inattention = .5; 95% CI: .03-1.0). A dose-response relationship was observed between UA levels and inattention and impulsivity scores. In contrast, results from the CBCL and TRF tests failed to show a significant association with UA levels. In conclusion, UA levels were associated with impaired attention/cognitive function, even at levels considered safe. These results provide

  13. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine.

    OpenAIRE

    Galea, E; Regunathan, S; Eliopoulos, V; Feinstein, D L; Reis, D J

    1996-01-01

    Agmatine, decarboxylated arginine, is a metabolic product of mammalian cells. Considering the close structural similarity between L-arginine and agmatine, we investigated the interaction of agmatine and nitric oxide synthases (NOSs), which use L-arginine to generate nitric oxide (NO) and citrulline. Brain, macrophages and endothelial cells were respectively used as sources for NOS isoforms I, II and III. Enzyme activity was measured by the production of nitrites or L-citrulline. Agmatine was ...

  14. Intrinsic electrical properties of mammalian neurons and CNS function: a historical perspective

    OpenAIRE

    Llinás, Rodolfo R.

    2014-01-01

    This brief review summarizes work done in mammalian neuroscience concerning the intrinsic electrophysiological properties of four neuronal types; Cerebellar Purkinje cells, inferior olivary cells, thalamic cells, and some cortical interneurons. It is a personal perspective addressing an interesting time in neuroscience when the reflex view of brain function, as the paradigm to understand global neuroscience, began to be modified towards one in which sensory input modulates rather than dictate...

  15. 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

  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. Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

    Directory of Open Access Journals (Sweden)

    Bodo C. Melnik

    2015-07-01

    Full Text Available Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1, the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1 essential branched-chain amino acids (BCAAs; (2 glutamine; (3 palmitic acid; and (4 bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER stress and drives an aimless quasi-program, which promotes aging and age-related diseases.

  18. Lutein, zeaxanthin and mammalian development: Metabolism, functions and implications for health.

    Science.gov (United States)

    Giordano, Elena; Quadro, Loredana

    2018-04-11

    It is now widely accepted that nutrition during critical periods in early development, both pre- and postnatal, may have lifetime consequences in determining health or onset of major diseases in the adult life. Dietary carotenoids have shown beneficial health effects throughout the life cycle due to their potential antioxidant properties, their ability to serves as precursors of vitamin A and to the emerging signaling functions of their metabolites. The non-provitamin A carotenoids lutein and zeaxanthin are emerging as important modulators of infant and child visual and cognitive development, as well as critical effectors in the prevention and treatment of morbidity associated with premature births. This review provides a general overview of lutein and zeaxanthin metabolism in mammalian tissues and highlights the major advancements and remaining gaps in knowledge in regards to their metabolism and health effects during pre- and early post-natal development. Furthering our knowledge in this area of research will impact dietary recommendation and supplementation strategies aimed at sustaining proper fetal and infant growth. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

    Science.gov (United States)

    Melnik, Bodo C.

    2015-01-01

    Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1) essential branched-chain amino acids (BCAAs); (2) glutamine; (3) palmitic acid; and (4) bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER) stress and drives an aimless quasi-program, which promotes aging and age-related diseases. PMID:26225961

  20. 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.

  1. 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...

  2. Surgical manipulation of mammalian embryos in vitro.

    Science.gov (United States)

    Naruse, I; Keino, H; Taniguchi, M

    1997-04-01

    Whole-embryo culture systems are useful in the fields of not only embryology but also teratology, toxicology, pharmacology, and physiology. Of the many advantages of whole-embryo culture, we focus here on the surgical manipulation of mammalian embryos. Whole-embryo culture allows us to manipulate mammalian embryos, similarly to fish, amphibian and avian embryos. Many surgical experiments have been performed in mammalian embryos in vitro. Such surgical manipulation alters the destiny of morphogenesis of the embryos and can answer many questions concerning developmental issues. As an example of surgical manipulation using whole-embryo culture systems, one of our experiments is described. Microsurgical electrocauterization of the deep preaxial mesodermal programmed cell death zone (fpp) in the footplate prevented the manifestation of polydactyly in genetic polydactyly mouse embryos (Pdn/Pdn), in which fpp was abolished.

  3. Mammalian diversity: gametes, embryos and reproduction.

    Science.gov (United States)

    Behringer, Richard R; Eakin, Guy S; Renfree, Marilyn B

    2006-01-01

    The class Mammalia is composed of approximately 4800 extant species. These mammalian species are divided into three subclasses that include the monotremes, marsupials and eutherians. Monotremes are remarkable because these mammals are born from eggs laid outside of the mother's body. Marsupial mammals have relatively short gestation periods and give birth to highly altricial young that continue a significant amount of 'fetal' development after birth, supported by a highly sophisticated lactation. Less than 10% of mammalian species are monotremes or marsupials, so the great majority of mammals are grouped into the subclass Eutheria, including mouse and human. Mammals exhibit great variety in morphology, physiology and reproduction. In the present article, we highlight some of this remarkable diversity relative to the mouse, one of the most widely used mammalian model organisms, and human. This diversity creates challenges and opportunities for gamete and embryo collection, culture and transfer technologies.

  4. Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth

    Directory of Open Access Journals (Sweden)

    Pujiao Yu

    2016-01-01

    Full Text Available The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs, as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs—miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p—were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

  5. Deep sequencing analysis of the developing mouse brain reveals a novel microRNA

    Directory of Open Access Journals (Sweden)

    Piltz Sandra

    2011-04-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are small non-coding RNAs that can exert multilevel inhibition/repression at a post-transcriptional or protein synthesis level during disease or development. Characterisation of miRNAs in adult mammalian brains by deep sequencing has been reported previously. However, to date, no small RNA profiling of the developing brain has been undertaken using this method. We have performed deep sequencing and small RNA analysis of a developing (E15.5 mouse brain. Results We identified the expression of 294 known miRNAs in the E15.5 developing mouse brain, which were mostly represented by let-7 family and other brain-specific miRNAs such as miR-9 and miR-124. We also discovered 4 putative 22-23 nt miRNAs: mm_br_e15_1181, mm_br_e15_279920, mm_br_e15_96719 and mm_br_e15_294354 each with a 70-76 nt predicted pre-miRNA. We validated the 4 putative miRNAs and further characterised one of them, mm_br_e15_1181, throughout embryogenesis. Mm_br_e15_1181 biogenesis was Dicer1-dependent and was expressed in E3.5 blastocysts and E7 whole embryos. Embryo-wide expression patterns were observed at E9.5 and E11.5 followed by a near complete loss of expression by E13.5, with expression restricted to a specialised layer of cells within the developing and early postnatal brain. Mm_br_e15_1181 was upregulated during neurodifferentiation of P19 teratocarcinoma cells. This novel miRNA has been identified as miR-3099. Conclusions We have generated and analysed the first deep sequencing dataset of small RNA sequences of the developing mouse brain. The analysis revealed a novel miRNA, miR-3099, with potential regulatory effects on early embryogenesis, and involvement in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development.

  6. Congenital salivary gland anlage tumor - in utero and postnatal imaging

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishnan, Rupa; Calvo-Garcia, Maria A.; Koch, Bernadette L. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Lim, Foong-Yen [Cincinnati Children' s Hospital Medical Center, Division of Pediatric Surgery, Cincinnati, OH (United States); Elluru, Ravindhra G. [Cincinnati Children' s Hospital Medical Center, Division of Pediatric Otolaryngology, Cincinnati, OH (United States)

    2015-03-01

    We present a case of an infant with congenital salivary gland anlage tumor, with fetal and postnatal imaging. To the best of our knowledge, this is the first case describing the in utero imaging findings of salivary gland anlage tumor. A fetal MRI was performed secondary to the clinical finding of polyhydramnios, which identified a nasopharyngeal mass. Because findings were concerning for airway obstruction, the fetus was delivered by ex utero intrapartum treatment (EXIT) to airway procedure. A postnatal CT confirmed the findings of the fetal MRI. The lesion was resected when the baby was 4 days old and recovery was uneventful. (orig.)

  7. [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.

  8. Acoustophoretic Synchronization of Mammalian Cells in Microchannels

    DEFF Research Database (Denmark)

    Thévoz, P.; Adams, J.D.; Shea, H.

    2010-01-01

    We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel to selec......We report the first use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. The acoustophoretic cell synchronization (ACS) device utilizes volume-dependent acoustic radiation force within a microchannel...

  9. DNA repair in non-mammalian animals

    International Nuclear Information System (INIS)

    Mitani, Hiroshi

    1984-01-01

    Studies on DNA repair have been performed using microorganisms such as Escherichia coli and cultured human and mammalian cells. However, it is well known that cultured organic cells differ from each other in many respects, although DNA repair is an extremely fundamental function of organisms to protect genetic information from environmental mutagens such as radiation and 0 radicals developing in the living body. To answer the question of how DNA repair is different between the animal species, current studies on DNA repair of cultured vertebrate cells using the methods similar to those in mammalian experiments are reviewed. (Namekawa, K.)

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum.

    Science.gov (United States)

    McDougall, Annie R A; Wiradjaja, Vanny; Azhan, Aminath; Li, Anqi; Hale, Nadia; Wlodek, Mary E; Hooper, Stuart B; Wallace, Megan J; Tolcos, Mary

    2017-01-01

    Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0.05) compared with controls. At P7, the width of the external granule layer (EGL) was 30% greater in IUGR than control rats (p < 0.05); there was no difference in the width of the proliferative zone or in the density of Ki67-positive cells in the EGL. Bergmann glia were disorganized at P7 and P35 in IUGR pups, and by P35, there was a 10% decrease in Bergmann glial fiber density (p < 0.05) compared with controls. At P7, trophoblast antigen-2 (Trop2) mRNA and protein levels in the cerebellum were decreased by 88 and 40%, respectively, and astrotactin 1 mRNA levels were increased by 20% in the IUGR rats (p < 0.05) compared with controls; there was no difference in ASTN1 protein. The expressions of other factors known to regulate cerebellar development (astrotactin 2, brain-derived neurotrophic factor, erb-b2 receptor tyrosine kinase 4, neuregulin 1, sonic hedgehog and somatostatin) were not different between IUGR and control rats at P7 or P35. These data suggest that damage to the migratory scaffold (Bergmann glial fibers) and alterations in the genes that influence migration (Trop2 and Astn1) may underlie the deficits in postnatal cerebellar development following IUGR. © 2017 S. Karger AG, Basel.

  13. Dopamine receptor and Gα(olf expression in DYT1 dystonia mouse models during postnatal development.

    Directory of Open Access Journals (Sweden)

    Lin Zhang

    Full Text Available DYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (ΔGAG in the DYT1 gene. Neuroimaging studies and studies using mouse models suggest that DYT1 dystonia is associated with dopamine imbalance. However, whether dopamine imbalance is key to DYT1 or other forms of dystonia continues to be debated.We used Dyt1 knock out (Dyt1 KO, Dyt1 ΔGAG knock-in (Dyt1 KI, and transgenic mice carrying one copy of the human DYT1 wild type allele (DYT1 hWT or human ΔGAG mutant allele (DYT1 hMT. D1R, D2R, and Gα(olf protein expression was analyzed by western blot in the frontal cortex, caudate-putamen and ventral midbrain in young adult (postnatal day 60; P60 male mice from all four lines; and in the frontal cortex and caudate putamen in juvenile (postnatal day 14; P14 male mice from the Dyt1 KI and KO lines. Dopamine receptor and Gα(olf protein expression were significantly decreased in multiple brain regions of Dyt1 KI and Dyt1 KO mice and not significantly altered in the DYT1 hMT or DYT1 hWT mice at P60. The only significant change at P14 was a decrease in D1R expression in the caudate-putamen of the Dyt1 KO mice.We found significant decreases in key proteins in the dopaminergic system in multiple brain regions of Dyt1 KO and Dyt1 KI mouse lines at P60. Deletion of one copy of the Dyt1 gene (KO mice produced the most pronounced effects. These data offer evidence that impaired dopamine receptor signaling may be an early and significant contributor to DYT1 dystonia pathophysiology.

  14. Generation of induced neurons by direct reprogramming in the mammalian cochlea.

    Science.gov (United States)

    Nishimura, K; Weichert, R M; Liu, W; Davis, R L; Dabdoub, A

    2014-09-05

    Primary auditory neurons (ANs) in the mammalian cochlea play a critical role in hearing as they transmit auditory information in the form of electrical signals from mechanosensory cochlear hair cells in the inner ear to the brainstem. Their progressive degeneration is associated with disease conditions, excessive noise exposure and aging. Replacement of ANs, which lack the ability to regenerate spontaneously, would have a significant impact on research and advancement in cochlear implants in addition to the amelioration of hearing impairment. The aim of this study was to induce a neuronal phenotype in endogenous non-neural cells in the cochlea, which is the essential organ of hearing. Overexpression of a neurogenic basic helix-loop-helix transcription factor, Ascl1, in the cochlear non-sensory epithelial cells induced neurons at high efficiency at embryonic, postnatal and juvenile stages. Moreover, induced neurons showed typical properties of neuron morphology, gene expression and electrophysiology. Our data indicate that Ascl1 alone or Ascl1 and NeuroD1 is sufficient to reprogram cochlear non-sensory epithelial cells into functional neurons. Generation of neurons from non-neural cells in the cochlea is an important step for the regeneration of ANs in the mature mammalian cochlea. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Localización de los Receptores Cannabinoides 1 (CB1) en Glándulas Salivales Submandibulares y Sublinguales de Ratones Durante el Desarrollo Postnatal

    OpenAIRE

    Hipkaeo, Wiphawi; Watanabe, Masahiko; Kondo, Hisatake

    2015-01-01

    In view of the fact that human marijuana users often show dry mouth symptom, the present study was attempted to examine the localization of CB1, which was originally identified in brain, in the submandibular and sublingual salivary glands of postnatal developing male mice by immunohistochemistry. In submandibular gland, CB1-immunoreactivity was positive in a majority of acinar cells in forms of granular appearance in their apical cytoplasm, while it was negative in the ducts at newborn stage....

  16. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R

    2014-03-26

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  17. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    Objectives: To review the research findings on the expression of endogenous retroviruses and retroviral-related particles in male mammalian reproductive tissues, and to discuss their possible role in normal cellular events and association with disease conditions in male reproductive tissues. Data sources: Published ...

  18. Locomotor circuits in the mammalian spinal cord

    DEFF Research Database (Denmark)

    Kiehn, Ole

    2006-01-01

    Intrinsic spinal networks, known as central pattern generators (CPGs), control the timing and pattern of the muscle activity underlying locomotion in mammals. This review discusses new advances in understanding the mammalian CPGs with a focus on experiments that address the overall network struct...

  19. A promoter-level mammalian expression atlas

    KAUST Repository

    Forest, Alistair R R; Kawaji, Hideya; Rehli, Michael; Baillie, John Kenneth; De Hoon, Michiel Jl L; Haberle, Vanja; Lassmann, Timo; Kulakovskiy, Ivan V.; Lizio, Marina; Itoh, Masayoshi; Andersson, Robin; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R.; Jia, Hui; Joshi, Anagha Madhusudan; Jurman, Giuseppe; Kaczkowski, Bogumił; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Mungall, Christopher J.; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Kasianov, Artem S.; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawashima, Tsugumi; Meehan, Terrence F.; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klinken, Svend Peter; Knox, Alan; Kojima, Miki; Kojima, Soichi; Kondo, Naoto; Schmeier, Sebastian; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T.; Laros, Jeroen F J; Lee, Weonju; Lennartsson, Andreas; Li, Kang; Lilje, Berit; Bertin, Nicolas; Lipovich, Leonard; MacKay-Sim, Alan; Manabe, Riichiroh; Mar, Jessica; Marchand, Benoî t; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison M.; Mizuno, Yosuke; De Morais, David A Lima; Jø rgensen, Mette Christine; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L.; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakachi, Yutaka; Nakahara, Fumio; Dimont, Emmanuel; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; Van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Arner, Erik; Ohmiya, Hiroko; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Pain, Arnab; Passier, Robert C J J; Patrikakis, Margaret; Schmidl, Christian; Persson, Helena A.; Piazza, Silvano; Prendergast, James G D; Rackham, Owen J L; Ramilowski, Jordan A.; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Schaefer, Ulf; Rye, Morten Beck; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Medvedeva, Yulia; Schneider, Claudio H.; Schultes, Erik A.; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W.; Simon, Chris M.; Plessy, Charles; Sugiyama, Daisuke; Sugiyama, Takaaki; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K.; 't Hoen, Peter Ac Chr; Tagami, Michihira; Tagami, Naokotakahashi; Takai, Jun; Tanaka, Hiroshi; Vitezic, Morana; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyoda, Hiroo; Toyoda, Tetsuro; Valen, Eivind; Van De Wetering, Marc L.; Van Den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Severin, Jessica M.; Vorontsov, Ilya E.; Wasserman, Wyeth W.; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise Natalie; Wolvetang, Ernst Jurgen; Wood, Emily J.; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Semple, Colin Am M; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Susan E.; Zhang, Peter; Zhao, Xiaobei; Zucchelli, Silvia; Summers, Kim M.; Suzuki, Harukazu; Daub, Carsten Olivier; Kawai, Jun; Ishizu, Yuri; Heutink, Peter; Hide, Winston; Freeman, Tom C.; Lenhard, Boris; Bajic, Vladimir B.; Taylor, Martin S.; Makeev, Vsevolod J.; Sandelin, Albin; Hume, David A.; Carninci, Piero; Young, Robert S.; Hayashizaki, Yoshihide Yoshihide; Francescatto, Margherita; Altschuler, Intikhab Alam; Albanese, Davide; Altschule, Gabriel M.; Arakawa, Takahiro; Archer, John A.C.; Arner, Peter; Babina, Magda; Rennie, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan-Bhatt, Swati; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James A.; Brombacher, Frank; Burroughs, Alexander Maxwell; Califano, Andrea C.; Cannistraci, Carlo; Carbajo, Daniel; Chen, Yun; Chierici, Marco; Ciani, Yari; Clevers, Hans C.; Dalla, Emiliano; Davis, Carrie Anne; Detmar, Michael J.; Diehl, Alexander D.; Dohi, Taeko; Drablø s, Finn; Edge, Albert SB B; Edinger, Matthias G.; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey R.; Fang, Hai; Farach-Carson, Mary Cindy; Faulkner, Geoffrey J.; Favorov, Alexander V.; Fisher, Malcolm E.; Frith, Martin C.; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Junichi; Geijtenbeek, Teunis Bh H; Gibson, Andrew P.; Gingeras, Thomas R.; Goldowitz, Dan; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard F.; Hitchens, Kelly J.; Sui, Shannan J Ho; Hofmann, Oliver M.; Hoof, Ilka; Hori, Fumi; Huminiecki, Łukasz B.

    2014-01-01

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

  20. Structure and function of mammalian cilia

    DEFF Research Database (Denmark)

    Satir, Peter; Christensen, Søren T

    2008-01-01

    In the past half century, beginning with electron microscopic studies of 9 + 2 motile and 9 + 0 primary cilia, novel insights have been obtained regarding the structure and function of mammalian cilia. All cilia can now be viewed as sensory cellular antennae that coordinate a large number...

  1. Archetype, adaptation and the mammalian heart

    NARCIS (Netherlands)

    Meijler, F.L.; Meijler, T.D.

    2011-01-01

    Forty years ago, we started our quest for 'The Holy Grail' of understanding ventricular rate control and rhythm in atrial fibrillation (AF). We therefore studied the morphology and function of a wide range of mammalian hearts. From mouse to whale, we found that all hearts show similar structural

  2. A survey of pregnant and postnatal women, clinic attendees and ...

    African Journals Online (AJOL)

    A survey of pregnant and postnatal women, clinic attendees and maternity staff regarding the presence of birth companions during labour and delivery. ... Conclusion: The involvement of birth companions supporting women during childbirth could be promoted as a low cost preventive intervention to improve maternal and ...

  3. Equine locomotory muscles : postnatal development and the influence of exercise

    NARCIS (Netherlands)

    Dingboom, Elizabeth Gerardina

    2002-01-01

    The Dutch warmblood horse is widely used in different types of sport. The individual capacity to perform depends on factors as character and the quality of the cardiopulmonary and musculoskeletal system. These factors are partly genetically determined; in the postnatal phase of growth and maturation

  4. Prenatal, perinatal and postnatal factors associated with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Imen Hadjkacem

    2016-11-01

    Conclusions: The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others, as determinant variables for the genesis of ASD.

  5. 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,

  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. Postnatal depression - an examination of psychosocial factors | Mills ...

    African Journals Online (AJOL)

    Postnatal depression (PND) has been underreported in South Africa. This retrospective study investigated factors which appear to predispose women to PND. Two groups, one consisting of women who suffered from PND and the other of women free of this complaint, provided information on a number of biological, ...

  8. Postnatal morphology of hematoencephalic barrier in hypoxic lesion

    Directory of Open Access Journals (Sweden)

    E. V. Kikhtenko

    2012-12-01

    Full Text Available In infants with perinatal hypoxic lesion of the central nervous system swelling and death of the endothelium, thickening of the capillary basement membranes, karyorrhexis and plasmorrhexis of astrocytes are observed. The severity and degree of pathological changes depends on the time of hypoxic exposure (antenatal or intrapartum period and the term of postnatal life.

  9. Postnatal cranial ultrasonographic findings in feto-fetal transfusion syndrome.

    NARCIS (Netherlands)

    Breysem, L.; Naulaers, G.; Deprest, J.; Schoubroeck, D.V.; Daniels, H.; Lammens, M.M.Y.; Smet, M.H.

