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

Science.gov (United States)

Sun, Lina; Sun, Qingshan; Qi, Jinshun

2017-10-26

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

Linking adult olfactory neurogenesis to social behavior

Directory of Open Access Journals (Sweden)

Claudia E Feierstein

2012-11-01

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

Detrimental role of prolonged sleep deprivation on adult neurogenesis

Directory of Open Access Journals (Sweden)

Carina eFernandes

2015-04-01

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

56Fe particle exposure results in a long-lasting increase in a cellular index of genomic instability and transiently suppresses adult hippocampal neurogenesis in vivo

Science.gov (United States)

DeCarolis, Nathan A.; Rivera, Phillip D.; Ahn, Francisca; Amaral, Wellington Z.; LeBlanc, Junie A.; Malhotra, Shveta; Shih, Hung-Ying; Petrik, David; Melvin, Neal R.; Chen, Benjamin P. C.; Eisch, Amelia J.

2014-07-01

The high-LET HZE particles from galactic cosmic radiation pose tremendous health risks to astronauts, as they may incur sub-threshold brain injury or maladaptations that may lead to cognitive impairment. The health effects of HZE particles are difficult to predict and unfeasible to prevent. This underscores the importance of estimating radiation risks to the central nervous system as a whole as well as to specific brain regions like the hippocampus, which is central to learning and memory. Given that neurogenesis in the hippocampus has been linked to learning and memory, we investigated the response and recovery of neurogenesis and neural stem cells in the adult mouse hippocampal dentate gyrus after HZE particle exposure using two nestin transgenic reporter mouse lines to label and track radial glia stem cells (Nestin-GFP and Nestin-CreERT2/R26R:YFP mice, respectively). Mice were subjected to 56Fe particle exposure (0 or 1 Gy, at either 300 or 1000 MeV/n) and brains were harvested at early (24 h), intermediate (7 d), and/or long time points (2-3 mo) post-irradiation. 56Fe particle exposure resulted in a robust increase in 53BP1+ foci at both the intermediate and long time points post-irradiation, suggesting long-term genomic instability in the brain. However, 56Fe particle exposure only produced a transient decrease in immature neuron number at the intermediate time point, with no significant decrease at the long time point post-irradiation. 56Fe particle exposure similarly produced a transient decrease in dividing progenitors, with fewer progenitors labeled at the early time point but equal number labeled at the intermediate time point, suggesting a recovery of neurogenesis. Notably, 56Fe particle exposure did not change the total number of nestin-expressing neural stem cells. These results highlight that despite the persistence of an index of genomic instability, 56Fe particle-induced deficits in adult hippocampal neurogenesis may be transient. These data support

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.

A possible role for the immune system in adult neurogenesis: new insights from an invertebrate model.

Science.gov (United States)

Harzsch, Steffen; von Bohlen Und Halbach, Oliver

2016-04-01

Persistent neurogenesis in the adult brain of both vertebrates and invertebrates was previously considered to be driven by self-renewing neuronal stem cells of ectodermal origin. Recent findings in an invertebrate model challenge this view and instead provide evidence for a recruitment of neuronal precursors from a non-neuronal source. In the brain of adult crayfish, a neurogenic niche was identified that contributes progeny to the adult central olfactory pathway. The niche may function in attracting cells from the hemolymph and transforming them into cells with a neuronal fate. This finding implies that the first-generation neuronal precursors located in the crayfish neurogenic niche are not self-renewing. Evidence is summarized in support of a critical re-evaluation of long-term self-renewal of mammalian neuronal stem cells. Latest findings suggest that a tight link between the immune system and the system driving adult neurogenesis may not only exist in the crayfish but also in mammals. Copyright © 2015 Elsevier GmbH. All rights reserved.

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

Science.gov (United States)

2014-01-01

Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669

Adult hippocampal neurogenesis in natural populations of mammals.

Science.gov (United States)

Amrein, Irmgard

2015-05-01

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

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

Science.gov (United States)

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

2015-01-05

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

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

Science.gov (United States)

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

2017-01-01

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

Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

Directory of Open Access Journals (Sweden)

Lorena Varela-Nallar

2015-01-01

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

Divergent Roles of Central Serotonin in Adult Hippocampal Neurogenesis

Directory of Open Access Journals (Sweden)

Ning-Ning Song

2017-06-01

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

Impaired recruitment of seizure-generated neurons into functional memory networks of the adult dentate gyrus following long-term amygdala kindling.

Science.gov (United States)

Fournier, Neil M; Botterill, Justin J; Marks, Wendie N; Guskjolen, Axel J; Kalynchuk, Lisa E

2013-06-01

Epileptic seizures increase the birth of new neurons in the adult hippocampus. Although the consequences of aberrant neurogenesis on behavior are not fully understood, one hypothesis is that seizure-generated neurons might form faulty circuits that disrupt hippocampal functions, such as learning and memory. In the present study, we employed long-term amygdala kindling (i.e., rats receive 99-electrical stimulations) to examine the effect of repeated seizures on hippocampal neurogenesis and behavior. We labeled seizure-generated cells with the proliferation marker BrdU after 30-stimulations and continued kindling for an additional 4weeks to allow newborn neurons to mature under conditions of repeated seizures. After kindling was complete, rats were tested in a trace fear conditioning task and sacrificed 2h later to examine if 4-week old newborn cells were recruited into circuits involved in the retrieval of emotional memory. Compared to non-kindled controls, long-term kindled rats showed significant impairments in fear memory reflected in a decrease in conditioned freezing to both tone and contextual cues during testing. Moreover, long-term kindling also prevented the activation of 4-week old newborn cells in response to fear memory retrieval. These results indicate that the presence of seizure activity during cell maturation impedes the ability of new neurons to integrate properly into circuits important in memory formation. Together, our findings suggest that aberrant seizure-induced neurogenesis might contribute to the development of learning impairments in chronic epilepsy and raise the possibility that targeting the reduced activation of adult born neurons could represent a beneficial strategy to reverse cognitive deficits in some epileptic patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Adult Neurogenesis and Neurodegenerative Diseases: A Systems Biology Perspective

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

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

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

Science.gov (United States)

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

2015-05-20

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

Tau protein and adult hippocampal neurogenesis

Directory of Open Access Journals (Sweden)

Almudena eFuster-Matanzo

2012-07-01

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

Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function

Science.gov (United States)

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

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

Science.gov (United States)

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

2014-07-01

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

Spatial relational memory requires hippocampal adult neurogenesis.