    2002-01-01

    Our objective was a retrospective evaluation of cranial US in survivors of twin pregnancy with feto-fetal transfusion syndrome (FFTS), with knowledge of prenatal treatment and neonatal/postnatal clinical data. In 18 pregnancies with FFTS (January 1996 to May 2000), pregnancy management and outcome,

  10. Postnatal Growth Rates of Hummingbirds : Review and New Records

    NARCIS (Netherlands)

    Freymann, Bernd P.; Schuchmann, Karl-Ludwig

    2008-01-01

    We review the published information on postnatal growth rates of hummingbirds (13 species), and report previously unpublished records for nine additional trochilid species. The allometric relationship based on the log(10)-transformed data of K (logistic growth rate constant) and body mass has a

  11. An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain.

    Science.gov (United States)

    Kang, Jongkyun; Shin, Sarah; Perrimon, Norbert; Shen, Jie

    2017-07-01

    Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease. Presenilin and Nicastrin are essential components of γ-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins. Genetic studies in mice previously demonstrated that conditional inactivation of Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The roles of Drosophila Presenilin ( Psn ) and Nicastrin ( Nct ) in the adult fly brain, however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality-a phenotype that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore, expression of these shRNAs in the wing disc caused notching wing phenotypes, which are also shared with Psn and Nct mutants. Similar to Nct , neuron-specific Psn KD using two independent shRNA lines led to early mortality and rough eye phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4 and tubulin-Gal80 ts system caused shortened lifespan, climbing defects, increases in apoptosis, and age-dependent neurodegeneration. Together, these findings demonstrate that, similar to their mammalian counterparts, Drosophila Psn and Nct are required for neuronal survival during aging and normal lifespan, highlighting an evolutionarily conserved role of Presenilin in neuronal protection in the aging brain. Copyright © 2017 by the Genetics Society of America.

  12. Prenatal family support, postnatal family support and postpartum depression.

    Science.gov (United States)

    Xie, Ri-Hua; Yang, Jianzhou; Liao, Shunping; Xie, Haiyan; Walker, Mark; Wen, Shi Wu

    2010-08-01

    Inadequate social support is an important determinant of postpartum depression (PPD). Social support for pregnant women consists of supports from various sources and can be measured at different gestation periods. Differentiating the effects of social support from different sources and measured at different gestation periods may have important implications in the prevention of PPD. In the family centred Chinese culture, family support is likely to be one of the most important components in social support. The aim of this study was to assess the association of prenatal family support and postnatal family support with PPD. A prospective cohort study was conducted between February and September 2007 in Hunan, China. Family support was measured with social support rating scale at 30-32 weeks of gestation (prenatal support) and again at 2 weeks of postpartum visit (postnatal support). PPD was defined as Edinburgh Postnatal Depression Scale (EPDS) score > or =13. A total of 534 pregnant women were included, and among them, 103 (19.3%) scored 13 or more on the EPDS. PPD was 19.4% in the lowest tertile versus 18.4% in the highest quartile (adjusted odds ratio: 1.04, 95% confidence interval 0.60, 1.80) for prenatal support from all family members, and PPD was 39.8% in the lowest tertile versus 9.6% in the highest tertile (adjusted odds ratio: 4.4, 95% confidence interval 2.3, 8.4) for postnatal support from all family members. Among family members, support from husband had the largest impact on the risk of developing PPD. Lack of postnatal family support, especially the support from husband, is an important risk factor of PPD.

  13. 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

  14. Prenatal, perinatal and postnatal factors associated with autism spectrum disorder.

    Science.gov (United States)

    Hadjkacem, Imen; Ayadi, Héla; Turki, Mariem; Yaich, Sourour; Khemekhem, Khaoula; Walha, Adel; Cherif, Leila; Moalla, Yousr; Ghribi, Farhat

    To identify prenatal, perinatal and postnatal risk factors in children with autism spectrum disorder (ASD) by comparing them to their siblings without autistic disorders. The present study is cross sectional and comparative. It was conducted over a period of three months (July-September 2014). It included 101 children: 50 ASD's children diagnosed according to DSM-5 criteria and 51 unaffected siblings. The severity of ASD was assessed by the CARS. Our study revealed a higher prevalence of prenatal, perinatal and postnatal factors in children with ASD in comparison with unaffected siblings. It showed also a significant association between perinatal and postnatal factors and ASD (respectively p=0.03 and p=0.042). In this group, perinatal factors were mainly as type of suffering acute fetal (26% of cases), long duration of delivery and prematurity (18% of cases for each factor), while postnatal factors were represented principally by respiratory infections (24%). As for parental factors, no correlation was found between advanced age of parents at the moment of the conception and ASD. Likewise, no correlation was observed between the severity of ASD and different factors. After logistic regression, the risk factors retained for autism in the final model were: male gender, prenatal urinary tract infection, acute fetal distress, difficult labor and respiratory infection. The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others), as determinant variables for the genesis of ASD. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  15. Prenatal, perinatal and postnatal factors associated with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Imen Hadjkacem

    Full Text Available Abstract Objective: To identify prenatal, perinatal and postnatal risk factors in children with autism spectrum disorder (ASD by comparing them to their siblings without autistic disorders. Method: The present study is cross sectional and comparative. It was conducted over a period of three months (July-September 2014. It included 101 children: 50 ASD's children diagnosed according to DSM-5 criteria and 51 unaffected siblings. The severity of ASD was assessed by the CARS. Results: Our study revealed a higher prevalence of prenatal, perinatal and postnatal factors in children with ASD in comparison with unaffected siblings. It showed also a significant association between perinatal and postnatal factors and ASD (respectively p = 0.03 and p = 0.042. In this group, perinatal factors were mainly as type of suffering acute fetal (26% of cases, long duration of delivery and prematurity (18% of cases for each factor, while postnatal factors were represented principally by respiratory infections (24%. As for parental factors, no correlation was found between advanced age of parents at the moment of the conception and ASD. Likewise, no correlation was observed between the severity of ASD and different factors. After logistic regression, the risk factors retained for autism in the final model were: male gender, prenatal urinary tract infection, acute fetal distress, difficult labor and respiratory infection. Conclusions: The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others, as determinant variables for the genesis of ASD.

  16. Pattern and density of vascularization in mammalian testes, ovaries, and ovotestes.

    Science.gov (United States)

    Lupiáñez, Darío G; Real, Francisca M; Dadhich, Rajesh K; Carmona, Francisco D; Burgos, Miguel; Barrionuevo, Francisco J; Jiménez, Rafael

    2012-05-01

    According to the classical paradigm, the vasculature of the embryonic testis is more dense and complex than that of the ovary, but recent studies based on whole-mount detection of Caveolin-1 (CAV1) as an endothelial cell marker, have suggested that the level of ovarian vascularization is higher than previously assumed. However, this new hypothesis has been neither tested using alternative methodology nor investigated in other mammalian species. In this paper, we have studied the vascularization process in the gonads of males and females of two mammalian species, the mouse (Mus musculus) and the Iberian mole (Talpa occidentalis). Our results show that the pattern of testis vascularization is very well conserved among mammals, including both pre- and postnatal stages of development and, at least in the mole, it is conserved irrespectively of whether the testicular tissue is XY or XX. We have shown that CAV1 is present not only in endothelial cells but also in prefollicular oocytes and in an ovarian population of somatic cortical cells. These data clearly establish that: (1) according to the classical hypothesis, the degree of vascularization of the developing ovary is lower than that of the testis, (2) ovarian vascularization is also evolutionarily conserved as it occurs similarly both in moles and in mice, and (3) that the degree of vascular development of the mammalian ovary is age-dependent increasing significatively at puberty. The expression of CAV1 in the ovary of most animal taxa, from nematodes to mammals, strongly suggests a role for this gene in the female meiosis. © 2012 WILEY PERIODICALS, INC.

  17. 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.

  18. Predictors of intelligence at the age of 5: family, pregnancy and birth characteristics, postnatal influences, and postnatal growth.

    Directory of Open Access Journals (Sweden)

    Hanne-Lise Falgreen Eriksen

    Full Text Available 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.

  19. Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish.

    Science.gov (United States)

    Monteiro, Diana A; Taylor, Edwin W; Sartori, Marina R; Cruz, André L; Rantin, Francisco T; Leite, Cleo A C

    2018-02-01

    The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems.

  20. Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish

    Science.gov (United States)

    Monteiro, Diana A.; Taylor, Edwin W.; Sartori, Marina R.; Cruz, André L.; Rantin, Francisco T.; Leite, Cleo A. C.

    2018-01-01

    The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems. PMID:29507882

  1. Trib3 is developmentally and nutritionally regulated in the brain but is dispensable for spatial memory, fear conditioning and sensing of amino acid-imbalanced diet.

    Directory of Open Access Journals (Sweden)

    Tiit Örd

    Full Text Available Tribbles homolog 3 (TRIB3 is a mammalian pseudokinase that is induced in neuronal cell cultures in response to cell death-inducing stresses, including neurotrophic factor deprivation. TRIB3 is an inhibitor of activating transcription factor 4 (ATF4, the central transcriptional regulator in the eukaryotic translation initiation factor 2α (eIF2α phosphorylation pathway that is involved in the cellular stress response and behavioral processes. In this article, we study the expression of Trib3 in the mouse brain, characterize the brain morphology of mice with a genetic ablation of Trib3 and investigate whether Trib3 deficiency alters eIF2α-dependent cognitive abilities. Our data show that the consumption of a leucine-deficient diet induces Trib3 expression in the anterior piriform cortex, the brain region responsible for detecting essential amino acid intake imbalance. However, the aversive response to leucine-devoid diet does not differ in Trib3 knockout and wild type mice. Trib3 deletion also does not affect long-term spatial memory and reversal learning in the Morris water maze and auditory or contextual fear conditioning. During embryonic development, Trib3 expression increases in the brain and persists in the early postnatal stadium. Neuroanatomical characterization of mice lacking Trib3 revealed enlarged lateral ventricles. Thus, although the absence of Trib3 does not alter the eIF2α pathway-dependent cognitive functions of several areas of the brain, including the hippocampus, amygdala and anterior piriform cortex, Trib3 may serve a role in other central nervous system processes and molecular pathways.

  2. Trib3 is developmentally and nutritionally regulated in the brain but is dispensable for spatial memory, fear conditioning and sensing of amino acid-imbalanced diet.

    Science.gov (United States)

    Örd, Tiit; Innos, Jürgen; Lilleväli, Kersti; Tekko, Triin; Sütt, Silva; Örd, Daima; Kõks, Sulev; Vasar, Eero; Örd, Tõnis

    2014-01-01

    Tribbles homolog 3 (TRIB3) is a mammalian pseudokinase that is induced in neuronal cell cultures in response to cell death-inducing stresses, including neurotrophic factor deprivation. TRIB3 is an inhibitor of activating transcription factor 4 (ATF4), the central transcriptional regulator in the eukaryotic translation initiation factor 2α (eIF2α) phosphorylation pathway that is involved in the cellular stress response and behavioral processes. In this article, we study the expression of Trib3 in the mouse brain, characterize the brain morphology of mice with a genetic ablation of Trib3 and investigate whether Trib3 deficiency alters eIF2α-dependent cognitive abilities. Our data show that the consumption of a leucine-deficient diet induces Trib3 expression in the anterior piriform cortex, the brain region responsible for detecting essential amino acid intake imbalance. However, the aversive response to leucine-devoid diet does not differ in Trib3 knockout and wild type mice. Trib3 deletion also does not affect long-term spatial memory and reversal learning in the Morris water maze and auditory or contextual fear conditioning. During embryonic development, Trib3 expression increases in the brain and persists in the early postnatal stadium. Neuroanatomical characterization of mice lacking Trib3 revealed enlarged lateral ventricles. Thus, although the absence of Trib3 does not alter the eIF2α pathway-dependent cognitive functions of several areas of the brain, including the hippocampus, amygdala and anterior piriform cortex, Trib3 may serve a role in other central nervous system processes and molecular pathways.

  3. Developmental and behavioral effects of postnatal amitraz exposure in rats

    Directory of Open Access Journals (Sweden)

    J. Palermo-Neto

    1997-08-01

    Full Text Available The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/kg orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg on the same days. A total of 18 different litters (9 of them control and 9 experimental born after a 21-day gestation were used. The results showed that the median effective time (ET50 for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively. The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds to perform the surface righting reflex on postnatal days (PND 3 (25.0 ± 2.0, 4 (12.3 ± 1.2 and 5 (8.7 ± 0.9 in relation to controls (10.6 ± 1.2; 4.5 ± 0.6 and 3.4 ± 0.4, respectively; the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140 ± 11 and 17 (124 ± 12, and 16 (104 ± 9, 17 (137 ± 9 and 18 (106 ± 8, respectively. Data on spontaneous motor activity of the control male and female pups were 59 ± 11 and 69 ± 10 for days 16 and 17 and 49 ± 9, 48 ± 7 and 56 ± 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz-treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate

  4. Sugar for the brain: the role of glucose in physiological and pathological brain function.

    Science.gov (United States)

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

    2013-10-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Mammalian Sperm Motility: Observation and Theory

    KAUST Repository

    Gaffney, E.A.

    2011-01-21

    Mammalian spermatozoa motility is a subject of growing importance because of rising human infertility and the possibility of improving animal breeding. We highlight opportunities for fluid and continuum dynamics to provide novel insights concerning the mechanics of these specialized cells, especially during their remarkable journey to the egg. The biological structure of the motile sperm appendage, the flagellum, is described and placed in the context of the mechanics underlying the migration of mammalian sperm through the numerous environments of the female reproductive tract. This process demands certain specific changes to flagellar movement and motility for which further mechanical insight would be valuable, although this requires improved modeling capabilities, particularly to increase our understanding of sperm progression in vivo. We summarize current theoretical studies, highlighting the synergistic combination of imaging and theory in exploring sperm motility, and discuss the challenges for future observational and theoretical studies in understanding the underlying mechanics. © 2011 by Annual Reviews. All rights reserved.

  6. Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

    International Nuclear Information System (INIS)

    Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

    2016-01-01

    The presence of 137 Cesium ( 137 Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137 Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l −1 ) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137 Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation.

  7. Late effects of in utero exposure to carcinogens in rats, with special reference to postnatal growth and tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Naito, Y; Takizawa, S; Watanabe, H; Hirose, F [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1976-11-01

    Fifteen-day pregnant Wistar/Furth rats were irradiated with 100 rads of x ray of fast neutron (14.1 MeV). Fast neutron was found to be more effective than x rays in reducing the number of live-births and in retarding the postnatal growth of the offspring. Among the various organs examined, the brain, uterus, spleen and gonads were highly radiosensitive in terms of organ weight. Microscopic examination revealed a marked dysplasia of the ovary in the fast neutron-irradiated rats. Pre-conception irradiation did not cause any deleterious effects on the offspring. No substantial difference was noted in the peripheral blood pictures or on the tumor incidence in rats born from the irradiated female rats. On the other hand, it was noteworthy that N-butylnitrosourea given transplacentally induced 3 cases of brain tumor. The incidence of leukemia and mammary tumor was significantly higher in the irradiated or carcinogen-treated pregnant rats.

  8. Radiation effects in mammalian cells in vitro

    International Nuclear Information System (INIS)

    Hill, C.K.; Han, A.; Elkind, M.M.; Wells, R.L.; Buess, E.M.; Lin, C.M.

    1985-01-01

    The purpose of this research effort is to elucidate the mechanisms for the radiation-induced changes in mammalian cells that lead to cell death, mutation, neoplastic transformation, DNA damage, and chromosomal alterations. Of particular interest are the effects of low-dose-rate and fractionated irradiation on these end points with respect to the mechanisms whereby these effects are influenced by cellular repair processes, inhibitors, and promoters that act at the genetic or biochemical level. 17 refs

  9. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

    Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

    2017-06-21

    The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

  10. Comparison of amphibian and mammalian thyroperoxidase ...

    Science.gov (United States)

    Thyroperoxidase (TPO) catalyzes the production of thyroid hormones in the vertebrate thyroid gland by oxidizing iodide (I- ) to produce iodinated tyrosines on thyroglobulin, and further coupling of specific mono- or di-iodinated tyrosines to generate the triiodo- and tetra-iodothyronine, precursors to thyroid hormone. This enzyme is a target for thyroid disrupting chemicals. TPO-inhibition by xenobiotics is a molecular initiating event that is known to perturb the thyroid axis by preventing synthesis of thyroid hormone. Previous work on TPO-inhibition has been focused on mammalian TPO; specifically, the rat and pig. A primary objective of this experiment was to directly measure TPO activity in a non-mammalian system, in this case a thyroid gland homogenate from Xenopus laevis; as well as compare chemical inhibition from past mammalian studies to the amphibian data generated. Thyroid glands obtained from X. laevis tadpoles at NF stages 58-60, were pooled and homogenized by sonication in phosphate buffer. This homogenate was then used to test 24 chemicals for inhibition of TPO as measured by conversion of Amplex UltraRed (AUR) substrate to its fluorescent product. The test chemicals were selected based upon previous results from rat in vitro TPO assays, and X. laevis in vitro and in vivo studies for thyroid disrupting endpoints, and included both positive and negative chemicals in these assays. An initial screening of the chemicals was done at a single high con

  11. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung, E-mail: keejung@skku.edu

    2015-02-27

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics.

  12. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

    International Nuclear Information System (INIS)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung

    2015-01-01

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics

  13. The Endocannabinoid System across Postnatal Development in Transmembrane Domain Neuregulin 1 Mutant Mice

    Directory of Open Access Journals (Sweden)

    Rose Chesworth

    2018-02-01

    Full Text Available The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether molecular alterations exist in the endocannabinoid signalling pathway during brain development in a mouse model for the schizophrenia risk gene neuregulin 1 (Nrg1. We analysed transcripts encoding key molecules of the endocannabinoid system in heterozygous transmembrane domain Nrg1 mutant mice (Nrg1 TM HET, which is known to have increased sensitivity to cannabis exposure. Tissue from the prelimbic cortex and hippocampus of male and female Nrg1 TM HET mice and wild type-like littermates was collected at postnatal days (PNDs 7, 10, 14, 21, 28, 35, 49, and 161. Quantitative polymerase chain reaction was conducted to assess mRNA levels of cannabinoid receptor 1 (CB1R and enzymes for the synthesis and breakdown of the endocannabinoid 2-arachidonoylglycerol [i.e., diacylglycerol lipase alpha (DAGLα, monoglyceride lipase (MGLL, and α/β-hydrolase domain-containing 6 (ABHD6]. No sex differences were found for any transcripts in either brain region; thus, male and female data were pooled. Hippocampal and cortical mRNA expression of DAGLα, MGLL, and ABHD6 increased until PND 21–35 and then decreased and stabilised for the rest of postnatal development. Hippocampal CB1R mRNA expression increased until PND 21 and decreased after this age. Expression levels of these endocannabinoid markers did not differ in Nrg1 TM HET compared to control mice at any time point. Here, we demonstrate dynamic changes in the developmental trajectory of several key endocannabinoid system transcripts in the mouse brain, which may correspond with periods of endocannabinoid system maturation. Nrg1 TM HET mutation did not alter the developmental trajectory of the

  14. Prenatal and postnatal evaluation of polymicrogyria with band heterotopia.

    Science.gov (United States)

    Nagaraj, Usha D; Hopkin, Robert; Schapiro, Mark; Kline-Fath, Beth

    2017-09-01

    The coexistence of band heterotopia and polymicrogyria is extremely rare though it has been reported in the presence of corpus callosum anomalies and megalencephaly. We present prenatal and postnatal MRI findings of a rare case of diffuse cortical malformation characterized by polymicrogyria and band heterotopia. Agenesis of the corpus callosum and megalencephaly were also noted. In addition, bilateral closed-lip schizencephaly was identified on postnatal MRI, which has not been previously reported with this combination of imaging findings. Polymicrogyria with band heterotopia can occur and can be diagnosed with fetal MRI. The coexistence of corpus callosum anomalies and megalencephaly comprises a rare phenotype that has been previously described, suggesting an underlying genetic abnormality.

  15. Prenatal and postnatal evaluation of polymicrogyria with band heterotopia

    Directory of Open Access Journals (Sweden)

    Usha D. Nagaraj, MD

    2017-09-01

    Full Text Available The coexistence of band heterotopia and polymicrogyria is extremely rare though it has been reported in the presence of corpus callosum anomalies and megalencephaly. We present prenatal and postnatal MRI findings of a rare case of diffuse cortical malformation characterized by polymicrogyria and band heterotopia. Agenesis of the corpus callosum and megalencephaly were also noted. In addition, bilateral closed-lip schizencephaly was identified on postnatal MRI, which has not been previously reported with this combination of imaging findings. Polymicrogyria with band heterotopia can occur and can be diagnosed with fetal MRI. The coexistence of corpus callosum anomalies and megalencephaly comprises a rare phenotype that has been previously described, suggesting an underlying genetic abnormality.

  16. Long-Lasting Crossmodal Cortical Reorganization Triggered by Brief Postnatal Visual Deprivation.

    Science.gov (United States)

    Collignon, Olivier; Dormal, Giulia; de Heering, Adelaide; Lepore, Franco; Lewis, Terri L; Maurer, Daphne

    2015-09-21

    Animal and human studies have demonstrated that transient visual deprivation early in life, even for a very short period, permanently alters the response properties of neurons in the visual cortex and leads to corresponding behavioral visual deficits. While it is acknowledged that early-onset and longstanding blindness leads the occipital cortex to respond to non-visual stimulation, it remains unknown whether a short and transient period of postnatal visual deprivation is sufficient to trigger crossmodal reorganization that persists after years of visual experience. In the present study, we characterized brain responses to auditory stimuli in 11 adults who had been deprived of all patterned vision at birth by congenital cataracts in both eyes until they were treated at 9 to 238 days of age. When compared to controls with typical visual experience, the cataract-reversal group showed enhanced auditory-driven activity in focal visual regions. A combination of dynamic causal modeling with Bayesian model selection indicated that this auditory-driven activity in the occipital cortex was better explained by direct cortico-cortical connections with the primary auditory cortex than by subcortical connections. Thus, a short and transient period of visual deprivation early in life leads to enduring large-scale crossmodal reorganization of the brain circuitry typically dedicated to vision. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Postnatal development of the endbulb of Held in congenitally deaf cats

    Directory of Open Access Journals (Sweden)

    Christa A Baker

    2010-05-01

    Full Text Available The endbulbs of Held are formed by the ascending branches of myelinated auditory nerve fibers and represent one of the largest synaptic endings in the brain. Normally, these endings are highly branched and each can form up to 1000 dome-shaped synapses. The deaf white cat is a model of congenital deafness involving a type of cochleosaccular degeneration that mimics the Scheibe deformity in humans. Mature deaf white cats exhibit reduced endbulb branching, hypertrophy of postsynaptic densities (PSDs, and changes in synaptic vesicle density. Because cats are essentially deaf at birth, we wanted to determine if the progression of brain abnormalities was linked in time to the failure of normal hearing development. The rationale was that the lack of sound-evoked activity would trigger pathologic change in deaf kittens. The cochleae of deaf cats did not exhibit abnormal morphology at birth. After the first postnatal week, however, the presence of a collapsed scala media signaled the difference between deaf and hearing cats. By working backwards in age, endbulbs of deaf cats expressed flattened and elongated PSDs and increased synaptic vesicle density as compared to normal endbulbs. These differences are present at birth in some white kittens, presaging deafness despite their normal cochlear histology. We speculate that hearing pathology is signaled by a perinatal loss of spontaneous bursting activity in auditory nerve fibers or perhaps by some factor released by hair cell synapses before obliteration of the organ of Corti.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Didecanoyl phosphatidylcholine is a superior substrate for assaying mammalian phospholipase D

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Jensen, T.; Morgan, C.P.

    1996-01-01

    Phospholipase D (PLD) activity in crude or solubilized membranes from mammalian tissues is difficult to detect with the current assay techniques, unless a high radioactive concentration of substrate and/or long incubation times are employed. Generally, the enzyme has to be extracted and partially...... purified on one column before easy detection of activity. Furthermore, PLD activity in cultured cells can only be detected by the available assay techniques in the presence of guanosine 5'-[¿-thio]triphosphate (GTP[S]) and a cytosolic factor [usually ADP-ribosylation factor (Arf)]. In this paper we report...... that the use of didecanoyl phosphatidylcholine (C-PC) in mammalian PLD assays considerably increases the detection limit. C-PC was compared with the commonly used dipalmitoyl phosphatidylcholine (C-PC) as a substrate for PLD activity from membranes of human neutrophils, human placenta and pig brain, and from...

  20. 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.

  1. Spatiotemporal expression of chondroitin sulfate sulfotransferases in the postnatal developing mouse cerebellum.

    Science.gov (United States)

    Ishii, Maki; Maeda, Nobuaki

    2008-08-01

    Chondroitin sulfate (CS) proteoglycans are major components of the cell surface and the extracellular matrix in the developing brain and bind to various proteins via CS chains in a CS structure-dependent manner. This study demonstrated the expression pattern of three CS sulfotransferase genes, dermatan 4-O-sulfotransferase (D4ST), uronyl 2-O-sulfotransferase (UST), and N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), in the mouse postnatal cerebellum. These sulfotransferases are responsible for the biosynthesis of oversulfated structures in CS chains such as B, D, and E units, which constitute the binding sites for various heparin-binding proteins. Real-time reverse transcription-polymerase chain reaction analysis indicated that the expression of UST increased remarkably during cerebellar development. The amounts of B and D units, which are generated by UST activity, in the cerebellar CS chains also increased during development. In contrast, the expression of GalNAc4S-6ST and its biosynthetic product, E unit, decreased during postnatal development. In situ hybridization experiments revealed the levels of UST and GalNAc4S-6ST mRNAs to correlate inversely in many cells including Purkinje cells, granule cells in the external granular layer, and inhibitory interneurons. In these neurons, the expression of UST increased and that of GalNAc4S-6ST decreased during development and/or maturation. D4ST was also expressed by many neurons, but its expression was not simply correlated with development, which might contribute to the diversification of CS structures expressed by distinct neurons. These results suggest that the CS structures of various cerebellar neurons change during development and such changes of CS are involved in the regulation of various signaling pathways.

  2. Pyramidal cell development: postnatal spinogenesis, dendritic growth, axon growth, and electrophysiology.

    Directory of Open Access Journals (Sweden)

    Guy eElston

    2014-08-01

    Full Text Available Here we review recent findings related to postnatal spinogenesis, dendritic and axon growth, pruning and electrophysiology of neocortical pyramidal cells in the developing primate brain. Pyramidal cells in sensory, association and executive cortex grow dendrites, spines and axons at different rates, and vary in the degree of pruning. Of particular note is the fact that pyramidal cells in primary visual area (V1 prune more spines than they grow during postnatal development, whereas those in inferotemporal (TEO and TE and granular prefrontal cortex (gPFC; Brodmann’s area 12 grow more than they prune. Moreover, pyramidal cells in TEO, TE and the gPFC continue to grow larger dendritic territories from birth into adulthood, replete with spines, whereas those in V1 become smaller during this time. The developmental profile of intrinsic axons also varies between cortical areas: those in V1, for example, undergo an early proliferation followed by pruning and local consolidation into adulthood, whereas those in area TE tend to establish their territory and consolidate it into adulthood with little pruning. We correlate the anatomical findings with the electrophysiological properties of cells in the different cortical areas, including membrane time constant, depolarizing sag, duration of individual action potentials, and spike-frequency adaptation. All of the electrophysiological variables ramped up before 7 months of age in V1, but continued to ramp up over a protracted period of time in area TE. These data suggest that the anatomical and electrophysiological profiles of pyramidal cells vary among cortical areas at birth, and continue to diverge into adulthood. Moreover, the data reveal that the use it or lose it notion of synaptic reinforcement may speak to only part of the story, use it but you still might lose it may be just as prevalent in the cerebral cortex.

  3. Postnatal reduction of BDNF regulates the developmental remodeling of taste bud innervation.

    Science.gov (United States)

    Huang, Tao; Ma, Liqun; Krimm, Robin F

    2015-09-15

    The refinement of innervation is a common developmental mechanism that serves to increase the specificity of connections following initial innervation. In the peripheral gustatory system, the extent to which innervation is refined and how refinement might be regulated is unclear. The initial innervation of taste buds is controlled by brain-derived neurotrophic factor (BDNF). Following initial innervation, taste receptor cells are added and become newly innervated. The connections between the taste receptor cells and nerve fibers are likely to be specific in order to retain peripheral coding mechanisms. Here, we explored the possibility that the down-regulation of BDNF regulates the refinement of taste bud innervation during postnatal development. An analysis of BDNF expression in Bdnf(lacZ/+) mice and real-time reverse transcription polymerase chain reaction (RT-PCR) revealed that BDNF was down-regulated between postnatal day (P) 5 and P10. This reduction in BDNF expression was due to a loss of precursor/progenitor cells that express BDNF, while the expression of BDNF in the subpopulations of taste receptor cells did not change. Gustatory innervation, which was identified by P2X3 immunohistochemistry, was lost around the perimeter where most progenitor/precursor cells are located. In addition, the density of innervation in the taste bud was reduced between P5 and P10, because taste buds increase in size without increasing innervation. This reduction of innervation density was blocked by the overexpression of BDNF in the precursor/progenitor population of taste bud cells. Together these findings indicate that the process of BDNF restriction to a subpopulation of taste receptor cells between P5 and P10, results in a refinement of gustatory innervation. We speculate that this refinement results in an increased specificity of connections between neurons and taste receptor cells during development. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma.

    Science.gov (United States)

    Bernhard, Wolfgang; Raith, Marco; Kunze, Rebecca; Koch, Vera; Heni, Martin; Maas, Christoph; Abele, Harald; Poets, Christian F; Franz, Axel R

    2015-08-01

    Choline is essential to human development, particularly of the brain in the form of phosphatidylcholine, sphingomyelin and acetylcholine, for bile and lipoprotein formation, and as a methyl group donator. Choline is actively transported into the fetus, and maternal supply correlates with cognitive outcome. Interruption of placental supply may therefore impair choline homeostasis in preterm infants. Determination of postnatal plasma concentrations of choline and its derivatives betaine and dimethylglycine (DMG) in preterm infants compared to cord and maternal blood matched for postmenstrual age (PMA). We collected plasma of very low-birth-weight infants undergoing neonatal intensive care (n = 162), cord plasma of term and preterm infants (n = 176, 24-42-week PMA), serum of parturients (n = 36), and plasma of healthy premenopausal women (n = 40). Target metabolites were analyzed with tandem mass spectrometry and reported as median (25th/75th percentiles). Cord plasma choline concentration was 41.4 (31.8-51.2) µmol/L and inversely correlated with PMA. In term but not in preterm infants, cord plasma choline was lower in girls than in boys. Prenatal glucocorticoid treatment did not affect choline levels in cord plasma, whereas betaine was decreased and DMG increased. In parturients and non-pregnant women, choline concentrations were 14.1 (10.3-16.9) and 8.8 (5.7-11.2) µmol/L, respectively, whereas betaine was lowest in parturients. After delivery, preterm infant plasma choline decreased to 20.8 (16.0-27.6) µmol/L within 48 h. Betaine and DMG correlated with plasma choline in all groups. In preterm infants, plasma choline decreases to 50 % of cord plasma concentrations, reflecting choline undernourishment and postnatal metabolic adaptation, and potentially contributing to impaired outcome.

  5. Postnatal reduction of BDNF regulates the developmental remodeling of taste bud innervation

    Science.gov (United States)

    Huang, Tao; Ma, Liqun; Krimm, Robin F

    2015-01-01

    The refinement of innervation is a common developmental mechanism that serves to increase the specificity of connections following initial innervation. In the peripheral gustatory system, the extent to which innervation is refined and how refinement might be regulated is unclear. The initial innervation of taste buds is controlled by brain-derived neurotrophic factor (BDNF). Following initial innervation, taste receptor cells are added and become newly innervated. The connections between the taste receptor cells and nerve fibers are likely to be specific in order to retain peripheral coding mechanisms. Here, we explored the possibility that the down-regulation of BDNF regulates the refinement of taste bud innervation during postnatal development. An analysis of BDNF expression in BdnflacZ/+ mice and real-time reverse transcription polymerase chain reaction (RT-PCR) revealed that BDNF was down-regulated between postnatal day (P) 5 and P10. This reduction in BDNF expression was due to a loss of precursor/progenitor cells that express BDNF, while the expression of BDNF in the subpopulations of taste receptor cells did not change. Gustatory innervation, which was identified by P2X3 immunohistochemistry, was lost around the perimeter where most progenitor/precursor cells are located. In addition, the density of innervation in the taste bud was reduced between P5 and P10, because taste buds increase in size without increasing innervation. This reduction of innervation density was blocked by the overexpression of BDNF in the precursor/progenitor population of taste bud cells. Together these findings indicate that the process of BDNF restriction to a subpopulation of taste receptor cells between P5 and P10, results in a refinement of gustatory innervation. We speculate that this refinement results in an increased specificity of connections between neurons and taste receptor cells during development. PMID:26164656

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

    Science.gov (United States)

    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.

  7. Molecular phenotyping of transient postnatal tyrosine hydroxylase neurons in the rat bed nucleus of the stria terminalis.

    Science.gov (United States)

    Carter, David A

    2017-07-01

    The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in the forebrain, composed of multiple sub-nuclei, each with discrete populations of neurons. Progress in understanding BNST function, both in the adult and during postnatal maturation, is dependent upon a more complete characterization of neuronal phenotypes in the BNST. The aim of the current study was to define the molecular phenotype of one postnatal BNST neuronal population, in order to identify molecular factors that may underlie both (protein marker-related) immaturity, and secondly, the transience of this phenotype. This BNST population was originally identified by high, but transient expression of the EGR1 transcription factor (TF) in postnatal rat lateral intermediate BNST (BNSTLI). The current results confirm a high level of Egr1 activation in postnatal day 10 (PN10) male BNSTLI that is lost at PN40, and now demonstrate a similar pattern of transient activation in female brains. Apparent cellular immaturity in this population, as indicated by low levels of the adult neuronal marker NeuN/RBFOX3, was found to be uncorrelated with both key neuronal regulator protein expression (SOX2 and REST), and also RBFOX2 protein levels. The BNSTLI neurons have a partial catecholaminergic phenotype (tyrosine hydroxylase-positive/dopa decarboxylase-negative; TH+ve/DDC-ve) that is lost at PN40. In contrast, the co-expressed neuropeptide, somatostatin, is maintained, albeit at lower levels, at PN40. The transcriptional basis of the transient and partial catecholaminergic phenotype was investigated by analysing TFs known to maintain adult dopaminergic (TH+ve/DDC+ve) neuronal phenotypes. The BNSTLI neurons were shown to lack forkhead TFs including FOXA1, FOXA2 and FOXO1. In addition, the BNSTLI neurons had low, primarily cytoplasmic, expression of NR4A2/NURR1, an orphan nuclear receptor that is critical for adult maintenance of midbrain dopamine neurons. These results detail the molecular features

  8. 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.

  9. Postnatal development of the myenteric plexus in cat stomach.

    Science.gov (United States)

    Lolova, I; Itsev, D

    1983-01-01

    The postnatal development of the myenteric plexus in cat stomach has been studied at birth, on the 14th, 30th, 45th and 180th postnatal days, using light- and electronmicroscopic methods. In newborn kittens the main network of the Auerbach plexus is well formed, but the myenteric ganglia are composed of nerve cells with different maturity and a scarce neuropile. During the first two postnatal weeks the dimensions of the ganglia increase owing to the increase of the nerve bodies and the rising number of glials cells and intercellular fibres. This is accompanied by a potentiation of the AChE-activity, mainly in the nerve cell bodies and to a lesser extent in the neuropile. Impregnation reveals different in calibre and form nerve fibres and terminals. Different ultrastructural types of neurones are identified on the 14th day. Later development is expressed in the formation of large compact ganglia and thick connecting strands. The number of AChE-positive fibres in the neuropile increases. Owing to the increase in the cell organelles and their more advanced maturity, it is possible to define the ultrastructural type of an ever increasing number of neurones.

  10. Neuronal Subtype Generation During Postnatal Olfactory Bulb Neurogenesis.

    Science.gov (United States)

    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.

  11. Neuronal Subtype Generation During Postnatal Olfactory Bulb Neurogenesis

    Directory of Open Access Journals (Sweden)

    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.

  12. Brain tumors in children and adolescents and exposure to animals and farm life

    DEFF Research Database (Denmark)

    Christensen, Jeppe Schultz; Mortensen, Laust Hvas; Röösli, Martin

    2012-01-01

    The etiology of brain tumors in children and adolescents is largely unknown, and very few environmental risk factors have been identified. The aim of this study was to examine the relationship between pre- or postnatal animal contacts or farm exposures and the risk of childhood brain tumors (CBTs...

  13. Coupling of organotypic brain slice cultures to silicon-based arrays of electrodes

    DEFF Research Database (Denmark)

    Jahnsen, Henrik; Kristensen, Bjarne Winther; Thiébaud, P

    1999-01-01

    Fetal or early postnatal brain tissue can be cultured in viable and healthy condition for several weeks with development and preservation of the basic cellular and connective organization as so-called organotypic brain slice cultures. Here we demonstrate and describe how it is possible to establish...

  14. Effect of cadmium on lipid metabolism of brain. In vivo incorporation of labelled acetate into lipids

    Energy Technology Data Exchange (ETDEWEB)

    Gulati, S; Gill, K D; Nath, R

    1987-01-01

    The effect of early postnatal cadmium exposure on the in vivo incorporation of (1-/sup 14/C) sodium acetate into various lipid classes of the weanling rat brain was studied. A stimulated incorporation of the label was observed in total lipids, phospholipids, cholesterol, cerebrosides and sulphatides of the brain of Cd-exposed animals compared to controls.

  15. Postnatal changes in local cerebral blood flow measured by the quantitative autoradiographic [14C]iodoantipyrine technique in freely moving rats

    International Nuclear Information System (INIS)

    Nehlig, A.; Pereira de Vasconcelos, A.; Boyet, S.

    1989-01-01

    The postnatal changes in local cerebral blood flow in freely moving rats were measured by means of the quantitative autoradiographic [ 14 C]iodoantipyrine method. The animals were studied at 10, 14, 17, 21 and 35 days and at the adult stage. At 10 days after birth, rates of blood flow were very low and quite homogeneous in most cerebral structures except in a few posterior areas. From these relatively uniform levels, values of local cerebral blood flow rose notably to reach a peak at 17 days in all brain regions studied. Rates of blood flow decreased between 17 and 21 days after birth and then increased from weaning time to reach the known characteristic distribution of the adult rat. The postnatal evolution of local cerebral blood in the rat is in good agreement with previous studies in other species such as dog and humans that also show higher rates of cerebral blood flow and glucose utilization at immature stages. However, in the rat, local cerebral blood flow and local cerebral glucose utilization are not coupled over the whole postnatal period studied, since blood flow rates reach peak values at 17 days whereas glucose utilization remains still quite low at that stage. The high rate of cerebral blood flow in the 17-day-old rat may reflect the energetic and biosynthetic needs of the actively developing brain that are completed by the summation of glucose and ketone body utilization

  16. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  17. Developmental changes of l-arginine transport at the blood-brain barrier in rats.

    Science.gov (United States)

    Tachikawa, Masanori; Hirose, Shirou; Akanuma, Shin-Ichi; Matsuyama, Ryo; Hosoya, Ken-Ichi

    2018-05-01

    l-Arginine is required for regulating synapse formation/patterning and angiogenesis in the developing brain. We hypothesized that this requirement would be met by increased transporter-mediated supply across the blood-brain barrier (BBB). Thus, the purpose of this work was to test the idea that elevation of blood-to-brain l-arginine transport across the BBB in the postnatal period coincides with up-regulation of cationic acid transporter 1 (CAT1) expression in developing brain capillaries. We found that the apparent brain-to-plasma concentration ratio (Kp, app) of l-arginine after intravenous administration during the first and second postnatal weeks was 2-fold greater than that at the adult stage. Kp, app of l-serine was also increased at the first postnatal week. In contrast, Kp, app of d-mannitol, a passively BBB-permeable molecule, did not change, indicating that increased transport of l-arginine and l-serine is not due to BBB immaturity. Double immunohistochemical staining of CAT1 and a marker protein, glucose transporter 1, revealed that CAT1 was localized on both luminal and abluminal membranes of brain capillary endothelial cells during the developmental and adult stages. A dramatic increase in CAT1 expression in the brain was seen at postnatal day 7 (P7) and day 14 (P14) and the expression subsequently decreased as the brain matured. In accordance with this, intense immunostaining of CAT1 was observed in brain capillaries at P7 and P14. These findings strongly support our hypothesis and suggest that the supply of blood-born l-arginine to the brain via CAT1 at the BBB plays a key role in meeting the elevated demand for l-arginine in postnatal brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. 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

  19. Quality and uptake of antenatal and postnatal care in Haiti.

    Science.gov (United States)

    Mirkovic, Kelsey R; Lathrop, Eva; Hulland, Erin N; Jean-Louis, Reginald; Lauture, Daniel; D'Alexis, Ghislaine Desinor; Handzel, Endang; Grand-Pierre, Reynold

    2017-02-02

    Despite improvement, maternal mortality in Haiti remains high at 359/100,000 live births. Improving access to high quality antenatal and postnatal care has been shown to reduce maternal mortality and improve newborn outcomes. Little is known regarding the quality and uptake of antenatal and postnatal care among Haitian women. Exit interviews were conducted with all pregnant and postpartum women seeking care from large health facilities (n = 10) in the Nord and Nord-Est department and communes of St. Marc, Verrettes, and Petite Rivière in Haiti over the study period (March-April 2015; 3-4 days/facility). Standard questions related to demographics, previous pregnancies, current pregnancy, and services/satisfaction during the visit were asked. Total number of antenatal visits were abstracted from charts of recently delivered women (n = 1141). Provider knowledge assessments were completed by antenatal and postnatal care providers (n = 39). Frequencies were calculated for descriptive variables and multivariable logistic regression was used to explore predictors of receiving 5 out of 10 counseling messages among pregnant women. Among 894 pregnant women seeking antenatal care, most reported receiving standard clinical service components during their visit (97% were weighed, 80% had fetal heart tones checked), however fewer reported receiving recommended counseling messages (44% counselled on danger signs, 33% on postpartum family planning). Far fewer women were seeking postnatal care (n = 63) and similar service patterns were reported. Forty-three percent of pregnant women report receiving at least 5 out of 10 counseling messages. Pregnant women on a repeat visit and women with greater educational attainment had greater odds of reporting having received 5 out of 10 counseling messages (2 nd visit: adjusted odds ratio [aOR] =1.70, 95% confidence interval [CI]: 1.09-2.66; 5+ visit: aOR = 5.44, 95% CI: 2.91-10.16; elementary school certificate: a

  20. Barriers to utilization of postnatal care at village level in Klaten district, central Java Province, Indonesia.

    Science.gov (United States)

    Probandari, Ari; Arcita, Akhda; Kothijah, Kothijah; Pamungkasari, Eti Poncorini

    2017-08-07

    Maternal health remains a persisting public health challenge in Indonesia. Postnatal complications, in particular, are considered as maternal health problems priority that should be addressed. Conducting adequate care for postnatal complications will improve the quality of life of mothers and babies. With the universal health coverage implementation, the Indonesian government provides free maternal and child health services close to clients at the village level, which include postnatal care. Our study aimed to explore barriers to utilization of postnatal care at the village level in Klaten district, Central Java Province, Indonesia. A qualitative study was conducted in March 2015 - June 2016 in Klaten district, Central Java, Indonesia. We selected a total of 19 study participants, including eight mothers with postnatal complications, six family members, and five village midwives for in-depth interviews. We conducted a content analysis technique on verbatim transcripts of the interviews using open code software. This study found three categories of barriers to postnatal care utilization in villages: mother and family members' health literacy on postnatal care, sociocultural beliefs and practices, and health service responses. Most mothers did not have adequate knowledge and skills regarding postnatal care that reflected how they lacked awareness and practice of postnatal care. Inter-generational norms and myths hindered mothers from utilizing postnatal care and from having adequate nutritional intake during the postnatal period. Mothers and family members conducted unsafe self-treatment to address perceived minor postnatal complication. Furthermore, social power from extended family influenced the postnatal care health literacy for mother and family members. Postnatal care in the village lacked patient-centered care practices. Additionally, midwives' workloads and capacities to conduct postnatal information, education and counseling were also issues. Despite the

  1. Neuroprotective effects of Ellagic acid on Neonatal Hypoxic Brain ...

    African Journals Online (AJOL)

    Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses. Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post- natal day 10 ...