Directory of Open Access Journals (Sweden)

David Dupret

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

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

Directory of Open Access Journals (Sweden)

He Liu

2016-01-01

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

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

Science.gov (United States)

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

2018-01-08

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

Recent Advances on the Role of Neurogenesis in the Adult Brain: Therapeutic Potential in Parkinson's and Alzheimer's Diseases.

Science.gov (United States)

Radad, Khaled; Moldzio, Rudolf; Al-Shraim, Mubarak; Kranner, Barbara; Krewenka, Christopher; Rausch, Wolf-Dieter

2017-01-01

Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus. These discoveries question a long standing dogma on nervous system regeneration and provide medical science with potential new strategies to harness the process of neurogenesis for treating neurological disabilities and neurodegenerative diseases. In this current review, we address the most recent advances on the role of neurogenesis in the adult brain and therapeutic potential in the two most common neurodegenerative disorders, Parkinson's and Alzheimer's diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Long-Term Memory Performance in Adult ADHD.

Science.gov (United States)

Skodzik, Timo; Holling, Heinz; Pedersen, Anya

2017-02-01

Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

Adult hippocampal neurogenesis reduces memory interference in humans: opposing effects of aerobic exercise and depression

Directory of Open Access Journals (Sweden)

Nicolas eDéry

2013-04-01

Full Text Available Since the remarkable discovery of adult neurogenesis in the mammalian hippocampus, considerable effort has been devoted to unraveling the functional significance of these new neurons. Our group has proposed that a continual turnover of neurons in the DG could contribute to the development of event-unique memory traces that act to reduce interference between highly similar inputs. To test this theory, we implemented a continuous recognition task containing some objects that were repeated across trials as well as some objects that were highly similar, but not identical, to ones previously observed. The similar objects, termed lures, overlap substantially with previously viewed stimuli, and thus, may require hippocampal neurogenesis in order to avoid catastrophic interference. Lifestyle factors such as aerobic exercise and stress have been shown to impact the local neurogenic microenvironment, leading to enhanced and reduced levels of DG neurogenesis, respectively. Accordingly, we hypothesized that healthy young adults who take part in a long-term aerobic exercise regime would demonstrate enhanced performance on the visual pattern separation task, specifically at correctly categorizing lures as similar. Indeed, those who experienced a proportionally large change in fitness demonstrated a significantly greater improvement in their ability to correctly identify lure stimuli as similar. Conversely, we expected that those who score high on depression scales, an indicator of chronic stress, would exhibit selective deficits at appropriately categorizing lures. As expected, those who scored high on the Beck Depression Inventory (BDI were significantly worse than those with relatively lower BDI scores at correctly identifying lures as similar, while performance on novel and repeated stimuli was identical. Taken together, our results support the hypothesis that adult-born neurons in the DG contribute to the orthogonalization of incoming information.

Analysis of neural progenitors from embryogenesis to juvenile adult in Xenopus laevis reveals biphasic neurogenesis and continuous lengthening of the cell cycle

Directory of Open Access Journals (Sweden)

Raphaël Thuret

2015-12-01

Full Text Available Xenopus laevis is a prominent model system for studying neural development, but our understanding of the long-term temporal dynamics of neurogenesis remains incomplete. Here, we present the first continuous description of neurogenesis in X. laevis, covering the entire period of development from the specification of neural ectoderm during gastrulation to juvenile frog. We have used molecular markers to identify progenitors and neurons, short-term bromodeoxyuridine (BrdU incorporation to map the generation of newborn neurons and dual pulse S-phase labelling to characterise changes in their cell cycle length. Our study revealed the persistence of Sox3-positive progenitor cells from the earliest stages of neural development through to the juvenile adult. Two periods of intense neuronal generation were observed, confirming the existence of primary and secondary waves of neurogenesis, punctuated by a period of quiescence before metamorphosis and culminating in another period of quiescence in the young adult. Analysis of multiple parameters indicates that neural progenitors alternate between global phases of differentiation and amplification and that, regardless of their behaviour, their cell cycle lengthens monotonically during development, at least at the population level.

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

Oosthuizen, M K; Amrein, I

2016-06-02

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

Forebrain neurogenesis: From embryo to adult.

Science.gov (United States)

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

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Suk-yu Yau

2014-01-01

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

Adult neurogenesis modifies excitability of the dentate gyrus

Directory of Open Access Journals (Sweden)

Taruna eIkrar

2013-12-01

Full Text Available Adult-born dentate granule neurons contribute to memory encoding functions of the dentate gyrus (DG such as pattern separation. However, local circuit-mechanisms by which adult-born neurons partake in this process are poorly understood. Computational, neuroanatomical and electrophysiological studies suggest that sparseness of activation in the granule cell layer (GCL is conducive for pattern separation. A sparse coding scheme is thought to facilitate the distribution of similar entorhinal inputs across the GCL to decorrelate overlapping representations and minimize interference. Here we used fast voltage-sensitive dye (VSD imaging combined with laser photostimulation and electrical stimulation to examine how selectively increasing adult DG neurogenesis influences local circuit activity and excitability. We show that DG of mice with more adult-born neurons exhibits decreased strength of neuronal activation and more restricted excitation spread in GCL while maintaining effective output to CA3c. Conversely, blockade of adult hippocampal neurogenesis changed excitability of the DG in the opposite direction. Analysis of GABAergic inhibition onto mature dentate granule neurons in the DG of mice with more adult-born neurons shows a modest readjustment of perisomatic inhibitory synaptic gain without changes in overall inhibitory tone, presynaptic properties or GABAergic innervation pattern. Retroviral labeling of connectivity in mice with more adult-born neurons showed increased number of excitatory synaptic contacts of adult-born neurons onto hilar interneurons. Together, these studies demonstrate that adult hippocampal neurogenesis modifies excitability of mature dentate granule neurons and that this non-cell autonomous effect may be mediated by local circuit mechanisms such as excitatory drive onto hilar interneurons. Modulation of DG excitability by adult-born dentate granule neurons may enhance sparse coding in the GCL to influence pattern