  2. 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

  3. Mammalian Synthetic Biology: Time for Big MACs.

    Science.gov (United States)

    Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

    2016-10-21

    The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-potentially up to chromosome scale-and the effective delivery of these large DNA payloads to the host cell. Random integration of large transgenes, encoding therapeutic proteins or genetic circuits into host chromosomes, has several drawbacks such as risks of insertional mutagenesis, lack of control over transgene copy-number and position-specific effects; these can compromise the intended functioning of genetic circuits. The development of a system orthogonal to the endogenous genome is therefore beneficial. Mammalian artificial chromosomes (MACs) are functional, add-on chromosomal elements, which behave as normal chromosomes-being replicating and portioned to daughter cells at each cell division. They are deployed as useful gene expression vectors as they remain independent from the host genome. MACs are maintained as a single-copy and can accommodate multiple gene expression cassettes of, in theory, unlimited DNA size (MACs up to 10 megabases have been constructed). MACs therefore enabled control over ectopic gene expression and represent an excellent platform to rapidly prototype and characterize novel synthetic gene circuits without recourse to engineering the host genome. This review describes the obstacles synthetic biologists face when working with mammalian systems and how the development of improved MACs can overcome these-particularly given the spectacular advances in DNA synthesis and assembly that are fuelling this research area.

  4. Mammalian niche conservation through deep time.

    Directory of Open Access Journals (Sweden)

    Larisa R G DeSantis

    Full Text Available Climate change alters species distributions, causing plants and animals to move north or to higher elevations with current warming. Bioclimatic models predict species distributions based on extant realized niches and assume niche conservation. Here, we evaluate if proxies for niches (i.e., range areas are conserved at the family level through deep time, from the Eocene to the Pleistocene. We analyze the occurrence of all mammalian families in the continental USA, calculating range area, percent range area occupied, range area rank, and range polygon centroids during each epoch. Percent range area occupied significantly increases from the Oligocene to the Miocene and again from the Pliocene to the Pleistocene; however, mammalian families maintain statistical concordance between rank orders across time. Families with greater taxonomic diversity occupy a greater percent of available range area during each epoch and net changes in taxonomic diversity are significantly positively related to changes in percent range area occupied from the Eocene to the Pleistocene. Furthermore, gains and losses in generic and species diversity are remarkably consistent with ~2.3 species gained per generic increase. Centroids demonstrate southeastern shifts from the Eocene through the Pleistocene that may correspond to major environmental events and/or climate changes during the Cenozoic. These results demonstrate range conservation at the family level and support the idea that niche conservation at higher taxonomic levels operates over deep time and may be controlled by life history traits. Furthermore, families containing megafauna and/or terminal Pleistocene extinction victims do not incur significantly greater declines in range area rank than families containing only smaller taxa and/or only survivors, from the Pliocene to Pleistocene. Collectively, these data evince the resilience of families to climate and/or environmental change in deep time, the absence of

  5. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    International Nuclear Information System (INIS)

    Zhang, Pengpeng; Shan, Tizhong; Liang, Xinrong; Deng, Changyan; Kuang, Shihuan

    2014-01-01

    Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor flox/flox mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor flox/flox mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function

  6. Mammalian developmental genetics in the twentieth century.

    Science.gov (United States)

    Artzt, Karen

    2012-12-01

    This Perspectives is a review of the breathtaking history of mammalian genetics in the past century and, in particular, of the ways in which genetic thinking has illuminated aspects of mouse development. To illustrate the power of that thinking, selected hypothesis-driven experiments and technical advances are discussed. Also included in this account are the beginnings of mouse genetics at the Bussey Institute, Columbia University, and The Jackson Laboratory and a retrospective discussion of one of the classic problems in developmental genetics, the T/t complex and its genetic enigmas.

  7. Nutrient acquisition strategies of mammalian cells.

    Science.gov (United States)

    Palm, Wilhelm; Thompson, Craig B

    2017-06-07

    Mammalian cells are surrounded by diverse nutrients, such as glucose, amino acids, various macromolecules and micronutrients, which they can import through transmembrane transporters and endolysosomal pathways. By using different nutrient sources, cells gain metabolic flexibility to survive periods of starvation. Quiescent cells take up sufficient nutrients to sustain homeostasis. However, proliferating cells depend on growth-factor-induced increases in nutrient uptake to support biomass formation. Here, we review cellular nutrient acquisition strategies and their regulation by growth factors and cell-intrinsic nutrient sensors. We also discuss how oncogenes and tumour suppressors promote nutrient uptake and thereby support the survival and growth of cancer cells.

  8. Preservation of mammalian germ plasm by freezing

    Energy Technology Data Exchange (ETDEWEB)

    Mazur, P.

    1978-01-01

    Embryos of several mammalian species can be frozen to -196/sup 0/C (or below) by procedures that result in the thawed embryos being indistinguishable from their unfrozen counterparts. The survival often exceeds 90%, and in liquid nitrogen it should remain at that high level for centuries. Sublethal biochemical changes are also precluded at -196/sup 0/C. No developmental abnormalities have been detected in mouse offspring derived from frozen-thawed embryos, and, since all the manipulations are carried out on the preimplantation stages, none would be expected.

  9. Mammalian cell culture capacity for biopharmaceutical manufacturing.

    Science.gov (United States)

    Ecker, Dawn M; Ransohoff, Thomas C

    2014-01-01

    : With worldwide sales of biopharmaceuticals increasing each year and continuing growth on the horizon, the manufacture of mammalian biopharmaceuticals has become a major global enterprise. We describe the current and future industry wide supply of manufacturing capacity with regard to capacity type, distribution, and geographic location. Bioreactor capacity and the use of single-use products for biomanufacturing are also profiled. An analysis of the use of this capacity is performed, including a discussion of current trends that will influence capacity growth, availability, and utilization in the coming years.

  10. Mammalian Gravity Receptors: Structure and Metabolism

    Science.gov (United States)

    Ross, M. D.

    1985-01-01

    Calcium metabolism in mammalian gravity receptors is examined. To accomplish this objective it is necessary to study both the mineral deposits of the receptors, the otoconia, and the sensory areas themselves, the saccular and utricular maculas. The main focus was to elucidate the natures of the organic and inorganic phases of the crystalline masses, first in rat otoconia but more recently in otoliths and otoconia of a comparative series of vertebrates. Some of the ultrastructural findings in rat maculas, however, have prompted a more thorough study of the organization of the hair cells and innervation patterns in graviceptors.

  11. Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic-Ischemic Fetal Lambs during Postnatal Life.

    Science.gov (United States)

    Rey-Santano, Carmen; Mielgo, Victoria E; Gastiasoro, Elena; Murgia, Xabier; Lafuente, Hector; Ruiz-Del-Yerro, Estibaliz; Valls-I-Soler, Adolf; Hilario, Enrique; Alvarez, Francisco J

    2011-01-01

    The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic-ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3 h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury.

  12. Brain-Gut-Microbe Communication in Health and Disease

    OpenAIRE

    Sue eGrenham; Gerard eClarke; Gerard eClarke; John F Cryan; John F Cryan; Timothy G Dinan; Timothy G Dinan

    2011-01-01

    Bidirectional signalling between the gastrointestinal tract and the brain is regulated at neural, hormonal and immunological levels. This construct is known as the brain-gut axis and is vital for maintaining homeostasis. Bacterial colonisation of the intestine plays a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signalling. Recent research advances have seen a tremendous i...

  13. Current insights in brain protection for the sick newborn infant

    OpenAIRE

    KOOI E.M.W.

    2015-01-01

    This paper presents an overview of the modern antenatal and postnatal strategies in brain protection for both preterm and term born infants. It is known, that the two most common causes of neonatal brain injury are prematurity and hypoxic-ischemic encephalopathy (HIE) in the term born infant. Approximately one in nine babies is born before term. Nowadays these preterm born infants more often survive the neonatal period due to developments in treatment options in the last decades. They are how...

  14. Development and Tissue Origins of the Mammalian Cranial Base

    Science.gov (United States)

    Iseki, S.; Bamforth, S. D.; Olsen, B. R.; Morriss-Kay, G. M.

    2008-01-01

    The vertebrate cranial base is a complex structure composed of bone, cartilage and other connective tissues underlying the brain; it is intimately connected with development of the face and cranial vault. Despite its central importance in craniofacial development, morphogenesis and tissue origins of the cranial base have not been studied in detail in the mouse, an important model organism. We describe here the location and time of appearance of the cartilages of the chondrocranium. We also examine the tissue origins of the mouse cranial base using a neural crest cell lineage cell marker, Wnt1-Cre/R26R, and a mesoderm lineage cell marker, Mesp1-Cre/R26R. The chondrocranium develops between E11 and E16 in the mouse, beginning with development of the caudal (occipital) chondrocranium, followed by chondrogenesis rostrally to form the nasal capsule, and finally fusion of these two parts via the midline central stem and the lateral struts of the vault cartilages. X-Gal staining of transgenic mice from E8.0 to 10 days post-natal showed that neural crest cells contribute to all of the cartilages that form the ethmoid, presphenoid, and basisphenoid bones with the exception of the hypochiasmatic cartilages. The basioccipital bone and non-squamous parts of the temporal bones are mesoderm derived. Therefore the prechordal head is mostly composed of neural crest-derived tissues, as predicted by the New Head Hypothesis. However, the anterior location of the mesoderm-derived hypochiasmatic cartilages, which are closely linked with the extra-ocular muscles, suggests that some tissues associated with the visual apparatus may have evolved independently of the rest of the “New Head”. PMID:18680740

  15. Mesozoic mammals from Arizona: new evidence on Mammalian evolution.

    Science.gov (United States)

    Jenkins, F A; Crompton, A W; Downs, W R

    1983-12-16

    Knowledge of early mammalian evolution has been based on Old World Late Triassic-Early Jurassic faunas. The discovery of mammalian fossils of approximately equivalent age in the Kayenta Formation of northeastern Arizona gives evidence of greater diversity than known previously. A new taxon documents the development of an angular region of the jaw as a neomorphic process, and represents an intermediate stage in the origin of mammalian jaw musculature.

  16. Synthetic RNA Controllers for Programming Mammalian Cell Fate and Function

    Science.gov (United States)

    2015-11-04

    Final report for “Synthetic RNA controllers for programming mammalian cell fate and function” Principal Investigator: Christina D. Smolke...SUBTITLE Synthetic RNA controllers for programming mammalian cell fate and function 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18   2 Synthetic RNA controllers for programming mammalian cell fate and function Task 1

  17. Post natal use of analgesics: comparisons between conventional postnatal wards and a maternity hotel.

    Science.gov (United States)

    Nordeng, Hedvig; Eskild, Anne; Nesheim, Britt-Ingjerd

    2010-04-01

    To investigate factors related to analgesic use after delivery, and especially whether rates of analgesic use were different in a midwife-managed maternity hotel as compared to conventional postnatal wards. One maternity hotel and two conventional postnatal wards at Ullevål University Hospital in Oslo, Norway. Data were obtained from hospital records for 804 women with vaginal deliveries. Postnatal analgesic use. Overall, approximately half the women used analgesics after vaginal delivery in both conventional postnatal wards and maternity hotel. The factors that were significantly associated with use of analgesics postnatally in multivariate analysis were multiparity, having a non-Western ethnicity, smoking in pregnancy, younger age, instrumental delivery, analgesic use during labour, maternal complications post partum, and duration of postnatal stay 4 days or more. The use of analgesics is determined by socio-demographic and obstetric factors rather than the organisation of the ward.

  18. Ecology and evolution of mammalian biodiversity.

    Science.gov (United States)

    Jones, Kate E; Safi, Kamran

    2011-09-12

    Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future.

  19. The mammalian ovary from genesis to revelation.

    Science.gov (United States)

    Edson, Mark A; Nagaraja, Ankur K; Matzuk, Martin M

    2009-10-01

    Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago.

  20. Ecology and evolution of mammalian biodiversity

    Science.gov (United States)

    Jones, Kate E.; Safi, Kamran

    2011-01-01

    Mammals have incredible biological diversity, showing extreme flexibility in eco-morphology, physiology, life history and behaviour across their evolutionary history. Undoubtedly, mammals play an important role in ecosystems by providing essential services such as regulating insect populations, seed dispersal and pollination and act as indicators of general ecosystem health. However, the macroecological and macroevolutionary processes underpinning past and present biodiversity patterns are only beginning to be explored on a global scale. It is also particularly important, in the face of the global extinction crisis, to understand these processes in order to be able to use this knowledge to prevent future biodiversity loss and loss of ecosystem services. Unfortunately, efforts to understand mammalian biodiversity have been hampered by a lack of data. New data compilations on current species' distributions, ecologies and evolutionary histories now allow an integrated approach to understand this biodiversity. We review and synthesize these new studies, exploring the past and present ecology and evolution of mammalian biodiversity, and use these findings to speculate about the mammals of our future. PMID:21807728

  1. Focusing on RISC assembly in mammalian cells.

    Science.gov (United States)

    Hong, Junmei; Wei, Na; Chalk, Alistair; Wang, Jue; Song, Yutong; Yi, Fan; Qiao, Ren-Ping; Sonnhammer, Erik L L; Wahlestedt, Claes; Liang, Zicai; Du, Quan

    2008-04-11

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi.

  2. Focusing on RISC assembly in mammalian cells

    International Nuclear Information System (INIS)

    Hong Junmei; Wei Na; Chalk, Alistair; Wang Jue; Song, Yutong; Yi Fan; Qiao Renping; Sonnhammer, Erik L.L.; Wahlestedt, Claes; Liang Zicai; Du, Quan

    2008-01-01

    RISC (RNA-induced silencing complex) is a central protein complex in RNAi, into which a siRNA strand is assembled to become effective in gene silencing. By using an in vitro RNAi reaction based on Drosophila embryo extract, an asymmetric model was recently proposed for RISC assembly of siRNA strands, suggesting that the strand that is more loosely paired at its 5' end is selectively assembled into RISC and results in target gene silencing. However, in the present study, we were unable to establish such a correlation in cell-based RNAi assays, as well as in large-scale RNAi data analyses. This suggests that the thermodynamic stability of siRNA is not a major determinant of gene silencing in mammalian cells. Further studies on fork siRNAs showed that mismatch at the 5' end of the siRNA sense strand decreased RISC assembly of the antisense strand, but surprisingly did not increase RISC assembly of the sense strand. More interestingly, measurements of melting temperature showed that the terminal stability of fork siRNAs correlated with the positions of the mismatches, but not gene silencing efficacy. In summary, our data demonstrate that there is no definite correlation between siRNA stability and gene silencing in mammalian cells, which suggests that instead of thermodynamic stability, other features of the siRNA duplex contribute to RISC assembly in RNAi

  3. 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.

  4. 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.

  5. Women's experiences of postnatal distress: a qualitative study.

    Science.gov (United States)

    Coates, Rose; Ayers, Susan; de Visser, Richard

    2014-10-14

    Women can experience a range of psychological problems after birth, including anxiety, depression and adjustment disorders. However, research has predominantly focused on depression. Qualitative work on women's experiences of postnatal mental health problems has sampled women within particular diagnostic categories so not looked at the range of potential psychological problems. The aims of this study were to explore how women experienced and made sense of the range of emotional distress states in the first postnatal year. A qualitative study of 17 women who experienced psychological problems in the first year after having a baby. Semi-structured interviews took place in person (n =15) or on the telephone (n =2). Topics included women's experiences of becoming distressed and their recovery. Data were analysed using Interpretative Phenomenological Analysis (IPA). Themes were developed within each interview before identifying similar themes for multiple participants across interviews, in order to retain an idiographic approach. Psychological processes such as guilt, avoidance and adjustment difficulties were experienced across different types of distress. Women placed these in the context of defining moments of becoming a mother; giving birth and breastfeeding. Four superordinate themes were identified. Two concerned women's unwanted negative emotions and difficulties adjusting to their new role. "Living with an unwelcome beginning" describes the way mothers' new lives with their babies started out with unwelcome emotions, often in the context of birth and breastfeeding difficulties. All women spoke about the importance of their postnatal healthcare experiences in "Relationships in the healthcare system". "The shock of the new" describes women's difficulties adjusting to the demands of motherhood and women emphasised the importance of social support in "Meeting new support needs". These findings emphasise the need for exploration of psychological processes such as

  6. Postnatal medical complications and behavioral inhibition in the offspring

    Directory of Open Access Journals (Sweden)

    Eva Moehler

    2007-01-01

    Full Text Available Se ha sugerido que la inhibición conductual representa un indicador temperamental importante en la predicción del desarrollo emocional del niño, del adolescente e incluso del adulto. En consonancia, el objetivo de este estudio experimental fue investigar el impacto de las complicaciones pre-, peri-, y postnatales sobre la inhibición conductual. Se midió la inhibición conductual de niños que empiezan a andar mediante un procedimiento estandarizado de laboratorio en 101 niños con 14 meses de edad postnatal. Las complicaciones médicas fueron evaluadas a través de las Rutter Scales, tomadas por el examinador de registros médicos de las pacientes internadas, y de documentaciones sobre el embarazo en el caso de las no hospitalizadas. Los criterios de inclusión fueron un peso al nacer por encima de 2500g, 37 semanas o más de gestación y puntuaciones APGAR por encima de 7. Las complicaciones postnatales evaluadas abarcaron ictericia fisiológica, trastornos de adaptación, enfermedades contagiosas, entre otras. Las complicaciones médicas en el periodo postnatal pero no en el pre- o perinatal resultaron aumentar significativamente la inhibición conductual a los 14 meses de edad postnatal. Los esfuerzos preventivos orientados al preescolar y al desarrollo emocional del niño deberían tomar en consideración que los niños con complicaciones neonatal parecen tener un mayor riesgo de presentar trastornos de internalización en su vida posteriormente.

  7. Specificity of chicken and mammalian transferrins in myogenesis

    International Nuclear Information System (INIS)

    Beach, R.L.; Popiela, Heinz; Festoff, B.W.

    1985-01-01

    Chicken transferrins isolated from eggs, embryo extract, serum or ischiatic-peroneal nerves are able to stimulate incorporation of ( 3 H)thymidine, and promote myogenesis by primary chicken muscles cells in vitro. Mammalian transferrins (bovine, rat, mouse, horse, rabbit, and human) do not promote ( 3 H)thymidine incorporation or myotube development. Comparison of the peptide fragments obtained after chemical or limited proteolytic cleavage demonstrates that the four chicken transferrins are all indistinguishable, but they differ considerably from the mammalian transferrins. The structural differences between chicken and mammalian transferrins probably account for the inability of mammalian transferrins to act as mitogens for, and to support myogenesis of, primary chicken muscle cells. (author)

  8. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    International Nuclear Information System (INIS)

    Githu, Tangayi; Merrow, Arnold C.; Lee, Jason K.; Garrison, Aaron P.; Brown, Rebeccah L.

    2014-01-01

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  9. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    Energy Technology Data Exchange (ETDEWEB)

    Githu, Tangayi [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Radiology of Huntsville, P.C., Huntsville, AL (United States); Merrow, Arnold C.; Lee, Jason K. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Garrison, Aaron P. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States); Akron Children' s Hospital, Pediatric Surgery, Akron, OH (United States); Brown, Rebeccah L. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States)

    2014-03-15

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  10. Prenatal and Postnatal Exposure to Persistent Organic Pollutants and Infant Growth

    DEFF Research Database (Denmark)

    Iszatt, N.; Stigum, H.; Verner, M. A.

    2015-01-01

    prenatal and postnatal effects. OBJECTIVES: We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). METHODS: We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p...... growth, and it contains state-of-the-art exposure modeling. Prenatal p,p'-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels....

  11. 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

  12. 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.

  13. Cytokine mRNA profiles in pigs exposed prenatally and postnatally to Schistosoma japonicum

    DEFF Research Database (Denmark)

    Techau, Michala E.; Johansen, Maria V.; Aasted, Bent

    2007-01-01

    of septal fibrosis were significantly higher in the postnatal group compared to the prenatal group (P prenatally infected animals compared to the control...... group (P prenatal group showed higher levels of TGF-beta 1 in the liver compared with the postnatally infected group (P control group (P prenatally exposed pigs.......The pig is a natural host for Schistosoma japonicum and a useful animal model of human infection. The aim of the present study was to assess the differences between the cytokine profiles in prenatally or postnatally S. japonicum exposed pigs. Seven prenatally exposed pigs, 7 postnatally exposed...

  14. Evolution of mammalian endothermic metabolism: leaky membranes as a source of heat

    International Nuclear Information System (INIS)

    Else, P.L.; Hulbert, A.J.

    1987-01-01

    O 2 consumption was measured at 37/degrees/C in tissue slices of liver, kidney, and brain from Amphilbolurus vitticeps and Rattus norvegicus (a reptile and mammal with same weight and body temperature) both in the presence and absence of ouabain. O 2 consumption of the mammalian tissues was two to four times that of the reptilian tissues and the mammalian tissues used three to six times the energy for Na + -K + transport than the reptilian tissues. Passive permeability to 42 K + was measured at 37/degrees/C in liver and kidney slices, and passive permeability to 22 Na + was measured at 37/degrees/C in isolated and cultured liver cells from each species. The mammalian cell membrane was severalfold leakier to both these ions than was the reptilian cell membrane, and thus the membrane pumps must use more energy to maintain the transmembrane ion gradients. It is postulated that this is a general difference between the cells of ectotherms and endotherms and thus partly explains the much higher levels of metabolism found in endothermic mammals

  15. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development

    Directory of Open Access Journals (Sweden)

    Kyle J. Beauchemin

    2016-08-01

    Full Text Available To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ. Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns were used to define a murine Developing Lung Characteristic Subtranscriptome (mDLCS. Regression modeling of the Principal Components supported the four canonical stages of mammalian embryonic lung development (embryonic, pseudoglandular, canalicular, saccular defined previously by morphology and histology. For postnatal alveolar development, the regression model was consistent with four stages of alveolarization characterized by episodic transcriptional activity of genes related to pulmonary vascularization. Genes expressed in a strain-dependent manner were enriched for annotations related to neurogenesis, extracellular matrix organization, and Wnt signaling. Finally, a comparison of mouse and human transcriptomics from pre-natal stages of lung development revealed conservation of pathways associated with cell cycle, axon guidance, immune function, and metabolism as well as organism-specific expression of genes associated with extracellular matrix organization and protein modification. The mouse lung development transcriptome data generated for this study serves as a unique reference set to identify genes and pathways essential for normal mammalian lung development and for investigations into the developmental origins of respiratory disease and cancer. The gene expression data are available from the Gene Expression Omnibus (GEO archive (GSE74243. Temporal expression patterns of mouse genes can be investigated using a study specific web resource (http://lungdevelopment.jax.org.

  16. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development.