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

Directory of Open Access Journals (Sweden)

Valeria Bortolotto

2014-01-01

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

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

Science.gov (United States)

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

2012-09-01

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

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

Directory of Open Access Journals (Sweden)

Valentina Olivera-Pasilio

2017-08-01

. Some newborn cells expressed the mature neuronal marker tyrosine hydroxylase in the subpallium (chase: 90 days and olfactory bulb (chase: 180 days, indicating the acquisition of a mature neuronal phenotype. Long term CldU labeled newborn cells of the granular layer of the corpus cerebelli were also retrogradely labeled “in vivo,” suggesting their insertion into the neural networks. These findings evidence the neurogenic capacity of telencephalic, mesencephalic, and rhombencephalic brain proliferation zones in G. omarorum, supporting the phylogenetic conserved feature of adult neurogenesis and its functional significance.

The impact of cocaine on adult hippocampal neurogenesis: Potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder.

Science.gov (United States)

Castilla-Ortega, Estela; Ladrón de Guevara-Miranda, David; Serrano, Antonia; Pavón, Francisco J; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J

2017-10-01

After discovering that addictive drugs alter adult neurogenesis, the potential role of adult-born hippocampal neurons in drug addiction has become a promising research field, in which cocaine is the most frequently investigated drug. Although a substantial amount of pre-clinical evidence has accumulated, additional studies are required to reveal the mechanisms by which cocaine modulates adult hippocampal neurogenesis (AHN) and determine whether these adult-born neurons have a role in cocaine-related behaviors, such as cocaine-mediated cognitive symptoms. First, this review will summarize the cocaine-induced alterations in a number of neurobiological factors (neurotransmitters, neurotrophins, glucocorticoids, inflammatory mediators) that likely regulate both hippocampal-dependent learning and adult hippocampal neurogenesis after cocaine exposure. A separate section will provide a detailed review of the available literature that challenges the common view that cocaine reduces adult hippocampal neurogenesis. In fact, cocaine has a short-term anti-proliferative role, but the young adult-born neurons are apparently spared, or even enhanced, following certain cocaine protocols. Thus, we will try to reconcile this evidence with the hippocampal-dependent cognitive symptoms that are typically observed in cocaine addicts, and we will propose new directions for future studies to test the relevant hypothesis. Based on the evidence presented here, the regulation of adult hippocampal neurogenesis might be one of the many mechanisms by which cocaine sculpts hippocampus-dependent learning. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus.

Directory of Open Access Journals (Sweden)

Koshiro Inoue

Full Text Available Our six-week treadmill running training (forced exercise model has revealed that mild exercise (ME with an intensity below the lactate threshold (LT is sufficient to enhance spatial memory, while intense exercise (IE above the LT negates such benefits. To help understand the unrevealed neuronal and signaling/molecular mechanisms of the intensity-dependent cognitive change, in this rat model, we here investigated plasma corticosterone concentration as a marker of stress, adult hippocampal neurogenesis (AHN as a potential contributor to this ME-induced spatial memory, and comprehensively delineated the hippocampal transcriptomic profile using a whole-genome DNA microarray analysis approach through comparison with IE. Results showed that only IE had the higher corticosterone concentration than control, and that the less intense exercise (ME is better suited to improve AHN, especially in regards to the survival and maturation of newborn neurons. DNA microarray analysis using a 4 × 44 K Agilent chip revealed that ME regulated more genes than did IE (ME: 604 genes, IE: 415 genes, and only 41 genes were modified with both exercise intensities. The identified molecular components did not comprise well-known factors related to exercise-induced AHN, such as brain-derived neurotrophic factor. Rather, network analysis of the data using Ingenuity Pathway Analysis algorithms revealed that the ME-influenced genes were principally related to lipid metabolism, protein synthesis and inflammatory response, which are recognized as associated with AHN. In contrast, IE-influenced genes linked to excessive inflammatory immune response, which is a negative regulator of hippocampal neuroadaptation, were identified. Collectively, these results in a treadmill running model demonstrate that long-term ME, but not of IE, with minimizing running stress, has beneficial effects on increasing AHN, and provides an ME-specific gene inventory containing some potential regulators

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

Directory of Open Access Journals (Sweden)

Claudia G. Liberini

2016-10-01

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

Does developmental hypothyroidism produce lasting effects on adult neurogenesis?

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

Hongyu Pan

2016-10-01

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

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

Science.gov (United States)

BARNEA, ANAT; PRAVOSUDOV, VLADIMIR

2011-01-01

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

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

Science.gov (United States)

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

2014-09-01

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

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

NARCIS (Netherlands)

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

2015-01-01

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

Life-long stability of neurons: a century of research on neurogenesis, neuronal death and neuron quantification in adult CNS.

Science.gov (United States)

Turlejski, Kris; Djavadian, Ruzanna

2002-01-01

In this chapter we provide an extensive review of 100 years of research on the stability of neurons in the mammalian brain, with special emphasis on humans. Although Cajal formulated the Neuronal Doctrine, he was wrong in his beliefs that adult neurogenesis did not occur and adult neurons are dying throughout life. These two beliefs became accepted "common knowledge" and have shaped much of neuroscience research and provided much of the basis for clinical treatment of age-related brain diseases. In this review, we consider adult neurogenesis from a historical and evolutionary perspective. It is concluded, that while adult neurogenesis is a factor in the dynamics of the dentate gyrus and olfactory bulb, it is probably not a major factor during the life-span in most brain areas. Likewise, the acceptance of neuronal death as an explanation for normal age-related senility is challenged with evidence collected over the last fifty years. Much of the problem in changing this common belief of dying neurons was the inadequacies of neuronal counting methods. In this review we discuss in detail implications of recent improvements in neuronal quantification. We conclude: First, age-related neuronal atrophy is the major factor in functional deterioration of existing neurons and could be slowed down, or even reversed by various pharmacological interventions. Second, in most cases neuronal degeneration during aging is a pathology that in principle may be avoided. Third, loss of myelin and of the white matter is more frequent and important than the limited neuronal death in normal aging.

Inhibitory effects of caffeine on hippocampal neurogenesis and function.