    Science.gov (United States)

    Beauchemin, Kyle J; Wells, Julie M; Kho, Alvin T; Philip, Vivek M; Kamir, Daniela; Kohane, Isaac S; Graber, Joel H; Bult, Carol J

    2016-01-01

    To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ). Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns were used to define a murine Developing Lung Characteristic Subtranscriptome (mDLCS). Regression modeling of the Principal Components supported the four canonical stages of mammalian embryonic lung development (embryonic, pseudoglandular, canalicular, saccular) defined previously by morphology and histology. For postnatal alveolar development, the regression model was consistent with four stages of alveolarization characterized by episodic transcriptional activity of genes related to pulmonary vascularization. Genes expressed in a strain-dependent manner were enriched for annotations related to neurogenesis, extracellular matrix organization, and Wnt signaling. Finally, a comparison of mouse and human transcriptomics from pre-natal stages of lung development revealed conservation of pathways associated with cell cycle, axon guidance, immune function, and metabolism as well as organism-specific expression of genes associated with extracellular matrix organization and protein modification. The mouse lung development transcriptome data generated for this study serves as a unique reference set to identify genes and pathways essential for normal mammalian lung development and for investigations into the developmental origins of respiratory disease and cancer. The gene expression data are available from the Gene Expression Omnibus (GEO) archive (GSE74243). Temporal expression patterns of mouse genes can be investigated using a study specific web resource (http://lungdevelopment.jax.org).

  17. Insights into Brain Glycogen Metabolism

    Science.gov (United States)

    Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-01-01

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

  18. Behavioral effects in mice of postnatal exposure to low-doses of 137-cesium and bisphenol A.

    Science.gov (United States)

    Heredia, Luis; Bellés, Montserrat; LLovet, Maria Isabel; Domingo, Jose L; Linares, Victoria

    2016-01-18

    Bisphenol A (BPA) is the most important plasticizer used in many household products such as polycarbonate plastics or epoxy resins. Public and scientific concerns exist regarding the possibility that the neonatal exposure to BPA may contribute to neurobehavioral disorders. On the other hand, there is little information on the effects of low doses of ionizing radiation during critical phases of postnatal brain development, as well as the combination of radiation and environmental chemicals. In this study, C57BL/6J mice were exposed to low doses of internal radiation ((137)Cs), and/or BPA on postnatal day 10 (PND10). At the age of two months, animals were submitted to several tests to assess anxiety, activity, learning, and memory. Results showed that exposure to (137)Cs, alone or in combination with BPA, increased the anxiety-like of the animals without changing the activity levels. Animals exposed to (137)Cs showed impaired learning, and spatial memory, an impairment that was not observed in the groups co-exposed to BPA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. Effects of prenatal 60Co irradiation on postnatal neural, learning, and hormonal development of the squirrel monkey

    International Nuclear Information System (INIS)

    Ordy, J.M.; Brizzee, K.R.; Dunlap, W.P.; Knight, C.

    1982-01-01

    The goals of this study were to examine the effects of 0, 50, and 100 rad of 60 Co administered prenatally on postnatal development of neuromuscular coordination, visual discrimination learning, spontaneous light-dark stabilimeter activity, plasma cortisol, and somatometric growth rates of diurnal squirrel monkeys from birth to 90 days. In terms of accuracy, completeness, and time required for performance of reflexes and neuromuscular coordination, the performance of 50- and 100-rad offspring was less accurate and poorly coordinated and required more time for completion to that of controls. In visual orientation, discrimination, and reversal learning, the percentage correct responses of the 50- and 100-rad offspring were significantly lower than those of controls. Spontaneous light-dark stabilimeter activity of 50- and 100-rad offspring was significantly higher in the dark session than that of controls. Plasma cortisol was significantly higher in 100-rad infants than in controls. Comparisons of somatometric growth rates indicated that postnatal head circumference, crown-rump length, and to a lesser extent body weight increased at significantly slower rates in 50- and 100-rad offspring. These findings should provide essential information for formulating and carrying out multivariate behavioral, biochemical, and morphometric assessments of low-dose effects on the brain of primate offspring within demonstrable dose-response curves

  2. Behavioral effects in mice of postnatal exposure to low-doses of 137-cesium and bisphenol A

    International Nuclear Information System (INIS)

    Heredia, Luis; Bellés, Montserrat; LLovet, Maria Isabel; Domingo, Jose L.; Linares, Victoria

    2016-01-01

    Bisphenol A (BPA) is the most important plasticizer used in many household products such as polycarbonate plastics or epoxy resins. Public and scientific concerns exist regarding the possibility that the neonatal exposure to BPA may contribute to neurobehavioral disorders. On the other hand, there is little information on the effects of low doses of ionizing radiation during critical phases of postnatal brain development, as well as the combination of radiation and environmental chemicals. In this study, C57BL/6J mice were exposed to low doses of internal radiation ( 137 Cs), and/or BPA on postnatal day 10 (PND10). At the age of two months, animals were submitted to several tests to assess anxiety, activity, learning, and memory. Results showed that exposure to 137 Cs, alone or in combination with BPA, increased the anxiety-like of the animals without changing the activity levels. Animals exposed to 137 Cs showed impaired learning, and spatial memory, an impairment that was not observed in the groups co-exposed to BPA.

  3. The perception of pre- and post-natal marijuana exposure on health outcomes: A content analysis of twitter messages.

    Science.gov (United States)

    Dakkak, H; Brown, R; Twynstra, J; Charbonneau, K; Seabrook, J A

    2018-05-23

    The prevalence of marijuana use during pregnancy ranges from 3- 30% , and most of this is for recreational purposes. Marijuana exposure during pregnancy has been linked with low birth weight babies and other adverse child health outcomes. Twitter is a popular news and social networking outlet, and is frequently used to access information about population health and behavior. The primary objective of this study was to investigate the types of messages disseminated on Twitter about marijuana use and infant and maternal health. The secondary objective was to describe the reported health outcomes associated with prenatal and postnatal marijuana use. Tweets were collected from the inception of Twitter (2006) until April 2017. If tweets included links, these links were examined to investigate the source of the message and to clarify the user's intent. In total, 550 tweets were captured, with most tweets (77.6%) having a neutral tweet tone, suggesting uncertainty about the health effects associated with pre- and post-natal marijuana exposure. The sources attached to the original tweets, however, were more likely to report on negative health outcomes. The most common health outcomes associated with prenatal marijuana exposure were: poor brain development (27.3%), inadequate development of the nervous system (23.6%), low birth weight (23.3%), poor behavioral outcomes (21.0%), and infant memory issues (19.3%). The inverse association between marijuana use and the quality and quantity of milk produced by the mother was the most commonly reported tweet for the lactation period.

  4. Effects of postnatal malnutrition and senescence on learning, long-term memory, and extinction in the rat.

    Science.gov (United States)

    Martínez, Yvonne; Díaz-Cintra, Sofía; León-Jacinto, Uriel; Aguilar-Vázquez, Azucena; Medina, Andrea C; Quirarte, Gina L; Prado-Alcalá, Roberto A

    2009-10-12

    There is a wealth of information indicating that the hippocampal formation is important for learning and memory consolidation. The hippocampus is very sensitive to ageing and developmentally stressful factors such as prenatal malnutrition, which produces anatomical alterations of hippocampal pyramidal cells as well as impaired spatial learning. On the other hand, there are no reports about differential effects of postnatal malnutrition, installed at birth and maintained all through life in young and aged rats, on learning and memory of active avoidance, a task with an important procedural component. We now report that learning and long-term retention of this task were impaired in young malnourished animals, but not in young control, senile control, and senile malnourished Sprague-Dawley rats; young and senile rats were 90 and 660 days of age, respectively. Extinction tests showed, however, that long-term memory of the malnourished groups and senile control animals is impaired as compared with the young control animals. These data strongly suggest that the learning and long-term retention impairments seen in the young animals were due to postnatal malnutrition; in the senile groups, this cognitive alteration did not occur, probably because ageing itself is an important factor that enables the brain to engage in compensatory mechanisms that reduce the effects of malnutrition. Nonetheless, ageing and malnutrition, conditions known to produce anatomic and functional hippocampal alterations, impede the maintenance of long-term memory, as seen during the extinction test.

  5. Prenatal complex rhythmic music sound stimulation facilitates postnatal spatial learning but transiently impairs memory in the domestic chick.

    Science.gov (United States)

    Kauser, H; Roy, S; Pal, A; Sreenivas, V; Mathur, R; Wadhwa, S; Jain, S

    2011-01-01

    Early experience has a profound influence on brain development, and the modulation of prenatal perceptual learning by external environmental stimuli has been shown in birds, rodents and mammals. In the present study, the effect of prenatal complex rhythmic music sound stimulation on postnatal spatial learning, memory and isolation stress was observed. Auditory stimulation with either music or species-specific sounds or no stimulation (control) was provided to separate sets of fertilized eggs from day 10 of incubation. Following hatching, the chicks at age 24, 72 and 120 h were tested on a T-maze for spatial learning and the memory of the learnt task was assessed 24 h after training. In the posthatch chicks at all ages, the plasma corticosterone levels were estimated following 10 min of isolation. The chicks of all ages in the three groups took less (p memory after 24 h of training, only the music-stimulated chicks at posthatch age 24 h took a significantly longer (p music sounds facilitates spatial learning, though the music stimulation transiently impairs postnatal memory. 2011 S. Karger AG, Basel.

  6. Antenatal and postnatal depression: A public health perspective

    Directory of Open Access Journals (Sweden)

    Saurabh R Shrivastava

    2015-01-01

    Full Text Available Depression is widely prevalent among women in the child-bearing age, especially during the antenatal and postnatal period. Globally, post-partum depression has been reported in almost 10% to 20% of mothers, and it can start from the moment of birth, or may result from depression evolving continuously since pregnancy. The presence of depression among women has gained a lot of attention not only because of the rising incidence or worldwide distribution, but also because of the serious negative impact on personal, family and child developmental outcomes. Realizing the importance of maternal depression on different aspects-personal, child, and familial life, there is a crucial need to design a comprehensive public health policy (including a mental health strategy, to ensure that universal psychosocial assessment in perinatal women is undertaken within the primary health care system. To conclude, depression during pregnancy and in the postnatal period is a serious public health issue, which essentially requires continuous health sector support to eventually benefit not only the woman, but also the family, the community, and health care professionals.

  7. Postnatal outcomes of prenatally diagnosed 45,X/46,XX.

    Science.gov (United States)

    Tokita, Mari J; Sybert, Virginia P

    2016-05-01

    High quality information is critical for informed decision-making in pregnancy following a prenatal diagnosis of sex chromosome aneuploidy. The goal of this study was to define the spectrum of outcomes in patients with prenatally diagnosed 45,X/46,XX mosaic Turner syndrome in order to provide a better basis for genetic counseling at the time of intrauterine diagnosis. Phenotype data for twenty-five patients with prenatally diagnosed 45,X/46,XX mosaicism were collected by retrospective chart review and, when possible, semi-structured telephone interview. Existing data from a cohort of 58 patients with postnatally diagnosed 45,X/46,XX mosaicism were used for comparison. Relative to those diagnosed postnatally, prenatal patients were more likely to have normal growth and normal secondary sexual development, less likely to manifest distinctive Turner syndrome features such as nuchal webbing and edema, and had significantly fewer renal defects. These differences underscore the need for a nuanced approach to prenatal counseling in cases of 45,X/46,XX mosaicism. © 2016 Wiley Periodicals, Inc.

  8. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Katsuda

    2014-01-01

    Full Text Available We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam. The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta.

  9. Prenatal and postnatal cocaine exposure predict teen cocaine use

    Science.gov (United States)

    Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

    2015-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

  10. Postnational or National Europe? European Asylum Policies and Immigration Controls

    Directory of Open Access Journals (Sweden)

    Vedrana Baričević

    2011-01-01

    Full Text Available The paper deals with the theories of the transformation of the modern functions of the nation state and the immigrant membership associated with the (legally defined status of community members exemplified by asylum policies. In the process, two fundamental approaches to the issue are distinguished: the first one emphasizing changes in the institution of the traditional national citizenship and competences of the nation state, while stressing a predominantly national character of the institution of citizenship, and the second one, which emphasizes the transformation of traditional citizenships, stressing the weakening of the role of the nation state. Therefore, in the latter case, there is increasingly more talk about postnationalism, which is a term denoting the transformation of the substantive aspects of citizenship in the EU countries. The mentioned theoretical approaches are applied to three groups of issues. First, the impact of the EU on the processes of the globalisation of the rights of asylum migrants are examined. Second, the paper works out the details of the way of formulating the policy of asylum membership in the EU member states. Third, the question of whether universal postnational inclusion of asylum migrants is at work in the EU member states, or whether the status of this group of immigrants should be found within the limits of the traditional theory of state membership and national sovereignty is addressed

  11. Prenatal and postnatal cocaine exposure predict teen cocaine use.

    Science.gov (United States)

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Mouse models for the study of postnatal cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    A. Del Olmo-Turrubiarte

    2015-06-01

    Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

  13. Developmental synchrony of thalamocortical circuits in the neonatal brain.

    Science.gov (United States)

    Poh, Joann S; Li, Yue; Ratnarajah, Nagulan; Fortier, Marielle V; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D; Meaney, Michael J; Qiu, Anqi

    2015-08-01

    The thalamus is a deep gray matter structure and consists of axonal fibers projecting to the entire cortex, which provide the anatomical support for its sensorimotor and higher-level cognitive functions. There is limited in vivo evidence on the normal thalamocortical development, especially in early life. In this study, we aimed to investigate the developmental patterns of the cerebral cortex, the thalamic substructures, and their connectivity with the cortex in the first few weeks of the postnatal brain. We hypothesized that there is developmental synchrony of the thalamus, its cortical projections, and corresponding target cortical structures. We employed diffusion tensor imaging (DTI) and divided the thalamus into five substructures respectively connecting to the frontal, precentral, postcentral, temporal, and parietal and occipital cortex. T2-weighted magnetic resonance imaging (MRI) was used to measure cortical thickness. We found age-related increases in cortical thickness of bilateral frontal cortex and left temporal cortex in the early postnatal brain. We also found that the development of the thalamic substructures was synchronized with that of their respective thalamocortical connectivity in the first few weeks of the postnatal life. In particular, the right thalamo-frontal substructure had the fastest growth in the early postnatal brain. Our study suggests that the distinct growth patterns of the thalamic substructures are in synchrony with those of the cortex in early life, which may be critical for the development of the cortical and subcortical functional specialization. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. A universal mammalian vaccine cell line substrate.

    Directory of Open Access Journals (Sweden)

    Jackelyn Murray

    Full Text Available Using genome-wide small interfering RNA (siRNA screens for poliovirus, influenza A virus and rotavirus, we validated the top 6 gene hits PV, RV or IAV to search for host genes that when knocked-down (KD enhanced virus permissiveness and replication over wild type Vero cells or HEp-2 cells. The enhanced virus replication was tested for 12 viruses and ranged from 2-fold to >1000-fold. There were variations in virus-specific replication (strain differences across the cell lines examined. Some host genes (CNTD2, COQ9, GCGR, NDUFA9, NEU2, PYCR1, SEC16G, SVOPL, ZFYVE9, and ZNF205 showed that KD resulted in enhanced virus replication. These findings advance platform-enabling vaccine technology, the creation of diagnostic cells substrates, and are informative about the host mechanisms that affect virus replication in mammalian cells.

  15. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

    Mathur, Melina; Xiang, Joy S; Smolke, Christina D

    2017-01-02

    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

  16. Modeling Exposure of Mammalian Predatorsto Anticoagulant Rodenticides

    DEFF Research Database (Denmark)

    Topping, Christopher John; Elmeros, Morten

    2016-01-01

    as vectors of AR, and was used to evaluate likely impacts of restrictions imposed on AR use in Denmark banning the use of rodenticides for plant protection in woodlands and tree-crops. The model uses input based on frequencies and timings of baiting for rodent control for urban, rural and woodland locations......Anticoagulant rodenticides (AR) are a widespread and effective method of rodent control but there is concern about the impact these may have on non-target organisms, in particular secondary poisoning of rodent predators. Incidence and concentration of AR in free-living predators in Denmark is very...... high. We postulate that this is caused by widespread exposure due to widespread use of AR in Denmark in and around buildings. To investigate this theory a spatio-temporal model of AR use and mammalian predator distribution was created. This model was supported by data from an experimental study of mice...

  17. Physiological significance of polyploidization in mammalian cells.

    Science.gov (United States)

    Pandit, Shusil K; Westendorp, Bart; de Bruin, Alain

    2013-11-01

    Programmed polyploidization occurs in all mammalian species during development and aging in selected tissues, but the biological properties of polyploid cells remain obscure. Spontaneous polyploidization arises during stress and has been observed in a variety of pathological conditions, such as cancer and degenerative diseases. A major challenge in the field is to test the predicted functions of polyploidization in vivo. However, recent genetic mouse models with diminished polyploidization phenotypes represent novel, powerful tools to unravel the biological function of polyploidization. Contrary to a longstanding hypothesis, polyploidization appears to not be required for differentiation and has no obvious impact on proliferation. Instead, polyploidization leads to increased cell size and genetic diversity, which could promote better adaptation to chronic injury or stress. We discuss here the consequences of reducing polyploidization in mice and review which stress responses and molecular signals trigger polyploidization during development and disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. X-rays sensitive mammalian cell mutant

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi

    1982-01-01

    A phenomenon that in x-ray-sensitive mammalian-cell mutants, cellular death due to x-ray radiation was not increased by caffeine, but on the contrary, the dead cells were resuscitated by it was discussed. The survival rate of mutant cells increased by caffein in a low concentration. This suggested that caffeine may have induced some mechanism to produce x-ray resistant mutant cells. Postirradiation treatment with caffeine increased considerably the survival rate of the mutant cells, and this suggested the existence of latent caffeine-sensitive potentially lethal damage repair system. This system, after a few hours, is thought to be substituted by caffeine-resistant repair system which is induced by caffeine, and this may be further substituted by x-ray-resistant repair system. The repair system was also induced by adenine. (Ueda, J.)

  19. Redox signaling during hypoxia in mammalian cells

    Directory of Open Access Journals (Sweden)

    Kimberly A. Smith

    2017-10-01

    Full Text Available Hypoxia triggers a wide range of protective responses in mammalian cells, which are mediated through transcriptional and post-translational mechanisms. Redox signaling in cells by reactive oxygen species (ROS such as hydrogen peroxide (H2O2 occurs through the reversible oxidation of cysteine thiol groups, resulting in structural modifications that can change protein function profoundly. Mitochondria are an important source of ROS generation, and studies reveal that superoxide generation by the electron transport chain increases during hypoxia. Other sources of ROS, such as the NAD(PH oxidases, may also generate oxidant signals in hypoxia. This review considers the growing body of work indicating that increased ROS signals during hypoxia are responsible for regulating the activation of protective mechanisms in diverse cell types.

  20. Peromyscus as a Mammalian Epigenetic Model

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    Kimberly R. Shorter

    2012-01-01

    Full Text Available Deer mice (Peromyscus offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied. Peromyscus resources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involving Peromyscus models. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using a Peromyscus model of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects, Peromyscus models have a great potential.

  1. Mechanosensor Channels in Mammalian Somatosensory Neurons

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    Patrick Delmas

    2007-09-01

    Full Text Available Mechanoreceptive sensory neurons innervating the skin, skeletal muscles andviscera signal both innocuous and noxious information necessary for proprioception, touchand pain. These neurons are responsible for the transduction of mechanical stimuli intoaction potentials that propagate to the central nervous system. The ability of these cells todetect mechanical stimuli impinging on them relies on the presence of mechanosensitivechannels that transduce the external mechanical forces into electrical and chemical signals.Although a great deal of information regarding the molecular and biophysical properties ofmechanosensitive channels in prokaryotes has been accumulated over the past two decades,less is known about the mechanosensitive channels necessary for proprioception and thesenses of touch and pain. This review summarizes the most pertinent data onmechanosensitive channels of mammalian somatosensory neurons, focusing on theirproperties, pharmacology and putative identity.

  2. Magnetism in plant and mammalian ferritin

    International Nuclear Information System (INIS)

    Bauminger, E.R.; Nowik, I.

    1989-01-01

    A rich variety of magnetic phenomena is observed in Moessbauer studies of ferritin. Depending on the amount of iron in the horse spleen ferritin core, a paramagnetic relaxation spectrum, or quadrupole split doublet or a magnetically split sextet showing superparamagnetism, are obtained at 4.1 K. Moessbauer studies of the recently prepared iron loaded concanavalin A yield hyperfine parameters identical to those found previously in mammalian ferritin, yet show the existence of larger iron aggregates. Due to the larger particle size it is possible to follow the magnetic hyperfine field and to obtain the magnetic ordering temperature as 240 K. This is exactly the Neel temperature of ferrihydrite, thus establishing that this is indeed the iron compound in the ferritin core. (orig.)

  3. Engineered Trehalose Permeable to Mammalian Cells.

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    Alireza Abazari

    Full Text Available Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra- and extracellular trehalose has been shown to confer improved tolerance against freezing and desiccation. Since mammalian cells do not synthesize nor import trehalose, the development of novel methods for efficient intracellular delivery of trehalose has been an ongoing investigation. Herein, we studied the membrane permeability of engineered lipophilic derivatives of trehalose. Trehalose conjugated with 6 acetyl groups (trehalose hexaacetate or 6-O-Ac-Tre demonstrated superior permeability in rat hepatocytes compared with regular trehalose, trehalose diacetate (2-O-Ac-Tre and trehalose tetraacetate (4-O-Ac-Tre. Once in the cell, intracellular esterases hydrolyzed the 6-O-Ac-Tre molecules, releasing free trehalose into the cytoplasm. The total concentration of intracellular trehalose (plus acetylated variants reached as high as 10 fold the extracellular concentration of 6-O-Ac-Tre, attaining concentrations suitable for applications in biopreservation. To describe this accumulation phenomenon, a diffusion-reaction model was proposed and the permeability and reaction kinetics of 6-O-Ac-Tre were determined by fitting to experimental data. Further studies suggested that the impact of the loading and the presence of intracellular trehalose on cellular viability and function were negligible. Engineering of trehalose chemical structure rather than manipulating the cell, is an innocuous, cell-friendly method for trehalose delivery, with demonstrated potential for trehalose loading in different types of cells and cell lines, and can facilitate the wide-spread application of trehalose as an intracellular protective agent in biopreservation studies.

  4. The DNA damage response in mammalian oocytes

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    John eCarroll

    2013-06-01

    Full Text Available DNA damage is one of the most common insults that challenge all cells. To cope, an elaborate molecular and cellular response has evolved to sense, respond to and correct the damage. This allows the maintenance of DNA fidelity essential for normal cell viability and the prevention of genomic instability that can lead to tumour formation. In the context of oocytes, the impact of DNA damage is not one of tumour formation but of the maintenance of fertility. Mammalian oocytes are particularly vulnerable to DNA damage because physiologically they may lie dormant in the ovary for many years (>40 in humans until they receive the stimulus to grow and acquire the competence to become fertilized. The implication of this is that in some organisms, such as humans, oocytes face the danger of cumulative genetic damage for decades. Thus, the ability to detect and repair DNA damage is essential to maintain the supply of oocytes necessary for reproduction. Therefore, failure to confront DNA damage in oocytes could cause serious anomalies in the embryo that may be propagated in the form of mutations to the next generation allowing the appearance of hereditary disease. Despite the potential impact of DNA damage on reproductive capacity and genetic fidelity of embryos, the mechanisms available to the oocyte for monitoring and repairing such insults have remained largely unexplored until recently. Here, we review the different aspects of the response to DNA damage in mammalian oocytes. Specifically, we address the oocyte DNA damage response from embryonic life to adulthood and throughout oocyte development.

  5. The architecture of mammalian ribosomal protein promoters

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    Perry Robert P

    2005-02-01

    Full Text Available Abstract Background Mammalian ribosomes contain 79 different proteins encoded by widely scattered single copy genes. Coordinate expression of these genes at transcriptional and post-transcriptional levels is required to ensure a roughly equimolar accumulation of ribosomal proteins. To date, detailed studies of only a very few ribosomal protein (rp promoters have been made. To elucidate the general features of rp promoter architecture, I made a detailed sequence comparison of the promoter regions of the entire set of orthologous human and mouse rp genes. Results A striking evolutionarily conserved feature of most rp genes is the separation by an intron of the sequences involved in transcriptional and translational regulation from the sequences with protein encoding function. Another conserved feature is the polypyrimidine initiator, which conforms to the consensus (Y2C+1TY(T2(Y3. At least 60 % of the rp promoters contain a largely conserved TATA box or A/T-rich motif, which should theoretically have TBP-binding capability. A remarkably high proportion of the promoters contain conserved binding sites for transcription factors that were previously implicated in rp gene expression, namely upstream GABP and Sp1 sites and downstream YY1 sites. Over 80 % of human and mouse rp genes contain a transposable element residue within 900 bp of 5' flanking sequence; very little sequence identity between human and mouse orthologues was evident more than 200 bp upstream of the transcriptional start point. Conclusions This analysis has provided some valuable insights into the general architecture of mammalian rp promoters and has identified parameters that might coordinately regulate the transcriptional activity of certain subsets of rp genes.

  6. PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation.

    Science.gov (United States)

    Zhu, Guo; Rankin, Sherri L; Larson, Jon D; Zhu, Xiaoyan; Chow, Lionel M L; Qu, Chunxu; Zhang, Jinghui; Ellison, David W; Baker, Suzanne J

    2017-01-01

    Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into the effect of its loss on outcomes in the brain, we conditionally inactivated the murine Pten gene in neonatal neural stem/progenitor cells. Pten inactivation created an abnormal perivascular proliferative niche in the cerebellum that persisted in adult animals but did not progress to malignancy. Proliferating cells showed undifferentiated morphology and expressed the progenitor marker Nestin but not Math1, a marker of committed granule neuron progenitors. Codeletion of Pten and Trp53 resulted in fully penetrant medulloblastoma originating from the perivascular niche, which exhibited abnormal blood vessel networks and advanced neuronal differentiation of tumor cells. EdU pulse-chase experiments demonstrated a perivascular cancer stem cell population in Pten/Trp53 double mutant medulloblastomas. Genetic analyses revealed recurrent somatic inactivations of the tumor suppressor gene Ptch1 and a recapitulation of the sonic hedgehog subgroup of human medulloblastomas. Overall, our results showed that PTEN acts to prevent the proliferation of a progenitor niche in postnatal cerebellum predisposed to oncogenic induction of medulloblastoma. Cancer Res; 77(1); 123-33. ©2016 AACR. ©2016 American Association for Cancer Research.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Comparison between indigenous and Western postnatal care practices in Mopani District, Limpopo Province, South Africa

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    Roinah N. Ngunyulu

    2015-05-01

    Full Text Available Background: Postnatal care begins immediately after the expulsion of the placenta and continues for six to eight weeks post-delivery. High standard of care is required during the postnatal period because mothers and babies are at risk and vulnerable to complications related to postpartum haemorrhage and infections. Midwives and traditional birth attendants are responsible for the provision of postnatal care in different settings, such as clinics and hospitals, and homes. Methods: A qualitative, exploratory, descriptive and contextual research approach was followed in this study. Unstructured interviews were conducted with the traditional birth attendants. An integrated literature review was conducted to identify the Western postnatalcare practices. Tesch’s process was followed during data analysis. Findings: The following main categories were identified: similarities between indigenous and Western postnatal care practices, and differences between indigenous and Western postnatal care practices. Based on these findings, training of midwives and traditional birth attendants was recommended in order to empower them with knowledge and skills regarding the indigenous and Western postnatal care practices. Conclusions: It is evident that some indigenous postnatal care practices have adverse effects on the health of postnatal women and their newborn infants, but these are unknown to the traditional birth attendants. The employment of indigenous postnatal care practices by the traditional birth attendants is also influenced by their cultural beliefs, norms, values and attitudes. Therefore, there is an urgent need to train midwives and traditional birth attendants regarding the indigenous and Western postnatal care to improve the health of postnatal women and their babies.

  9. Plasma treatment of mammalian vascular cells : A quantitative description

    NARCIS (Netherlands)

    Kieft, IE; Darios, D; Roks, AJM; Stoffels, E

    For the first time, quantitative data was obtained on plasma treatment of living mammalian cells. The nonthermal atmospheric discharge produced by the plasma needle was used for treatment of mammalian endothelial and smooth muscle cells. The influence of several experimental parameters on cell

  10. Plasma treatment of mammalian vascular cells: a quantitative description

    NARCIS (Netherlands)

    Kieft, I.E.; Darios, D.; Roks, A.J.M.; Stoffels - Adamowicz, E.

    2005-01-01

    For the first time, quantitative data was obtained on plasma treatment of living mammalian cells. The nonthermal atmospheric discharge produced by the plasma needle was used for treatment of mammalian endothelial and smooth muscle cells. The influence of several experimental parameters on cell

  11. Adaptive plasticity in mammalian masticatory joints

    Science.gov (United States)

    Ravosa, Matthew J.; Kunwar, Ravinder; Nicholson, Elisabeth K.; Klopp, Emily B.; Pinchoff, Jessie; Stock, Stuart R.; Stack, M. Sharon; Hamrick, Mark W.

    2006-08-01

    Genetically similar white rabbits raised on diets of different mechanical properties, as well as wild-type and myostatin-deficient mice raised on similar diets, were compared to assess the postweaning effects of elevated masticatory loads due to increased jaw-adductor muscle and bite forces on the proportions and properties of the mandibular symphysis and temporomandibular joint (TMJ). Microcomputed tomography (microCT) was used to quantify bone structure at a series of equidistant external and internal sites in coronal sections for a series of joint locations. Discriminant function analyses and non-parametric ANOVAs were used to characterize variation in biomineralization within and between loading cohorts. In both species, long-term excessive loading results in larger joint proportions, thicker articular and cortical bone, and increased biomineralization of hard tissues. Such adaptive plasticity appears designed to maintain the postnatal integrity of masticatory joint systems for a primary loading environment(s). This behavioral signal may be increasingly mitigated in older organisms by the interplay between adaptive and degradative joint tissue responses.

  12. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  13. Dynamic changes in water ADC, energy metabolism, extracellular space volume and tortuosity in neonatal rat brain during irreversible ischemia

    NARCIS (Netherlands)

    Toorn, van der A.; Syková, E.; Dijkhuizen, R.M.; Voríšek, I.; Vargová, L.; Skobisová, E.; Lookeren Campagne, van M.; Reese, T.; Nicolaij, K.

    1996-01-01

    To obtain a better understanding of the mechanisms underlying early changes in the brain water apparent diffusion coefficient (ADC) observed in cerebral ischemia, dynamic changes in the ADC of water and in the energy status were measured at postnatal day 8 or 9 in neonatal rat brains after cardiac

  14. Sex-based differences in gene expression in hippocampus following postnatal lead exposure

    International Nuclear Information System (INIS)

    Schneider, J.S.; Anderson, D.W.; Sonnenahalli, H.; Vadigepalli, R.

    2011-01-01

    The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning.Blood lead levels were 26.7 ± 2.1 μg/dl and 27.1 ± 1.7 μg/dl for females and males, respectively. The expression of 175 unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression of a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex. - Highlights: → Postnatal lead exposure has a significant effect on hippocampal gene expression patterns. → At least one set of genes was affected in opposite directions in males and females. → Differentially expressed genes were associated with diverse biological pathways.

  15. Fenestrations and Various Duplications of the Posterior Communicating Artery in the Prenatal and Postnatal Periods.

    Science.gov (United States)

    Trandafilović, Milena; Vasović, Ljiljana; Vlajković, Slobodan; Đorđević, Gordana; Stojanović, Borisav; Mladenović, Marija

    2016-07-01

    The 2 paired arteries-the posterior communicating arteries (PCoAs) and the precommunicating parts of the posterior cerebral arteries-form the so-called posterior segment of the cerebral arterial circle on the base of the brain. A number of (ab)normal morphologic features were described in the literature (e.g., unusual kinking, or extreme elongations, hypoplasia, duplications, fenestrations, the infundibular widening, or aplasia of the PCoA in the prenatal and/or postnatal periods). The aim of this study was to analyze an incidence of various fenestrations and duplications of the PCoA, and describe their general features and their association with other vascular abnormalities. The research was performed on the brains of 200 human fetuses and 377 adult cadavers of both genders and different ages using microdissection and macrodissection methods. There were 0.34% cases with PCoA fenestrations and 3.12% cases with various PCoA duplications. Their morphologic features were described and compared with the similar PCoA abnormalities recorded in the scientific literature. There was no association between the PCoA and either duplication or aneurysm in adult cases. After thorough examination, the fenestrations and duplications of the PCoA are distinguished as 2 special forms of vascular abnormalities, and the PCoA duplications are characterized as partial and total. Furthermore, whereas the low incidence of a fenestration of the PCoA suggests it to be a sufficiently rare phenomenon, the duplications of the PCoA trunk are fairly frequent, especially concerning its terminal segment. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.

    Science.gov (United States)

    Partearroyo, Teresa; Pérez-Miguelsanz, Juliana; Peña-Melián, Ángel; Maestro-de-Las-Casas, Carmen; Úbeda, Natalia; Varela-Moreiras, Gregorio

    2016-06-01

    The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet.

  17. Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

    Science.gov (United States)

    Chachlaki, Konstantina; Malone, Samuel A; Qualls-Creekmore, Emily; Hrabovszky, Erik; Münzberg, Heike; Giacobini, Paolo; Ango, Fabrice; Prevot, Vincent

    2017-10-15

    Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFP Vglut2 , EYFP Vgat , and GFP Gad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes. © 2017 Wiley Periodicals, Inc.

  18. Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and early postnatal lethality.

    Directory of Open Access Journals (Sweden)

    Jacobus J Dudok

    Full Text Available The serotonin (5-HT system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival.

  19. Staffing in postnatal units: is it adequate for the provision of quality care? Staff perspectives from a state-wide review of postnatal care in Victoria, Australia

    Directory of Open Access Journals (Sweden)

    Lumley Judith

    2006-07-01

    Full Text Available Abstract Background State-wide surveys of recent mothers conducted over the past decade in Victoria, one state of Australia, have identified that women are consistently less satisfied with the care they received in hospital following birth compared with other aspects of maternity care. Little is known of caregivers' perspectives on the provision ofhospital postnatal care: how care is organised and provided in different hospitals; what constrains the provision of postnatal care (apart from funding and what initiatives are being undertaken to improve service delivery. A state-widereview of organisational structures and processes in relation to the provision of hospital postnatal care in Victoria was undertaken. This paper focuses on the impact of staffing issues on the provision of quality postnatal care from the perspective of care providers. Methods A study of care providers from Victorian public hospitals that provide maternity services was undertaken. Datawere collected in two stages. Stage one: a structured questionnaire was sent to all public hospitals in Victoria that provided postnatal care (n = 73, exploring the structure and organisation of care (e.g. staffing, routine observations, policy framework and discharge planning. Stage two: 14 maternity units were selected and invited to participate in a more in-depth exploration of postnatal care. Thirty-eight key informant interviews were undertaken with midwives (including unit managers, associate unit managers and clinical midwives and a medical practitioner from eachselected hospital. Results Staffing was highlighted as a major factor impacting on the provision of quality postnatal care. There were significant issues associated with inadequate staff/patient ratios; staffing mix; patient mix; prioritisation of birth suites over postnatal units; and the use of non-permanent staff. Forty-three percent of hospitals reported having only midwives (i.e. no non-midwives providing postnatal care

  20. Androgen imprinting of the brain in animal models and humans with intersex disorders: review and recommendations.

    Science.gov (United States)

    Hrabovszky, Zoltan; Hutson, John M

    2002-11-01

    Psychosexual development, gender assignment and surgical treatment in patients with intersex are controversial issues in the medical literature. Some groups are of the opinion that gender identity and sexual orientation are determined prenatally secondary to the fetal hormonal environment causing irreversible development of the nervous system. We reviewed the evidence in animal and human studies to determine the possible role of early postnatal androgen production in gender development. An extensive literature review was performed of data from animal experiments and human studies. RESULTS Many animal studies show that adding or removing hormonal stimulus in early postnatal life can profoundly alter gender behavior of the adult animal. Human case studies show that late intervention is unable to reverse gender orientation from male to female. Most studies have not permitted testing of whether early gender assignment and treatment as female with suppression/ablation of postnatal androgen production leads to improved concordance of the gender identity and sex of rearing. Animal studies support a role for postnatal androgens in brain/behavior development with human studies neither completely supportive nor antagonistic. Therefore, gender assignment in infants with intersex should be made with the possibility in mind that postnatal testicular hormones at ages 1 to 6 months may affect gender identity. A case-control study is required to test the hypothesis that postnatal androgen exposure may convert ambisexual brain functions to committed male behavior patterns.

  1. Fetal adrenal gland enlargement - prenatal and postnatal management.

    Science.gov (United States)

    Lackova, Eliska; Cunderlik, Anton; Ticha, Lubica; Gabor, Maria

    2017-11-01

    The enlargement of suprarenal gland is related to preterm birth and the birth weight. The ultrasound measurement of fetal adrenal gland volume may identify women at risk for impending preterm birth. The aim of our study was to investigate the newborns in the region of western Slovakia followed up due to suprarenal gland enlargement. To set the ratio of prenatally diagnosed suprarenal gland enlargment, postnatal managment and treatment and interventions. The newborns with congenital adrenal hyperplasia were excluded. We have analyzed 6 years of medical records of all cases from the western Slovakia region of suprarenal gland enlargement encountered to 1st Pediatric Department, Children's University Hospital Bratislava Republic in the time period of January 2010 to Janurary 2016. The diagnosis of suprarenal gland enlargement was set by ultrasound examination performed on the 4th postnatal day as an overall screening test. Newborns with positive laboratory screening on congenital adrenal hyperplasia (CAH) were excluded from our study. We analyzed the origin of surarenal gland enlargement, gestation week on the due date, the birth weight and other comorbidities and genetic pathologies in newborns with the enlarged suprarenal glands. There were 6 newborns followed up due to suprarenal gland enlargement. All of the patients had diagnosed the adrenal haemorrhage. Adrenal lesions like adrenal cysts or neuroblastomas were not confirmed. All of the adrenal enlargements were benign with no need of other medical or surgical intervention. None of the newborn patients had other genetic abnormalities, mineral or hormonal imbalances, problems with arterial pressure or haemodynamic instability. All of the patients underwent at least 5 prenatal ultrasound tests and at least 2 postnatal ultrasound measurements. The avarage birth weight was 3030 grams (2700 grams - to 3750 grams). The avarage birth lenght was 50 cm (47 centimeter to 53 cm).The average gestation week (gw) on due date

  2. Maternal low protein diet and postnatal high fat diet increases adipose imprinted gene expression

    Science.gov (United States)

    Maternal and postnatal diet can alter Igf2 gene expression and DNA methylation. To test whether maternal low protein and postnatal high fat (HF) diet result in alteration in Igf2 expression and obesity, we fed obese-prone Sprague-Dawley rats 8% (LP) or 20% (NP) protein for 3 wk prior to breeding and...

  3. 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

  4. Maternal Postnatal Depression and the Development of Depression in Offspring up to 16 Years of Age

    Science.gov (United States)

    Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Goodyer, Ian; Cooper, Peter

    2011-01-01

    Objective: The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. Method: This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702…

  5. Depression in Men in the Postnatal Period and Later Child Psychology: A Population Cohort Study

    Science.gov (United States)

    Ramchandani, Paul G.; Stein, Alan; O'Connor, Thomas G.; Heron, Jon; Murray, Lynne; Evans, Jonathan

    2008-01-01

    The factors responsible for depression in men following childbirth and the association between their depression in the postnatal period and later psychiatric disorders in their children are assessed. Findings show that depression in fathers in their postnatal period is associated with later psychiatric disorders in their children, independent of…

  6. Thyroid function profile in cord blood and postnatal changes at 24 ...

    African Journals Online (AJOL)

    Background: Studying the acute postnatal changes of newborn thyroid function is essential for determining the best timing of screening for congenital hypothyroidism. There is paucity of literature on neonatal thyroid function and particularly the postnatal changes in Nigeria. Objectives: To describe the profile of thyroid ...

  7. Myosin heavy chain expression in rabbit masseter muscle during postnatal development

    NARCIS (Netherlands)

    Bredman, J. J.; Weijs, W. A.; Korfage, H. A.; Brugman, P.; Moorman, A. F.

    1992-01-01

    The expression of isoforms of myosin heavy chain (MHC) during postnatal development was studied in the masseter muscle of the rabbit. Evidence is presented that in addition to adult fast and slow myosin, the rabbit masseter contains neonatal and 'cardiac' alpha-MHC. During postnatal growth myosin

  8. The postnatal progeny development of males whose sexual cells were irradiated during different stages of spermatogenesis

    International Nuclear Information System (INIS)

    Lepekhin, N.P.; Palyga, G.F.

    1995-01-01

    Distinct genetic radiosensitivity if germinal cells of males irradiated during different stages of spermatogenesis with doses of 0.25-5.0 Gy leads to reduction in vital newborn rats number in the first generation progeny and to elevated postnatal mortality rate. These postnatal ontogeny disorders depend on the irradiation dose and spermatogenesis stage for a moment irradiation. 11 refs.; 4 tabs

  9. Pre- and Postnatal Women's Leisure Time Physical Activity Patterns: A Multilevel Longitudinal Analysis

    Science.gov (United States)

    Cramp, Anita G.; Bray, Steven R.

    2009-01-01

    The purpose of this study was to examine women's leisure time physical activity (LTPA) before pregnancy, during pregnancy, and through the first 7 months postnatal. Pre- and postnatal women (n = 309) completed the 12-month Modifiable Activity Questionnaire and demographic information. Multilevel modeling was used to estimate a growth curve…

  10. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  11. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  12. Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK-801 Administration

    Directory of Open Access Journals (Sweden)

    Chunmei Guo

    2010-01-01

    Full Text Available Neonatal blockade of N-methyl-D-aspartic acid (NMDA receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND 5 through 14. Open-field test was performed on PND 42, and PND 77 to examine the validity of the current model. BDNF protein levels in hippocampus and prefrontal cortex (PFC were analyzed on PND 15, PND 42, and PND 77. Results showed that neonatal challenge with MK-801 persistently elevated locomotor activity as well as BDNF expression; the alterations in BDNF expression varied at different developing stages and among brain regions. However, these findings provide neurochemical evidence that the blockade of NMDA receptors during brain development results in long-lasting alterations in BDNF expression and might contribute to neurobehavioral pathology of the present animal model for schizophrenia. Further study in the mechanisms and roles of the BDNF may lead to better understanding of the pathophysiology of schizophrenia.

  13. Postnatal Ablation of Synaptic Retinoic Acid Signaling Impairs Cortical Information Processing and Sensory Discrimination in Mice.

    Science.gov (United States)

    Park, Esther; Tjia, Michelle; Zuo, Yi; Chen, Lu

    2018-06-06

    knock-out mouse, we performed multiple regional/cell-type-specific manipulation of RARα expression in the postnatal brain, and show that RARα signaling contributes to normal whisker-dependent texture discrimination as well as regulating spine dynamics of apical dendrites from layer (L5) pyramidal neurons in S1. Deletion of RARα in excitatory neurons in the forebrain induces elevated spine elimination and impaired sensory discrimination. Our study provides novel insights into the role of RARα signaling in cortical processing and experience-dependent spine maturation. Copyright © 2018 the authors 0270-6474/18/385277-12$15.00/0.

  14. Glutamatergic and GABAergic neurotransmitter cycling and energy metabolism in rat cerebral cortex during postnatal development.