Science.gov (United States)

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

2007-05-18

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

Understanding adult neurogenesis beyond its role in learning and memory formation

Directory of Open Access Journals (Sweden)

Ab Latif Wani

2017-04-01

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

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

Science.gov (United States)

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

Adult hippocampal neurogenesis and cognitive aging

Directory of Open Access Journals (Sweden)

Román Darío Moreno Fernández

2013-12-01

Full Text Available Aging is a normal developmental process associated with neurobiological changes leading to cognitive alterations with preserved, impaired, and enhanced functions. Evidence from animal and human studies is reviewed to explore the potential role of hippocampal plasticity on age-related cognitive changes with special attention to adult hippocampal neurogenesis. Results from lesion and stimulation strategies, as well as correlation data, support either a direct or modulatory role for adult newborn neurons in cognition at advanced ages. Further research on this topic may help to develop new treatments and to improve the quality of life of older people.

Effects of amphetamine administration on neurogenesis in adult rats

Directory of Open Access Journals (Sweden)

Tomasz Stępień

2017-12-01

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

The helix-loop-helix protein id1 controls stem cell proliferation during regenerative neurogenesis in the adult zebrafish telencephalon.

Science.gov (United States)

Rodriguez Viales, Rebecca; Diotel, Nicolas; Ferg, Marco; Armant, Olivier; Eich, Julia; Alunni, Alessandro; März, Martin; Bally-Cuif, Laure; Rastegar, Sepand; Strähle, Uwe

2015-03-01

The teleost brain has the remarkable ability to generate new neurons and to repair injuries during adult life stages. Maintaining life-long neurogenesis requires careful management of neural stem cell pools. In a genome-wide expression screen for transcription regulators, the id1 gene, encoding a negative regulator of E-proteins, was found to be upregulated in response to injury. id1 expression was mapped to quiescent type I neural stem cells in the adult telencephalic stem cell niche. Gain and loss of id1 function in vivo demonstrated that Id1 promotes stem cell quiescence. The increased id1 expression observed in neural stem cells in response to injury appeared independent of inflammatory signals, suggesting multiple antagonistic pathways in the regulation of reactive neurogenesis. Together, we propose that Id1 acts to maintain the neural stem cell pool by counteracting neurogenesis-promoting signals. © 2014 AlphaMed Press.

Wnt Signaling Is Required for Long-Term Memory Formation

Directory of Open Access Journals (Sweden)

Ying Tan

2013-09-01

Full Text Available Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous system, suggesting a potential role in behavioral processes. Here, we probed the requirement for Wnt signaling during olfactory memory formation in Drosophila using an inducible RNAi approach. Interfering with β-catenin expression in adult mushroom body neurons specifically impaired long-term memory (LTM without altering short-term memory. The impairment was reversible, being rescued by expression of a wild-type β-catenin transgene, and correlated with disruption of a cellular LTM trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt coreceptor, also impaired LTM. Wingless expression in wild-type flies was transiently elevated in the brain after LTM conditioning. Thus, inhibiting three key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM, indicating that this pathway mechanistically underlies this specific form of memory.

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

Science.gov (United States)

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

2012-12-01

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

HIPPOCAMPAL ADULT NEUROGENESIS: ITS REGULATION AND POTENTIAL ROLE IN SPATIAL LEARNING AND MEMORY

Science.gov (United States)

Lieberwirth, Claudia; Pan, Yongliang; Liu, Yan; Zhang, Zhibin; Wang, Zuoxin

2016-01-01

Adult neurogenesis, defined here as progenitor cell division generating functionally integrated neurons in the adult brain, occurs within the hippocampus of numerous mammalian species including humans. The present review details various endogenous (e.g., neurotransmitters) and environmental (e.g., physical exercise) factors that have been shown to influence hippocampal adult neurogenesis. In addition, the potential involvement of adult-generated neurons in naturally-occurring spatial learning behavior is discussed by summarizing the literature focusing on traditional animal models (e.g., rats and mice), non-traditional animal models (e.g., tree shrews), as well as natural populations (e.g., chickadees and Siberian chipmunk). PMID:27174001

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

Directory of Open Access Journals (Sweden)

Klaus Fabel

2009-11-01

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

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

Directory of Open Access Journals (Sweden)

Friederike Klempin

2010-07-01

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

Effects of curcumin on short-term spatial and recognition memory, adult neurogenesis and neuroinflammation in a streptozotocin-induced rat model of dementia of Alzheimer's type.

Science.gov (United States)

Bassani, Taysa B; Turnes, Joelle M; Moura, Eric L R; Bonato, Jéssica M; Cóppola-Segovia, Valentín; Zanata, Silvio M; Oliveira, Rúbia M M W; Vital, Maria A B F

2017-09-29

Curcumin is a natural polyphenol with evidence of antioxidant, anti-inflammatory and neuroprotective properties. Recent evidence also suggests that curcumin increases cognitive performance in animal models of dementia, and this effect would be related to its capacity to enhance adult neurogenesis. The aim of this study was to test the hypothesis that curcumin treatment would be able to preserve cognition by increasing neurogenesis and decreasing neuroinflammation in the model of dementia of Alzheimer's type induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) in Wistar rats. The animals were injected with ICV-STZ or vehicle and curcumin treatments (25, 50 and 100mg/kg, gavage) were performed for 30days. Four weeks after surgery, STZ-lesioned animals exhibited impairments in short-term spatial memory (Object Location Test (OLT) and Y maze) and short-term recognition memory (Object Recognition Test - ORT), decreased cell proliferation and immature neurons (Ki-67- and doublecortin-positive cells, respectively) in the subventricular zone (SVZ) and dentate gyrus (DG) of hippocampus, and increased immunoreactivity for the glial markers GFAP and Iba-1 (neuroinflammation). Curcumin treatment in the doses of 50 and 100mg/kg prevented the deficits in recognition memory in the ORT, but not in spatial memory in the OLT and Y maze. Curcumin treatment exerted only slight improvements in neuroinflammation, resulting in no improvements in hippocampal and subventricular neurogenesis. These results suggest a positive effect of curcumin in object recognition memory which was not related to hippocampal neurogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

Canales, Juan J

2013-01-01

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

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

Directory of Open Access Journals (Sweden)

Müller Anke

2010-06-01

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

The neurogenic factor NeuroD1 is expressed in post-mitotic cells during juvenile and adult Xenopus neurogenesis and not in progenitor or radial glial cells.

Directory of Open Access Journals (Sweden)

Laure Anne D'Amico

Full Text Available In contrast to mammals that have limited proliferation and neurogenesis capacities, the Xenopus frog exhibit a great potential regarding proliferation and production of new cells in the adult brain. This ability makes Xenopus a useful model for understanding the molecular programs required for adult neurogenesis. Transcriptional factors that control adult neurogenesis in vertebrate species undergoing widespread neurogenesis are unknown. NeuroD1 is a member of the family of proneural genes, which function during embryonic neurogenesis as a potent neuronal differentiation factor. Here, we study in detail the expression of NeuroD1 gene in the juvenile and adult Xenopus brains by in situ hybridization combined with immunodetections for proliferation markers (PCNA, BrdU or in situ hybridizations for cell type markers (Vimentin, Sox2. We found NeuroD1 gene activity in many brain regions, including olfactory bulbs, pallial regions of cerebral hemispheres, preoptic area, habenula, hypothalamus, cerebellum and medulla oblongata. We also demonstrated by double staining NeuroD1/BrdU experiments, after long post-BrdU administration survival times, that NeuroD1 gene activity was turned on in new born neurons during post-metamorphic neurogenesis. Importantly, we provided evidence that NeuroD1-expressing cells at this brain developmental stage were post-mitotic (PCNA- cells and not radial glial (Vimentin+ or progenitors (Sox2+ cells.

Sex steroids and neurogenesis.

Science.gov (United States)

Heberden, Christine

2017-10-01

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

Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain

Directory of Open Access Journals (Sweden)

Michalina Respondek

2015-12-01

Full Text Available Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC, which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

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

Directory of Open Access Journals (Sweden)

Fabio Cavaliere

2016-01-01

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

Neurogenesis and The Effect of Antidepressants

Directory of Open Access Journals (Sweden)

Philippe Taupin

2006-01-01

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

Neurogenesis and the Effect of Antidepressants

Directory of Open Access Journals (Sweden)

Philippe Taupin

2006-01-01

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

Enrichment increases hippocampal neurogenesis independent of blood monocyte-derived microglia presence following high-dose total body irradiation.

Science.gov (United States)

Ruitenberg, Marc J; Wells, Julia; Bartlett, Perry F; Harvey, Alan R; Vukovic, Jana

2017-06-01

Birth of new neurons in the hippocampus persists in the brain of adult mammals and critically underpins optimal learning and memory. The process of adult neurogenesis is significantly reduced following brain irradiation and this correlates with impaired cognitive function. In this study, we aimed to compare the long-term effects of two environmental paradigms (i.e. enriched environment and exercise) on adult neurogenesis following high-dose (10Gy) total body irradiation. When housed in standard (sedentary) conditions, irradiated mice revealed a long-lasting (up to 4 months) deficit in neurogenesis in the granule cell layer of the dentate gyrus, the region that harbors the neurogenic niche. This depressive effect of total body irradiation on adult neurogenesis was partially alleviated by exposure to enriched environment but not voluntary exercise, where mice were single-housed with unlimited access to a running wheel. Exposure to voluntary exercise, but not enriched environment, did lead to significant increases in microglia density in the granule cell layer of the hippocampus; our study shows that these changes result from local microglia proliferation rather than recruitment and infiltration of circulating Cx 3 cr1 +/gfp blood monocytes that subsequently differentiate into microglia-like cells. In summary, latent neural precursor cells remain present in the neurogenic niche of the adult hippocampus up to 8 weeks following high-dose total body irradiation. Environmental enrichment can partially restore the adult neurogenic process in this part of the brain following high-dose irradiation, and this was found to be independent of blood monocyte-derived microglia presence. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

Science.gov (United States)

Klomp, Anne; Václavů, Lena; Meerhoff, Gideon F; Reneman, Liesbeth; Lucassen, Paul J

2014-01-01

The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

Directory of Open Access Journals (Sweden)

Anne Klomp

Full Text Available The antidepressant drug fluoxetine (Prozac has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b effects on tryptophan hydroxylase (TPH expression, a measure of serotonin synthesis; c whether treatment effects during adolescence differed from treatment at an adult age, and d whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+ cells and of the number of young migratory neurons (doublecortin+, revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

Neurogenesis and Alzheimer's Disease

Directory of Open Access Journals (Sweden)

Philippe Taupin

2006-01-01

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

Neurogenesis and Alzheimer's Disease

Directory of Open Access Journals (Sweden)

Philippe Taupin

2006-01-01

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

Correlations between Hippocampal Neurogenesis and Metabolic Indices in Adult Nonhuman Primates

Directory of Open Access Journals (Sweden)

Tarique D. Perera

2011-01-01

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

Discovery of efficient stimulators for adult hippocampal neurogenesis based on scaffolds in dragon's blood.

Science.gov (United States)

Liang, Jian-Hua; Yang, Liang; Wu, Si; Liu, Si-Si; Cushman, Mark; Tian, Jing; Li, Nuo-Min; Yang, Qing-Hu; Zhang, He-Ao; Qiu, Yun-Jie; Xiang, Lin; Ma, Cong-Xuan; Li, Xue-Meng; Qing, Hong

2017-08-18

Reduction of hippocampal neurogenesis caused by aging and neurological disorders would impair neural circuits and result in memory loss. A new lead compound (N-trans-3',4'-methylenedioxystilben-4-yl acetamide 27) has been discovered to efficiently stimulate adult rats' neurogenesis. In-depth structure-activity relationship studies proved the necessity of a stilbene scaffold that is absent in highly cytotoxic analogs such as chalcones and heteroaryl rings and inactive analogs such as diphenyl acetylene and diphenyl ethane, and validated the importance of an NH in the carboxamide and a methylenedioxy substituent on the benzene ring. Immunohistochemical staining and biochemical analysis indicate, in contrast to previously reported neuroprotective chemicals, N-stilbenyl carboxamides have extra capacity for neuroproliferation-type neurogenesis, thereby providing a foundation for improving the plasticity of the adult mammalian brain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Imaizumi Yoichi

2011-01-01

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

Short-term and long-term effects of violent media on aggression in children and adults.