    Science.gov (United States)

    Chowdhury, Golam M I; Patel, Anant B; Mason, Graeme F; Rothman, Douglas L; Behar, Kevin L

    2007-12-01

    The contribution of glutamatergic and gamma-aminobutyric acid (GABA)ergic neurons to oxidative energy metabolism and neurotransmission in the developing brain is not known. Glutamatergic and GABAergic fluxes were assessed in neocortex of postnatal day 10 (P10) and 30 (P30) urethane-anesthetized rats infused intravenously with [1,6-(13)C(2)]glucose for different time intervals (time course) or with [2-(13)C]acetate for 2 to 3 h (steady state). Amino acid levels and (13)C enrichments were determined in tissue extracts ex vivo using (1)H-[(13)C]-NMR spectroscopy. Metabolic fluxes were estimated from the best fits of a three-compartment metabolic model (glutamatergic neurons, GABAergic neurons, and astroglia) to the (13)C-enrichment time courses of amino acids from [1,6-(13)C(2)]glucose, constrained by the ratios of neurotransmitter cycling (V(cyc))-to-tricarboxylic acid (TCA) cycle flux (V(TCAn)) calculated from the steady-state [2-(13)C]acetate enrichment data. From P10 to P30 increases in total neuronal (glutamate plus GABA) TCA cycle flux (3 x ; 0.24+/-0.05 versus 0.71+/-0.07 micromol per g per min, Pcycling flux (3.1 to 5 x ; 0.07 to 0.11 (+/-0.03) versus 0.34+/-0.03 micromol per g per min, Pcycling (DeltaV(cyc(tot))) and neuronal TCA cycle flux (DeltaV(TCAn(tot))) between P10 and P30 were 0.23 to 0.27 and 0.47 micromol per g per min, respectively, similar to the approximately 1:2 relationship previously reported for adult cortex. For the individual neurons, increases in V(TCAn) and V(cyc) were similar in magnitude (glutamatergic neurons, 2.7 x versus 2.8 to 4.6 x ; GABAergic neurons, approximately 5 x versus approximately 7 x), although GABAergic flux changes were larger. The findings show that glutamate and GABA neurons undergo large and approximately proportional increases in neurotransmitter cycling and oxidative energy metabolism during this major postnatal growth spurt.

  15. Hypoxia-induced lipid peroxidation in the brain during postnatal ontogenesis

    Czech Academy of Sciences Publication Activity Database

    Rauchová, Hana; Vokurková, Martina; Koudelová, J.

    2012-01-01

    Roč. 61, Suppl.1 (2012), S89-S101 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GAP304/12/0259 Institutional research plan: CEZ:AV0Z50110509 Keywords : hypobaric hypoxia * reactive oxygen species (ROS) * polyunsaturated fatty acids * Na * K-ATPase * catalase * L-carnitine Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.531, year: 2012

  16. The experience of seeking help for postnatal depression.

    Science.gov (United States)

    Holopainen, Debbi

    2002-01-01

    This qualitative study sought to explore women's experiences of support and treatment for postnatal depression. In-depth interviews from seven women were analysed using the phenomenological method described by Creswell (1998). Findings indicate that partners provided women the most support. The women did not know where to seek professional help, often being identified and helped by the maternal health nurse who monitors and guides the progress of their babies' development. Hospital programs were criticised for not informing and involving family. The women were dissatisfied with hospital doctors and their GPs claiming they had limited time for counselling, preferring to prescribe medication that alleviated symptoms but reinforced feelings of inadequacy. Recommendations are made to involve families and to use the unique position of the maternal health nurse in assessing new mothers.

  17. Roles of MicroRNA across Prenatal and Postnatal Periods

    Directory of Open Access Journals (Sweden)

    Ilaria Floris

    2016-11-01

    Full Text Available Communication between mother and offspring in mammals starts at implantation via the maternal–placental–fetal axis, and continues postpartum via milk targeted to the intestinal mucosa. MicroRNAs (miRNAs, short, noncoding single-stranded RNAs, of about 22 nucleotides in length, are actively involved in many developmental and physiological processes. Here we highlight the role of miRNA in the dynamic signaling that guides infant development, starting from implantation of conceptus and persisting through the prenatal and postnatal periods. miRNAs in body fluids, particularly in amniotic fluid, umbilical cord blood, and breast milk may offer new opportunities to investigate physiological and/or pathological molecular mechanisms that portend to open novel research avenues for the identification of noninvasive biomarkers.

  18. Postnatal development of plasma amino acids in hyperphagic rats.

    Science.gov (United States)

    Salvadó, M J; Segués, T; Arola, L

    1991-01-01

    The effect of feeding a highly palatable high-energy cafeteria diet on individual amino acid levels in plasma during postnatal development of the rat has been evaluated and compared to chow-fed controls. The cafeteria diet selected by the rats was hypercaloric and hyperlipidic, with practically the same amount of carbohydrate as the control diet, and slightly hyperproteic. In response to cafeteria feeding, significant decreases were observed in plasma serine and cysteine along the period studied. Significant changes with age during the growth period were shown by cafeteria-fed animals, which were not observed in control rats. Citrulline levels were lower on days 10 and 14 in cafeteria pups than in chow pups. Methionine was highest on day 30. Threonine was also higher at days 20 and 30, as was valine but with a nadir at day 10. Lysine showed maximal values on days 14 and 30.

  19. Developing electrical properties of postnatal mouse lumbar motoneurons

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    Jacques eDurand

    2015-09-01

    Full Text Available We studied the rapid changes in electrical properties of lumbar motoneurons between postnatal days 3 and 9 just before mice weight-bear and walk. The input conductance and rheobase significantly increased up to P8. A negative correlation exists between the input resistance and rheobase. Both parameters are significantly correlated with the total dendritic surface area of motoneurons, the largest motoneurons having the lowest input resistance and the highest rheobase. We classified the motoneurons into three groups according to their discharge firing patterns during current pulse injection (transient, delayed onset, sustained. The delayed onset firing type has the highest rheobase and the fastest action potential whereas the transient firing group has the lowest rheobase and the less mature action potential. We found 32% and 10 % of motoneurons with a transient firing at P3-P5 and P8, respectively. About 20% of motoneurons with delayed onset firing were detected at P8. At P9, all motoneurons exhibit a sustained firing. We defined five groups of motoneurons according to their discharge firing patterns in response to ascending and descending current ramps. In addition to the four classical types, we defined a fifth type called transient for the quasi-absence of discharge during the descending phase of the ramp. This transient type represents about 40% between P3-P5 and tends to disappear with age. Types 1 and 2 (linear and clockwise hysteresis are the most preponderant at P6-P7. Types 3 and 4 (prolonged sustained and counter clockwise hysteresis emerge at P8-P9. The emergence of type 3 and 4 probably depends on the maturation of L type calcium channels in the dendrites of motoneurons. No correlation was found between groups defined by step or triangular ramp of currents with the exception of transient firing patterns. Our data support the idea that a switch in the electrical properties of lumbar motoneurons might exist in the second postnatal week

  20. Postnatal development of the atlas and axis: CT study

    International Nuclear Information System (INIS)

    Byun, Sung Su; Kim, Hyung Jin; Lim, Myung Kwan; Kim, Won Hong; Jeon, Yong Sun; Kim, Jeong Ho; Kim, Sung Tae

    2003-01-01

    To evaluate normal postnatal development of the atlas and axis by means of CT scanning. We prospectively analyzed CT scans of the developing atlas and axis of 200 normal children aged less than 14, investigating the CT appearance of these regions with particular attenuation to two synchondroses related to the atlas and four synchondroses and one ossification center related to the axis. Fusion varying was categorized as either low (grade1-5) or high (grade4-5), according to the varying degrees of fusion at each synchondrosis of ossification center. Neurocentral synchondrosis of the atlas was low grade in all children less than five, and high grade in all aged nine or more, while posterior synchondrosis of the atlas was low grade in 97% of children less than three and high grade in 99% aged three or more. As for the axis, neurocentral synchondrosis was low grade in all children less than three, and high grade in 97% of children aged five or more. PS of the axis was low grade in both children less than 6 months, and high grade in all aged two years or more. Dentocentral synchondrosis of the axis was low grade in 93% of children less than three and high grade in 96% of those aged at least five. Intradental axial synchondrosis was high grade in all children. Fusion of the terminal ossicle with the remainder of the dens was low in all children less than five and high in 97% of those aged nine of more. CT can help determine the parameters of normal postnatal development of the atlas and axis. A knowledge of normal ossification patterns of these regions may help provide an understanding of developmental anomalies and also help prevent confusion with fractures

  1. Annotation of mammalian primary microRNAs

    Directory of Open Access Journals (Sweden)

    Enright Anton J

    2008-11-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are important regulators of gene expression and have been implicated in development, differentiation and pathogenesis. Hundreds of miRNAs have been discovered in mammalian genomes. Approximately 50% of mammalian miRNAs are expressed from introns of protein-coding genes; the primary transcript (pri-miRNA is therefore assumed to be the host transcript. However, very little is known about the structure of pri-miRNAs expressed from intergenic regions. Here we annotate transcript boundaries of miRNAs in human, mouse and rat genomes using various transcription features. The 5' end of the pri-miRNA is predicted from transcription start sites, CpG islands and 5' CAGE tags mapped in the upstream flanking region surrounding the precursor miRNA (pre-miRNA. The 3' end of the pri-miRNA is predicted based on the mapping of polyA signals, and supported by cDNA/EST and ditags data. The predicted pri-miRNAs are also analyzed for promoter and insulator-associated regulatory regions. Results We define sets of conserved and non-conserved human, mouse and rat pre-miRNAs using bidirectional BLAST and synteny analysis. Transcription features in their flanking regions are used to demarcate the 5' and 3' boundaries of the pri-miRNAs. The lengths and boundaries of primary transcripts are highly conserved between orthologous miRNAs. A significant fraction of pri-miRNAs have lengths between 1 and 10 kb, with very few introns. We annotate a total of 59 pri-miRNA structures, which include 82 pre-miRNAs. 36 pri-miRNAs are conserved in all 3 species. In total, 18 of the confidently annotated transcripts express more than one pre-miRNA. The upstream regions of 54% of the predicted pri-miRNAs are found to be associated with promoter and insulator regulatory sequences. Conclusion Little is known about the primary transcripts of intergenic miRNAs. Using comparative data, we are able to identify the boundaries of a significant proportion of

  2. Effects of prenatal X-irradiation on the 14th-18th days of gestation on postnatal growth and development in the rat

    International Nuclear Information System (INIS)

    Jensh, R.P.; Brent, R.L.

    1988-01-01

    Thirty-nine pregnant adult Wistar strain rats were randomly assigned to one of three exposure groups: 0, 0.75, or 1.50 Gy X-radiation total exposure. Animals were exposed from the 14th to the 18th days of gestation at 0, 0.15, or 0.30 Gy per day. At term, 15 rats were killed and morphologic analyses were completed. Twenty-four rats were allowed to deliver their offspring. On the first day of postnatal life, litters were reduced to a maximum of eight pups per litter, with equal numbers of male and female offspring wherever possible. A total of 187 pups were observed for the age of acquisition of five reflexes (air righting, surface righting, visual placing, negative geotaxis, auditory startle) and the appearance of four physiologic markers (pinna detachment, eye opening, vaginal opening, testes descent). There was significant dose-related weight reduction in term fetuses and offspring throughout the 86-day postnatal period. Postnatal growth rate (g gained/day) was unaffected. Adult offspring brain and gonadal weight and organ weight:body weight ratios were reduced. Using the PAC50 methodology, dose-related alterations occurred in the acquisition of several reflexes. All physiologic markers exhibited a dose-related delay in appearance. These results indicate that fractionated exposure to X-radiation during the fetal period in the rat results in dose-dependent alterations in postnatal growth and physiologic development. These studies are important for our understanding of the long-range effects of prenatal exposure to ionizing radiation late in gestation

  3. Prenatal, perinatal and postnatal factors associated with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Imen Hadjkacem

    2016-11-01

    Full Text Available Objective: To identify prenatal, perinatal and postnatal risk factors in children with autism spectrum disorder (ASD by comparing them to their siblings without autistic disorders. Method: The present study is cross sectional and comparative. It was conducted over a period of three months (July–September 2014. It included 101 children: 50 ASD's children diagnosed according to DSM-5 criteria and 51 unaffected siblings. The severity of ASD was assessed by the CARS. Results: Our study revealed a higher prevalence of prenatal, perinatal and postnatal factors in children with ASD in comparison with unaffected siblings. It showed also a significant association between perinatal and postnatal factors and ASD (respectively p = 0.03 and p = 0.042. In this group, perinatal factors were mainly as type of suffering acute fetal (26% of cases, long duration of delivery and prematurity (18% of cases for each factor, while postnatal factors were represented principally by respiratory infections (24%. As for parental factors, no correlation was found between advanced age of parents at the moment of the conception and ASD. Likewise, no correlation was observed between the severity of ASD and different factors. After logistic regression, the risk factors retained for autism in the final model were: male gender, prenatal urinary tract infection, acute fetal distress, difficult labor and respiratory infection. Conclusions: The present survey confirms the high prevalence of prenatal, perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors (acute fetal distress and difficult labor, among others, as determinant variables for the genesis of ASD. Resumo: Objetivo: Identificar fatores de risco pré-natal, perinatal e pós-natal em crianças com transtorno do espectro do autismo (TEA ao compará-las a irmãos sem transtornos de autismo. Método: Este estudo é transversal e comparativo. Ele foi conduzido em um per

  4. 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

  5. Origins and Impacts of New Mammalian Exons

    Directory of Open Access Journals (Sweden)

    Jason J. Merkin

    2015-03-01

    Full Text Available Mammalian genes are composed of exons, but the evolutionary origins and functions of new internal exons are poorly understood. Here, we analyzed patterns of exon gain using deep cDNA sequencing data from five mammals and one bird, identifying thousands of species- and lineage-specific exons. Most new exons derived from unique rather than repetitive intronic sequence. Unlike exons conserved across mammals, species-specific internal exons were mostly located in 5′ UTRs and alternatively spliced. They were associated with upstream intronic deletions, increased nucleosome occupancy, and RNA polymerase II pausing. Genes containing new internal exons had increased gene expression, but only in tissues in which the exon was included. Increased expression correlated with the level of exon inclusion, promoter proximity, and signatures of cotranscriptional splicing. Altogether, these findings suggest that increased splicing at the 5′ ends of genes enhances expression and that changes in 5′ end splicing alter gene expression between tissues and between species.

  6. Imaging intraflagellar transport in mammalian primary cilia.

    Science.gov (United States)

    Besschetnova, Tatiana Y; Roy, Barnali; Shah, Jagesh V

    2009-01-01

    The primary cilium is a specialized organelle that projects from the surface of many cell types. Unlike its motile counterpart it cannot beat but does transduce extracellular stimuli into intracellular signals and acts as a specialized subcellular compartment. The cilium is built and maintained by the transport of proteins and other biomolecules into and out of this compartment. The trafficking machinery for the cilium is referred to as IFT or intraflagellar transport. It was originally identified in the green algae Chlamydomonas and has been discovered throughout the evolutionary tree. The IFT machinery is widely conserved and acts to establish, maintain, and disassemble cilia and flagella. Understanding the role of IFT in cilium signaling and regulation requires a methodology for observing it directly. Here we describe current methods for observing the IFT process in mammalian primary cilia through the generation of fluorescent protein fusions and their expression in ciliated cell lines. The observation protocol uses high-resolution time-lapse microscopy to provide detailed quantitative measurements of IFT particle velocities in wild-type cells or in the context of genetic or other perturbations. Direct observation of IFT trafficking will provide a unique tool to dissect the processes that govern cilium regulation and signaling. 2009 Elsevier Inc. All rights reserved.

  7. DNA synthesis in irradiated mammalian cells

    International Nuclear Information System (INIS)

    Painter, R.B.; California Univ., San Francisco; Young, B.R.

    1987-01-01

    One of the first responses observed in S phase mammalian cells that have suffered DNA damage is the inhibition of initiation of DNA replicons. In cells exposed to ionizing radiation, a single-strand break appears to be the stimulus for this effect, whereby the initiation of many adjacent replicons (a replicon cluster) is blocked by a single-strand break in any one of them. In cells exposed to ultraviolet light (u.v.), replicon initiation is blocked at fluences that induce about one pyrimidine dimer per replicon. The inhibition of replicon initiation by u.v. in Chinese hamster cells that are incapable of excising pyrimidine dimers from their DNA is virtually the same as in cells that are proficient in dimer excision. Therefore, a single-strand break formed during excision repair of pyrimidine dimers is not the stimulus for inhibition of replicon initiation in u.v.-irradiated cells. Considering this fact, as well as the comparative insensitivity of human ataxia telangiectasia cells to u.v.-induced inhibition of replicon initiation, we propose that a relatively rare lesion is the stimulus for u.v. -induced inhibition of replicon initiation. (author

  8. Radiation- induced aneuploidy in mammalian germ cells

    International Nuclear Information System (INIS)

    Tease, C.

    1989-01-01

    The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

  9. Apoptosis in mammalian oocytes: a review.

    Science.gov (United States)

    Tiwari, Meenakshi; Prasad, Shilpa; Tripathi, Anima; Pandey, Ashutosh N; Ali, Irfan; Singh, Arvind K; Shrivastav, Tulsidas G; Chaube, Shail K

    2015-08-01

    Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals.

  10. Protection of cultured mammalian cells by rebamipide

    Energy Technology Data Exchange (ETDEWEB)

    Antoku, Shigetoshi; Aramaki, Ryoji [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine; Tanaka, Hisashi; Kusumoto, Naotoshi

    1997-06-01

    Rebamipide which is used as a drug for gastritis and stomach ulcer has large capability for OH radical scavenging. It is expected that rebamipide has protective effect against ionizing radiations. The present paper deals with protective effect of rebamipide for cultured mammalian cells exposed to ionizing radiations. As rebamipide is insoluble in water, three solvents were used to dissolve. Rebamipide dissolved in dimethyl sulfoxide (DMSO), dimethyl formamide (DMFA) and 0.02 N NaOH was added to the cells in Eagle`s minimum essential medium (MEM) supplemented with 10% fetal calf serum and the cells were irradiated with X-rays. After irradiation, the cells were trypsinized, plated in MEM with 10% fetal calf serum and incubated for 7 days in a CO{sub 2} incubator to form colonies. Rebamipide dissolved in 0.02 N NaOH exhibited the protective effect expected its OH radical scavenging capability. However, the protective effect of rebamipide dissolved in DMSO was about half of that expected by its radical scavenging capability and that of rebamipide dissolved in DMFA was not observed. Uptake of rebamipide labeled with {sup 14}C increased with increasing contact time with rebamipide. These rebamipide mainly distributed in nucleus rather than cytoplasm. (author)

  11. Mammalian oocyte growth and development in vitro.

    Science.gov (United States)

    Eppig, J J; O'Brien, M; Wigglesworth, K

    1996-06-01

    This paper is a review of the current status of technology for mammalian oocyte growth and development in vitro. It compares and contrasts the characteristics of the various culture systems that have been devised for the culture of either isolated preantral follicles or the oocyte-granulosa cell complexes form preantral follicles. The advantages and disadvantages of these various systems are discussed. Endpoints for the evaluation of oocyte development in vitro, including oocyte maturation and embryogenesis, are described. Considerations for the improvement of the culture systems are also presented. These include discussions of the possible effects of apoptosis and inappropriate differentiation of oocyte-associated granulosa cells on oocyte development. Finally, the potential applications of the technology for oocyte growth and development in vitro are discussed. For example, studies of oocyte development in vitro could help to identify specific molecules produced during oocyte development that are essential for normal early embryogenesis and perhaps recognize defects leading to infertility or abnormalities in embryonic development. Moreover, the culture systems may provide the methods necessary to enlarge the populations of valuable agricultural, pharmaceutical product-producing, and endangered animals, and to rescue the oocytes of women about to undergo clinical procedures that place oocytes at risk.

  12. A rule of thumb in mammalian herbivores?

    Science.gov (United States)

    Augner; Provenza; Villalba

    1998-08-01

    In two experiments on appetitive learning we conditioned lambs, Ovis aries, to particular concentrations of a flavour by mixing the flavour with an energy-rich food that complemented their energy-poor diet. The lambs were subsequently offered energy-rich food with five different concentrations of the flavour (the concentration to which they were conditioned, two higher concentrations, and two lower concentrations). At these tests, the lambs consistently preferred the weaker flavours. This finding stands in contrast to earlier results on generalization gradients. In a third experiment, similarly designed to the other two, we tested for effects of a strong flavour on the behaviour of lambs when they were offered a novel nutritious food. Half of the lambs were offered unadulterated wheat, and the others strongly flavoured wheat. We found that the flavour in itself was initially aversive. We propose that the lambs' avoidance of foods with strong flavours may be an expression of a rule of thumb of the type 'given a choice, avoid food with strong flavours'. Such a rule could be part of a risk-averse foraging strategy displayed by mammalian herbivores, and which could be of particular importance when they encounter unfamiliar foods. Copyright 1998 The Association for the Study of Animal Behaviour

  13. Functional Amyloid Formation within Mammalian Tissue.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available Amyloid is a generally insoluble, fibrous cross-beta sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin-a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology.

  14. Repair of radiation damage in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  15. Protection of cultured mammalian cells by rebamipide

    International Nuclear Information System (INIS)

    Antoku, Shigetoshi; Aramaki, Ryoji; Tanaka, Hisashi; Kusumoto, Naotoshi.

    1997-01-01

    Rebamipide which is used as a drug for gastritis and stomach ulcer has large capability for OH radical scavenging. It is expected that rebamipide has protective effect against ionizing radiations. The present paper deals with protective effect of rebamipide for cultured mammalian cells exposed to ionizing radiations. As rebamipide is insoluble in water, three solvents were used to dissolve. Rebamipide dissolved in dimethyl sulfoxide (DMSO), dimethyl formamide (DMFA) and 0.02 N NaOH was added to the cells in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum and the cells were irradiated with X-rays. After irradiation, the cells were trypsinized, plated in MEM with 10% fetal calf serum and incubated for 7 days in a CO 2 incubator to form colonies. Rebamipide dissolved in 0.02 N NaOH exhibited the protective effect expected its OH radical scavenging capability. However, the protective effect of rebamipide dissolved in DMSO was about half of that expected by its radical scavenging capability and that of rebamipide dissolved in DMFA was not observed. Uptake of rebamipide labeled with 14 C increased with increasing contact time with rebamipide. These rebamipide mainly distributed in nucleus rather than cytoplasm. (author)

  16. Angiogenesis is inhibitory for mammalian digit regeneration

    Science.gov (United States)

    Yu, Ling; Yan, Mingquan; Simkin, Jennifer; Ketcham, Paulina D.; Leininger, Eric; Han, Manjong

    2014-01-01

    Abstract The regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti‐angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka, K. (2010). BMP signaling induces digit regeneration in neonatal mice. Development, 137, 551–559). Here we show that during regeneration Vegfa transcripts are not detected in the blastema but are expressed at the onset of differentiation. Treating the amputation wound with vascular endothelial growth factor enhances angiogenesis but inhibits regeneration. We next tested bone morphogenetic protein 9 (BMP9), another known mediator of angiogenesis, and found that BMP9 is also a potent inhibitor of digit tip regeneration. BMP9 induces Vegfa expression in the digit stump suggesting that regenerative failure is mediated by enhanced angiogenesis. Finally, we show that BMP9 inhibition of regeneration is completely rescued by treatment with pigment epithelium‐derived factor. These studies show that precocious angiogenesis is inhibitory for regeneration, and provide compelling evidence that the regulation of angiogenesis is a critical factor in designing therapies aimed at stimulating mammalian regeneration. PMID:27499862

  17. Functional amyloid formation within mammalian tissue.

    Directory of Open Access Journals (Sweden)

    Douglas M Fowler

    2006-01-01

    Full Text Available Amyloid is a generally insoluble, fibrous cross-beta sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin-a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology.