Science.gov (United States)

Bushman, Brad J; Huesmann, L Rowell

2006-04-01

To test whether the results of the accumulated studies on media violence and aggressive behavior are consistent with the theories that have evolved to explain the effects. We tested for the existence of both short-term and long-term effects for aggressive behavior. We also tested the theory-driven hypothesis that short-term effects should be greater for adults and long-term effects should be greater for children. Meta-analysis. Children younger than 18 years and adults. Violent media, including TV, movies, video games, music, and comic books. Measures of aggressive behavior, aggressive thoughts, angry feelings, physiological arousal (eg, heart rate, blood pressure), and helping behavior. Effect size estimates were combined using meta-analytic procedures. As expected, the short-term effects of violent media were greater for adults than for children whereas the long-term effects were greater for children than for adults. The results also showed that there were overall modest but significant effect sizes for exposure to media violence on aggressive behaviors, aggressive thoughts, angry feelings, arousal levels, and helping behavior. The results are consistent with the theory that short-term effects are mostly due to the priming of existing well-encoded scripts, schemas, or beliefs, which adults have had more time to encode. In contrast, long-term effects require the learning (encoding) of scripts, schemas, or beliefs. Children can encode new scripts, schemas, and beliefs via observational learning with less interference and effort than adults.

Assessing the associative deficit of older adults in long-term and short-term/working memory.

Science.gov (United States)

Chen, Tina; Naveh-Benjamin, Moshe

2012-09-01

Older adults exhibit a deficit in associative long-term memory relative to younger adults. However, the literature is inconclusive regarding whether this deficit is attenuated in short-term/working memory. To elucidate the issue, three experiments assessed younger and older adults' item and interitem associative memory and the effects of several variables that might potentially contribute to the inconsistent pattern of results in previous studies. In Experiment 1, participants were tested on item and associative recognition memory with both long-term and short-term retention intervals in a single, continuous recognition paradigm. There was an associative deficit for older adults in the short-term and long-term intervals. Using only short-term intervals, Experiment 2 utilized mixed and blocked test designs to examine the effect of test event salience. Blocking the test did not attenuate the age-related associative deficit seen in the mixed test blocks. Finally, an age-related associative deficit was found in Experiment 3, under both sequential and simultaneous presentation conditions. Even while accounting for some methodological issues, the associative deficit of older adults is evident in short-term/working memory.

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

Science.gov (United States)

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

2013-04-01

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

Age-dependent role for Ras-GRF1 in the late stages of adult neurogenesis in the dentate gyrus.

Science.gov (United States)

Darcy, Michael J; Trouche, Stéphanie; Jin, Shan-Xue; Feig, Larry A

2014-03-01

The dentate gyrus of the hippocampus plays a pivotal role in pattern separation, a process required for the behavioral task of contextual discrimination. One unique feature of the dentate gyrus that contributes to pattern separation is adult neurogenesis, where newly born neurons play a distinct role in neuronal circuitry. Moreover,the function of neurogenesis in this brain region differs in adolescent and adult mice. The signaling mechanisms that differentially regulate the distinct steps of adult neurogenesis in adolescence and adulthood remain poorly understood. We used mice lacking RASGRF1(GRF1), a calcium-dependent exchange factor that regulates synaptic plasticity and participates in contextual discrimination performed by mice, to test whether GRF1 plays a role in adult neurogenesis.We show Grf1 knockout mice begin to display a defect in neurogenesis at the onset of adulthood (~2 months of age), when wild-type mice first acquire the ability to distinguish between closely related contexts. At this age, young hippocampal neurons in Grf1 knockout mice display severely reduced dendritic arborization. By 3 months of age, new neuron survival is also impaired. BrdU labeling of new neurons in 2-month-old Grf1 knockout mice shows they begin to display reduced survival between 2 and 3 weeks after birth, just as new neurons begin to develop complex dendritic morphology and transition into using glutamatergic excitatory input. Interestingly, GRF1 expression appears in new neurons at the developmental stage when GRF1 loss begins to effect neuronal function. In addition, we induced a similar loss of new hippocampal neurons by knocking down expression of GRF1 solely in new neurons by injecting retrovirus that express shRNA against GRF1 into the dentate gyrus. Together, these findings show that GRF1 expressed in new neurons promotes late stages of adult neurogenesis. Overall our findings show GRF1 to be an age-dependent regulator of adult hippocampal neurogenesis, which

The Long Run: Neuroprotective Effects of Physical Exercise on Adult Neurogenesis from Youth to Old Age

Science.gov (United States)

Saraulli, Daniele; Costanzi, Marco; Mastrorilli, Valentina; Farioli-Vecchioli, Stefano

2017-01-01

Background The rapid lengthening of life expectancy has raised the problem of providing social programs to counteract the age-related cognitive decline in a growing number of older people. Physical activity stands among the most promising interventions aimed at brain wellbeing, because of its effective neuroprotective action and low social cost. The purpose of this review is to describe the neuroprotective role exerted by physical activity in different life stages. In particular, we focus on adult neurogenesis, a process which has proved being highly responsive to physical exercise and may represent a major factor of brain health over the lifespan. Methods The most recent literature related to the subject has been reviewed. The text has been divided into three main sections, addressing the effects of physical exercise during childhood/adolescence, adulthood and aging, respectively. For each one, the most relevant studies, carried out on both human participants and rodent models, have been described. Results The data reviewed converge in indicating that physical activity exerts a positive effect on brain functioning throughout the lifespan. However, uncertainty remains about the magnitude of the effect and its biological underpinnings. Cellular and synaptic plasticity provided by adult neurogenesis are highly probable mediators, but the mechanism for their action has yet to be conclusively established. Conclusion Despite alternative mechanisms of action are currently debated, age-appropriate physical activity programs may constitute a large-scale, relatively inexpensive and powerful approach to dampen the individual and social impact of age-related cognitive decline. PMID:27000776

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

Science.gov (United States)

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

2017-05-01

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

Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

Science.gov (United States)

Bond, Allison M.; Ming, Guo-li; Song, Hongjun

2015-01-01

Summary Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. PMID:26431181

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

OpenAIRE

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

2013-01-01

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

In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis.