  18. Mitochondrial dynamics in mammalian health and disease.

    Science.gov (United States)

    Liesa, Marc; Palacín, Manuel; Zorzano, Antonio

    2009-07-01

    The meaning of the word mitochondrion (from the Greek mitos, meaning thread, and chondros, grain) illustrates that the heterogeneity of mitochondrial morphology has been known since the first descriptions of this organelle. Such a heterogeneous morphology is explained by the dynamic nature of mitochondria. Mitochondrial dynamics is a concept that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial architecture (morphology and distribution), and connectivity mediated by tethering and fusion/fission events. The relevance of these events in mitochondrial and cell physiology has been partially unraveled after the identification of the genes responsible for mitochondrial fusion and fission. Furthermore, during the last decade, it has been identified that mutations in two mitochondrial fusion genes (MFN2 and OPA1) cause prevalent neurodegenerative diseases (Charcot-Marie Tooth type 2A and Kjer disease/autosomal dominant optic atrophy). In addition, other diseases such as type 2 diabetes or vascular proliferative disorders show impaired MFN2 expression. Altogether, these findings have established mitochondrial dynamics as a consolidated area in cellular physiology. Here we review the most significant findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies.

  19. Repair of radiation damage in mammalian cells

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis

  20. A hybrid mammalian cell cycle model

    Directory of Open Access Journals (Sweden)

    Vincent Noël

    2013-08-01

    Full Text Available Hybrid modeling provides an effective solution to cope with multiple time scales dynamics in systems biology. Among the applications of this method, one of the most important is the cell cycle regulation. The machinery of the cell cycle, leading to cell division and proliferation, combines slow growth, spatio-temporal re-organisation of the cell, and rapid changes of regulatory proteins concentrations induced by post-translational modifications. The advancement through the cell cycle comprises a well defined sequence of stages, separated by checkpoint transitions. The combination of continuous and discrete changes justifies hybrid modelling approaches to cell cycle dynamics. We present a piecewise-smooth version of a mammalian cell cycle model, obtained by hybridization from a smooth biochemical model. The approximate hybridization scheme, leading to simplified reaction rates and binary event location functions, is based on learning from a training set of trajectories of the smooth model. We discuss several learning strategies for the parameters of the hybrid model.

  1. Maternal Postnatal Depression and Anxiety and Their Association with Child Emotional Negativity and Behavior Problems at Two Years

    Science.gov (United States)

    Prenoveau, Jason M.; Craske, Michelle G.; West, Valerie; Giannakakis, Andreas; Zioga, Maria; Lehtonen, Annukka; Davies, Beverley; Netsi, Elena; Cardy, Jessica; Cooper, Peter; Murray, Lynne; Stein, Alan

    2017-01-01

    Postnatal maternal depression is associated with poorer child emotional and behavioral functioning, but it is unclear whether this occurs following brief episodes or only with persistent depression. Little research has examined the relation between postnatal anxiety and child outcomes. The present study examined the role of postnatal major…

  2. 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.

  3. Transient overexposure of neuregulin 3 during early postnatal development impacts selective behaviors in adulthood.

    Directory of Open Access Journals (Sweden)

    Clare Paterson

    Full Text Available Neuregulin 3 (NRG3, a specific ligand for ErbB4 and a neuronal-enriched neurotrophin is implicated in the genetic predisposition to a broad spectrum of neurodevelopmental, neurocognitive and neuropsychiatric disorders, including Alzheimer's disease, autism and schizophrenia. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, accompanied by increased expression of prefrontal cortical NRG3. Despite our expanding knowledge of genetic involvement of NRG3 in neurological disorders, little is known about the neurodevelopmental mechanisms of risk. Here we exploited the fact that a paralog of NRG3, NRG1, readily penetrates the murine blood brain barrier (BBB. In this study we synthesized the bioactive epidermal growth factor (EGF domain of NRG3, and using previously validated in-vivo peripheral injection methodologies in neonatal mice, demonstrate that NRG3 successfully crosses the BBB, where it activates its receptor ErbB4 and downstream Akt signaling at levels of bioactivity comparable to NRG1. To determine the impact of NRG3 overexpression during one critical developmental window, C57BL/6 male mice were subcutaneously injected daily with NRG1-EGF, NRG3-EGF or vehicle from postnatal days 2-10. Mice were tested in adulthood using a comprehensive battery of behavioral tasks relevant to neurocognitive and psychiatric disorders. In agreement with previous studies, developmental overexposure to NRG1 induced multiple non-CNS mediated peripheral effects as well as severely disrupting performance of prepulse inhibition of the startle response. In contrast, NRG3 had no effect on any peripheral measures investigated or sensorimotor gating. Specifically, developmental NRG3 overexposure produced an anxiogenic-like phenotype and deficits in social behavior in adulthood. These results provide primary data to support a role for NRG3 in brain development and function, which appears to

  4. The evolution of intelligence in mammalian carnivores.

    Science.gov (United States)

    Holekamp, Kay E; Benson-Amram, Sarah

    2017-06-06

    Although intelligence should theoretically evolve to help animals solve specific types of problems posed by the environment, it is unclear which environmental challenges favour enhanced cognition, or how general intelligence evolves along with domain-specific cognitive abilities. The social intelligence hypothesis posits that big brains and great intelligence have evolved to cope with the labile behaviour of group mates. We have exploited the remarkable convergence in social complexity between cercopithecine primates and spotted hyaenas to test predictions of the social intelligence hypothesis in regard to both cognition and brain size. Behavioural data indicate that there has been considerable convergence between primates and hyaenas with respect to their social cognitive abilities. Moreover, compared with other hyaena species, spotted hyaenas have larger brains and expanded frontal cortex, as predicted by the social intelligence hypothesis. However, broader comparative study suggests that domain-general intelligence in carnivores probably did not evolve in response to selection pressures imposed specifically in the social domain. The cognitive buffer hypothesis, which suggests that general intelligence evolves to help animals cope with novel or changing environments, appears to offer a more robust explanation for general intelligence in carnivores than any hypothesis invoking selection pressures imposed strictly by sociality or foraging demands.

  5. Cyanotoxins at low doses induce apoptosis and inflammatory effects in murine brain cells: Potential implications for neurodegenerative diseases

    OpenAIRE

    Takser, Larissa; Benachour, Nora; Husk, Barry; Cabana, Hubert; Gris, Denis

    2016-01-01

    Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study investigated whether mammalian brain and immune cells can be a target of certain cyanotoxins, at doses approximating those in the guideline levels for drinking water, either alone or in mixtures. We examined the effects on cellular viability, apoptosis and inflammation signalling of several toxins on murine macrophage-like ...

  6. Inequities in maternal postnatal visits among public and private patients: 2004 Pelotas cohort study

    Directory of Open Access Journals (Sweden)

    Marco Paula L

    2009-09-01

    Full Text Available Abstract Background The postnatal period is the ideal time to deliver interventions to improve the health of both the newborn and the mother. However, postnatal care shows low-level coverage in a large number of countries. The objectives of this study were to: 1 investigate inequities in maternal postnatal visits, 2 examine differences in postnatal care coverage between public and private providers and 3 explore the relationship between the absence of maternal postnatal visits and exclusive breastfeeding, use of contraceptive methods and maternal smoking three months after birth. Methods In the calendar year of 2004 a birth cohort study was started in the city of Pelotas, Brazil. Mothers were interviewed soon after delivery and at three months after birth. The absence of postnatal visits was defined as having no consultations between the time of hospital discharge and the third month post-partum. Logistic regression analysis was used to estimate the association between absence of postnatal visits and type of insurance scheme adjusting for potential confounding factors. Results Poorer women, black/mixed, those with lower level of education, single mothers, adolescents, multiparae, smokers, women who delivered vaginally and those who were not assisted by a physician were less likely to attend postnatal care. Postnatal visits were also less frequent among women who relied in the public sector than among private patients (72.4% vs 96% among public and private patients, respectively, x2 p Conclusion Postpartum care is available for every woman free of charge in the Brazilian Publicly-funded health care system. However, low levels of postpartum care were seen in the study (77%. Efforts should be made to increase the percentage of women receiving postpartum care, particularly those in socially disadvantaged groups. This could include locally-adapted health education interventions that address women's beliefs and attitudes towards postpartum care. There

  7. Antenatal hydronephrosis: Negative predictive value of normal postnatal ultrasound - a 5-year study

    Energy Technology Data Exchange (ETDEWEB)

    Moorthy, I.; Joshi, N.; Cook, J.V. E-mail: jcook@epsom-sthelier.nhs.uk; Warren, M

    2003-12-01

    AIM: To determine whether normal postnatal ultrasound, as part of a strict screening protocol for the detection and follow-up of antenatal hydronephrosis, effectively excludes the majority of babies with congenital urinary tract abnormalities that would otherwise present with a urinary tract infection. MATERIALS AND METHODS: We retrospectively reviewed all babies who had postnatal follow-up of antenatally detected hydronephrosis over a 5-year period at our institution, a district general Trust with a specialist paediatric unit. We then studied all babies presenting with urinary tract infection before their first birthday to our institution over the same period. By cross-referencing these two study groups we were able to determine which babies developed a urinary tract infection having been previously discharged after normal postnatal ultrasound. RESULTS: Four hundred and twenty-five babies had postnatal follow-up of antenatal hydronephrosis. Of these, 284 were investigated with ultrasound alone. In the same 5-year period, 230 babies presented with urinary tract infection before their first birthday. Only three of these babies had been previously discharged after normal postnatal ultrasound. The negative predictive value of a normal postnatal ultrasound was therefore 98.9% (281/284) for babies who subsequently presented with a urinary tract infection before their first birthday. CONCLUSION: Careful antenatal and postnatal ultrasound with strict protocols is effective in detecting congenital renal tract abnormalities. Infants discharged after normal postnatal ultrasound are highly unlikely to still have an undetected urinary tract abnormality. We suggest that all babies with antenatal hydronephrosis are started on prophylactic antibiotics at birth, pending further investigation. All babies without features of severe obstruction antenatally should have their postnatal ultrasound delayed for a month. We recommend selective use of micturating cystourethrogram (MCUG

  8. Antenatal hydronephrosis: Negative predictive value of normal postnatal ultrasound - a 5-year study

    International Nuclear Information System (INIS)

    Moorthy, I.; Joshi, N.; Cook, J.V.; Warren, M.

    2003-01-01

    AIM: To determine whether normal postnatal ultrasound, as part of a strict screening protocol for the detection and follow-up of antenatal hydronephrosis, effectively excludes the majority of babies with congenital urinary tract abnormalities that would otherwise present with a urinary tract infection. MATERIALS AND METHODS: We retrospectively reviewed all babies who had postnatal follow-up of antenatally detected hydronephrosis over a 5-year period at our institution, a district general Trust with a specialist paediatric unit. We then studied all babies presenting with urinary tract infection before their first birthday to our institution over the same period. By cross-referencing these two study groups we were able to determine which babies developed a urinary tract infection having been previously discharged after normal postnatal ultrasound. RESULTS: Four hundred and twenty-five babies had postnatal follow-up of antenatal hydronephrosis. Of these, 284 were investigated with ultrasound alone. In the same 5-year period, 230 babies presented with urinary tract infection before their first birthday. Only three of these babies had been previously discharged after normal postnatal ultrasound. The negative predictive value of a normal postnatal ultrasound was therefore 98.9% (281/284) for babies who subsequently presented with a urinary tract infection before their first birthday. CONCLUSION: Careful antenatal and postnatal ultrasound with strict protocols is effective in detecting congenital renal tract abnormalities. Infants discharged after normal postnatal ultrasound are highly unlikely to still have an undetected urinary tract abnormality. We suggest that all babies with antenatal hydronephrosis are started on prophylactic antibiotics at birth, pending further investigation. All babies without features of severe obstruction antenatally should have their postnatal ultrasound delayed for a month. We recommend selective use of micturating cystourethrogram (MCUG

  9. Does autophagy have a license to kill mammalian cells?

    NARCIS (Netherlands)

    Scarlatti, F.; Granata, R.; Meijer, A. J.; Codogno, P.

    2009-01-01

    Macroautophagy is an evolutionarily conserved vacuolar, self-digesting mechanism for cellular components, which end up in the lysosomal compartment. In mammalian cells, macroautophagy is cytoprotective, and protects the cells against the accumulation of damaged organelles or protein aggregates, the

  10. Genetic Analysis of a Mammalian Chromosomal Origin of Replication

    National Research Council Canada - National Science Library

    Altman, Amy

    2001-01-01

    The main goal of the research proposal was to develop an assay system for studying the specific genetic elements, if any, involved in the initiation of DNA replication in mammalian cells as outlined in Task 1...

  11. Repair of furocoumarin adducts in mammalian cells

    International Nuclear Information System (INIS)

    Zolan, M.E.; Smith, C.A.; Hanawalt, P.C.

    1984-01-01

    DNA repair was studied in cultured mammalian cells treated with the furocoumarins 8-methoxypsoralen (8-MOP), aminomethyl trioxsalen, or angelicin and irradiated with near UV light. The amount of DNA cross-linked by 8-MOP in normal human cells decreased by about one-half in 24 hours after treatment; no decrease was observed in xeroderma pigmentosum cells, group A. At present, it is not known to what extent this decrease represents complete repair events at the sites of cross-links. Furocoumarin adducts elicited excision repair in normal human and monkey cells but not in xeroderma pigmentosum group A cells. This excision repair resembled in several aspects that elicited by pyrimidine dimers, formed in DNA by irradiation with 254-nm UV light; however, it appeared that for at least 8-MOP and aminomethyl trioxsalen, removal of adducts was not as efficient as was the removal of pyrimidine dimers. A comparison was also made of repair in the 172-base-pair repetitive alpha-DNA component of monkey cells to repair in the bulk of the genome. Although repair elicited by pyrimidine dimers in alpha-DNA was the same as in the bulk DNA, that following treatment of cells with either aminomethyl trioxsalen or angelicin and near UV was markedly deficient in alpha-DNA. This deficiency reflected the removal of fewer adducts from alpha-DNA after the same initial adduct frequencies. These results could mean that each furocoumarin may produce several structurally distinct adducts to DNA in cells and that the capacity of cellular repair systems to remove these various adducts may vary greatly

  12. Acidic mammalian chitinase in dry eye conditions.

    Science.gov (United States)

    Musumeci, Maria; Aragona, Pasquale; Bellin, Milena; Maugeri, Francesco; Rania, Laura; Bucolo, Claudio; Musumeci, Salvatore

    2009-07-01

    An acidic mammalian chitinase (AMCase) seems to be implicated in allergic asthma and allergic ocular pathologies. The aim of this work was to investigate the role of AMCase during Sjögren's Syndrome (SS) and Meibomian Gland Dysfunction (MGD) dry eye diseases. Six patients with MGD dry eye (20-58 years, median 40) and six patients with dry eye associated to SS (32-60 years, median 47) were enrolled in this study. AMCase activity was measured in tears and AMCase mRNA expression was evaluated by real-time polymerase chain reaction from RNA extracted from epithelial cells of the conjunctiva. Six healthy adult subjects of the same age (34-44 years, median 39) were also studied as the control group. AMCase activity was significantly increased in patients affected by MGD dry eye (18.54 +/- 1.5 nmol/ml/h) and SS dry eye (8.94 +/- 1.0 nmol/ml/h) respectively, compared to healthy controls (1.6 +/- 0.2 nmol/ml/h). AMCase activity was higher in the tears of subjects with MGD dry eye (P < 0.001). AMCase mRNA was detected in conjunctival epithelial cells and the expression was significantly higher in MGD dry eye than SS dry eye. A significant correlation between AMCase activity in the tears and mRNA in conjunctival epithelial cells was found. AMCase may be an important marker in the pathogenesis of dry eye, suggesting the potential role of AMCase as a therapeutic target in these frequent pathologies.

  13. Assays for mammalian tyrosinase: a comparative study

    International Nuclear Information System (INIS)

    Jara, J.R.; Solano, F.; Lozano, J.A.

    1988-01-01

    This work describes a comparative study of the tyrosinase activity determined using three methods which are the most extensively employed; two radiometric assays using L-tyrosine as substrate (tyrosine hydroxylase and melanin formation activities) and one spectrophotometric assay using L-dopa (dopa oxidase activity). The three methods were simultaneously employed to measure the activities of the soluble, melanosomal, and microsomal tyrosinase isozymes from Harding-Passey mouse melanoma through their purification processes. The aim of this study was to find any correlation among the tyrosinase activities measured by the three different assays and to determine whether that correlation varied with the isozyme and its degree of purification. The results show that mammalian tyrosinase has a greater turnover number for L-dopa than for L-tyrosine. Thus, enzyme activity, expressed as mumol of substrate transformed per min, is higher in assays using L-dopa as substrate than those using L-tyrosine. Moreover, the percentage of hydroxylated L-tyrosine that is converted into melanin is low and is affected by several factors, apparently decreasing the tyrosinase activity measured by the melanin formation assay. Bearing these considerations in mind, average interassay factors are proposed. Their values are 10 to transform melanin formation into tyrosine hydroxylase activity, 100 to transform tyrosine hydroxylase into dopa oxidase activity, and 1,000 to transform melanin formation into dopa oxidase activity. Variations in these values due to the presence in the tyrosinase preparations of either inhibitors or regulatory factors in melanogenesis independent of tyrosinase are also discussed

  14. Mammalian play: training for the unexpected.

    Science.gov (United States)

    Spinka, M; Newberry, R C; Bekoff, M

    2001-06-01

    In this review, we present a new conceptual framework for the study of play behavior, a hitherto puzzling array of seemingly purposeless and unrelated behavioral elements that are recognizable as play throughout the mammalian lineage. Our major new functional hypothesis is that play enables animals to develop flexible kinematic and emotional responses to unexpected events in which they experience a sudden loss of control. Specifically, we propose that play functions to increase the versatility of movements used to recover from sudden shocks such as loss of balance and falling over, and to enhance the ability of animals to cope emotionally with unexpected stressful situations. To obtain this "training for the unexpected," we suggest that animals actively seek and create unexpected situations in play through self-handicapping; that is, deliberately relaxing control over their movements or actively putting themselves into disadvantageous positions and situations. Thus, play is comprised of sequences in which the players switch rapidly between well-controlled movements similar to those used in "serious" behavior and self-handicapping movements that result in temporary loss of control. We propose that this playful switching between in-control and out-of-control elements is cognitively demanding, setting phylogenetic and ontogenetic constraints on play, and is underlain by neuroendocrinological responses that produce a complex emotional state known as "having fun." Furthermore, we propose that play is often prompted by relatively novel or unpredictable stimuli, and is thus related to, although distinct from, exploration. We present 24 predictions that arise from our new theoretical framework, examining the extent to which they are supported by the existing empirical evidence and contrasting them with the predictions of four major alternative hypotheses about play. We argue that our "training for the unexpected" hypothesis can account for some previously puzzling

  15. Fueling and Imaging Brain Activation

    Directory of Open Access Journals (Sweden)

    Gerald A Dienel

    2012-05-01

    Full Text Available Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron–astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models.

  16. Fueling and imaging brain activation

    Science.gov (United States)

    Dienel, Gerald A

    2012-01-01

    Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron–astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861

  17. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    Science.gov (United States)

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

  18. Role of cyclins in controlling progression of mammalian spermatogenesis

    OpenAIRE

    WOLGEMUTH, DEBRA J.; MANTEROLA, MARCIA; VASILEVA, ANA

    2013-01-01

    Cyclins are key regulators of the mammalian cell cycle, functioning primarily in concert with their catalytic partners, the cyclin-dependent kinases (Cdks). While their function during mitosis in somatic cells has been extensively documented, their function during both mitosis and meiosis in the germ line is poorly understood. From the perspective of cell cycle regulation there are several aspects of mammalian spermatogenesis that suggest unique modes of regulation and hence, possible unique ...

  19. Evaluation of Mammalian Interspersed Repeats to investigate the goat genome

    Directory of Open Access Journals (Sweden)

    P. Mariani

    2010-01-01

    Full Text Available Among the repeated sequences present in most eukaryotic genomes, SINEs (Short Interspersed Nuclear Elements are widely used to investigate evolution in the mammalian order (Buchanan et al., 1999. One family of these repetitive sequences, the MIR (Mammalian Interspersed Repeats; Jurka et al., 1995, is ubiquitous in all mammals.MIR elements are tRNA-derived SINEs and are identifiable by a conserved core region of about 70 nucleotides.

  20. An Analytical Study of Mammalian Bite Wounds Requiring Inpatient Management

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    Young-Geun Lee

    2013-11-01

    Full Text Available BackgroundMammalian bite injuries create a public health problem because of their frequency, potential severity, and increasing number. Some researchers have performed fragmentary analyses of bite wounds caused by certain mammalian species. However, little practical information is available concerning serious mammalian bite wounds that require hospitalization and intensive wound management. Therefore, the purpose of this study was to perform a general review of serious mammalian bite wounds.MethodsWe performed a retrospective review of the medical charts of 68 patients who were referred to our plastic surgery department for the treatment of bite wounds between January 2003 and October 2012. The cases were analyzed according to the species, patient demographics, environmental factors, injury characteristics, and clinical course.ResultsAmong the 68 cases of mammalian bite injury, 58 (85% were caused by dogs, 8 by humans, and 2 by cats. Most of those bitten by a human and both of those bitten by cats were male. Only one-third of all the patients were children or adolescents. The most frequent site of injury was the face, with 40 cases, followed by the hand, with 16 cases. Of the 68 patients, 7 were treated with secondary intention healing. Sixty-one patients underwent delayed procedures, including delayed direct closure, skin graft, composite graft, and local flap.ConclusionsBased on overall findings from our review of the 68 cases of mammalian bites, we suggest practical guidelines for the management of mammalian bite injuries, which could be useful in the treatment of serious mammalian bite wounds.