Science.gov (United States)

Lim, Daniel A; Suárez-Fariñas, Mayte; Naef, Felix; Hacker, Coleen R; Menn, Benedicte; Takebayashi, Hirohide; Magnasco, Marcelo; Patil, Nila; Alvarez-Buylla, Arturo

2006-01-01

Neural stem cells and neurogenesis persist in the adult mammalian brain subventricular zone (SVZ). Cells born in the rodent SVZ migrate to the olfactory bulb (Ob) where they differentiate into interneurons. To determine the gene expression and functional profile of SVZ neurogenesis, we performed three complementary sets of transcriptional analysis experiments using Affymetrix GeneChips: (1) comparison of adult mouse SVZ and Ob gene expression profiles with those of the striatum, cerebral cortex, and hippocampus; (2) profiling of SVZ stem cells and ependyma isolated by fluorescent-activated cell sorting (FACS); and (3) analysis of gene expression changes during in vivo SVZ regeneration after anti-mitotic treatment. Gene Ontology (GO) analysis of data from these three separate approaches showed that in adult SVZ neurogenesis, RNA splicing and chromatin remodeling are biological processes as statistically significant as cell proliferation, transcription, and neurogenesis. In non-neurogenic brain regions, RNA splicing and chromatin remodeling were not prominent processes. Fourteen mRNA splicing factors including Sf3b1, Sfrs2, Lsm4, and Khdrbs1/Sam68 were detected along with 9 chromatin remodeling genes including Mll, Bmi1, Smarcad1, Baf53a, and Hat1. We validated the transcriptional profile data with Northern blot analysis and in situ hybridization. The data greatly expand the catalogue of cell cycle components, transcription factors, and migration genes for adult SVZ neurogenesis and reveal RNA splicing and chromatin remodeling as prominent biological processes for these germinal cells.

Is forebrain neurogenesis a potential repair mechanism after stroke?

OpenAIRE

Inta, Dragos; Gass, Peter

2015-01-01

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

Adult neurogenesis affects motivation to obtain weak, but not strong, reward in operant tasks.

Science.gov (United States)

Karlsson, Rose-Marie; Wang, Alice S; Sonti, Anup N; Cameron, Heather A

2018-04-16

Decreased motivation to seek rewards is a key feature of mood disorders that correlates with severity and treatment outcome. This anhedonia, or apathy, likely reflects impairment in reward circuitry, but the specific neuronal populations controlling motivation are unclear. Granule neurons generated in the adult hippocampus have been implicated in mood disorders, but are not generally considered as part of reward circuits. We investigated a possible role of these new neurons in motivation to work for food and sucrose rewards in operant conditioning tasks using GFAP-TK pharmacogenetic ablation of adult neurogenesis in both rats and mice. Rats and mice lacking adult neurogenesis showed normal lever press responding during fixed ratio training, reward devaluation, and Pavlovian Instrumental Transfer, suggesting no impairment in learning. However, on an exponentially progressive ratio schedule, or when regular chow was freely available in the testing chamber, TK rats and mice showed less effort to gain sucrose tablets. When working for balanced food tablets, which rats and mice of both genotypes strongly preferred over sucrose, the genotype effects on behavior were lost. This decrease in effort under conditions of low reward suggests that loss of adult neurogenesis decreases motivation to seek reward in a manner that may model behavioral apathy. © 2018 Wiley Periodicals, Inc.

Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

Directory of Open Access Journals (Sweden)

Kuan Zhang

Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

Science.gov (United States)

Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

2016-02-01

Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adult Hippocampal Neurogenesis in Parkinson’s Disease: Impact on Neuronal Survival and Plasticity

Directory of Open Access Journals (Sweden)

Martin Regensburger

2014-01-01

Full Text Available In Parkinson’s disease (PD and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research.

Untangling the influences of voluntary running, environmental complexity, social housing and stress on adult hippocampal neurogenesis.

Directory of Open Access Journals (Sweden)

Catherine-Alexandra Grégoire

Full Text Available Environmental enrichment (EE exerts powerful effects on brain physiology, and is widely used as an experimental and therapeutic tool. Typical EE paradigms are multifactorial, incorporating elements of physical exercise, environmental complexity, social interactions and stress, however the specific contributions of these variables have not been separable using conventional housing paradigms. Here, we evaluated the impacts of these individual variables on adult hippocampal neurogenesis by using a novel "Alternating EE" paradigm. For 4 weeks, adult male CD1 mice were alternated daily between two enriched environments; by comparing groups that differed in one of their two environments, the individual and combinatorial effects of EE variables could be resolved. The Alternating EE paradigm revealed that (1 voluntary running for 3 days/week was sufficient to increase both mitotic and post-mitotic stages of hippocampal neurogenesis, confirming the central importance of exercise; (2 a complex environment (comprised of both social interactions and rotated inanimate objects had no effect on neurogenesis itself, but enhanced depolarization-induced c-Fos expression (attributable to social interactions and buffered stress-induced plasma corticosterone levels (attributable to inanimate objects; and (3 neither social isolation, group housing, nor chronically increased levels of plasma corticosterone had a prolonged impact on neurogenesis. Mouse strain, handling and type of running apparatus were tested and excluded as potential confounding factors. These findings provide valuable insights into the relative effects of key EE variables on adult neurogenesis, and this "Alternating EE" paradigm represents a useful tool for exploring the contributions of individual EE variables to mechanisms of neural plasticity.

Untangling the Influences of Voluntary Running, Environmental Complexity, Social Housing and Stress on Adult Hippocampal Neurogenesis

Science.gov (United States)

Grégoire, Catherine-Alexandra; Bonenfant, David; Le Nguyen, Adalie; Aumont, Anne; Fernandes, Karl J. L.

2014-01-01

Environmental enrichment (EE) exerts powerful effects on brain physiology, and is widely used as an experimental and therapeutic tool. Typical EE paradigms are multifactorial, incorporating elements of physical exercise, environmental complexity, social interactions and stress, however the specific contributions of these variables have not been separable using conventional housing paradigms. Here, we evaluated the impacts of these individual variables on adult hippocampal neurogenesis by using a novel “Alternating EE” paradigm. For 4 weeks, adult male CD1 mice were alternated daily between two enriched environments; by comparing groups that differed in one of their two environments, the individual and combinatorial effects of EE variables could be resolved. The Alternating EE paradigm revealed that (1) voluntary running for 3 days/week was sufficient to increase both mitotic and post-mitotic stages of hippocampal neurogenesis, confirming the central importance of exercise; (2) a complex environment (comprised of both social interactions and rotated inanimate objects) had no effect on neurogenesis itself, but enhanced depolarization-induced c-Fos expression (attributable to social interactions) and buffered stress-induced plasma corticosterone levels (attributable to inanimate objects); and (3) neither social isolation, group housing, nor chronically increased levels of plasma corticosterone had a prolonged impact on neurogenesis. Mouse strain, handling and type of running apparatus were tested and excluded as potential confounding factors. These findings provide valuable insights into the relative effects of key EE variables on adult neurogenesis, and this “Alternating EE” paradigm represents a useful tool for exploring the contributions of individual EE variables to mechanisms of neural plasticity. PMID:24465980

Influence of superior cervical ganglionectomy on hippocampal neurogenesis and learning and memory in adult rats

Institute of Scientific and Technical Information of China (English)

Yanping Ding; Baoping Shao; Shiyuan Yu; Shanting Zhao; Jianlin Wang

2009-01-01

BACKGROUND: Studies have shown that neurogenesis in the dentate gyrus plays an important role in learning and memory. However, studies have not determined whether the superior cervical ganglion or the sympathetic nerve system influences hippocampal neurogenesis or learning and memory in adult rats. OBJECTIVE: To observe differences in dentate gyrus neurogenesis, as well as learning and memory, in adult rats following superior cervical ganglionectomy. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Immunohistochemistry Laboratory of the School of Life Sciences in Lanzhou University from July 2006 to July 2007.MATERIALS: Doublecortin polyclonal antibody was provided by Santa Cruz Biotechnology, USA;avidin-biotin-peroxidase complex was purchased from Zhongshan Goldenbride Biotechnology, China;Morris water maze was bought from Taimeng Technology, China. METHODS: A total of 20 adult, male, Wistar rats were randomly divided into surgery and control groups, with 10 rats in each group. In the surgery group, the bilateral superior cervical ganglions were transected. In the control group, the superior cervical ganglions were only exposed, but no ganglionectomy was performed. MAIN OUTCOME MEASURES: To examine distribution, morphology, and number of newborn neurons in the dentate gyrus using doublecortin immunohistochemistry at 36 days following surgical procedures. To examine ability of learning and memory in adult rats using the Morris water maze at 30 days following surgical procedures. RESULTS: Doublecortin immunohistochemical results showed that a reduction in the number of doublecortin-positive neurons in the surgery group compared to the control group (P＜0.05), while the distribution of doublecortin-positive neurons was identical in the two groups. The surgery group exhibited significantly worse performance in learning and spatial memory tasks compared to the control group (P＜0.05). CONCLUSION: Superior cervical ganglionectomy

Delayed and transient increase of adult hippocampal neurogenesis by physical exercise in DBA/2 mice.

Directory of Open Access Journals (Sweden)

Rupert W Overall

Full Text Available This study builds on the findings that physical activity, such as wheel running in mice, enhances cell proliferation and neurogenesis in the adult hippocampus of the common mouse strain C57BL/6, and that the baseline level of neurogenesis varies by strain, being considerably lower in DBA/2. Because C57BL/6 and DBA/2 are important as the parental strains of the BXD recombinant inbred cross which allows the detection of genetic loci regulating phenotypes such as adult neurogenesis, we performed the current study to investigate the gene x environment interactions regulating neurogenesis. At equal distances and times run DBA/2J mice lacked the acute increase in precursor cell proliferation known from C57BL/6. In DBA/2J proliferation even negatively correlated with the distance run. This was neither due to a stress response (to running itself or single housing nor differences in estrous cycle. DBA/2 animals exhibited a delayed and weaker pro-neurogenic response with a significant increase in numbers of proliferating cells first detectable after more than a week of wheel running. The proliferative response to running was transient in both strains, the effect being undetectable by 6 weeks. There was also a small transient increase in the production of new neurons in DBA/2J, although these extra cells did not survive. These findings indicate that the comparison between C57BL/6 and DBA/2, and by extension the BXD genetic reference population derived from these strains, should provide a powerful tool for uncovering the complex network of modifier genes affecting the activity-dependent regulation of adult hippocampal neurogenesis. More generally, our findings also describe how the external physical environment interacts with the internal genetic environment to produce different responses to the same behavioral stimuli.

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

Directory of Open Access Journals (Sweden)

Moritz D. Brandt

2017-08-01

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

Long-Term Prognosis of Ischemic Stroke in Young Adults

OpenAIRE

Varona, Jose F.

2010-01-01

There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The prese...

Barriers to ethical nursing practice for older adults in long-term care facilities.

Science.gov (United States)

Choe, Kwisoon; Kang, Hyunwook; Lee, Aekyung

2018-03-01

To explore barriers to ethical nursing practice for older adults in long-term care facilities from the perspectives of nurses in South Korea. The number of older adults admitted to long-term care facilities is increasing rapidly in South Korea. To provide this population with quality care, a solid moral foundation should be emphasised to ensure the provision of ethical nursing practices. Barriers to implementing an ethical nursing practice for older adults in long-term care facilities have not been fully explored in previous literature. A qualitative, descriptive design was used to explore barriers to ethical nursing practice as perceived by registered nurses in long-term care facilities in South Korea. Individual interviews were conducted with 17 registered nurses recruited using purposive (snowball) sampling who care for older adults in long-term care facilities in South Korea. Data were analysed using qualitative content analysis. Five main themes emerged from the data analysis concerning barriers to the ethical nursing practice of long-term care facilities: emotional distress, treatments restricting freedom of physical activities, difficulty coping with emergencies, difficulty communicating with the older adult patients and friction between nurses and nursing assistants. This study has identified methods that could be used to improve ethical nursing practices for older adults in long-term care facilities. Because it is difficult to improve the quality of care through education and staffing alone, other factors may also require attention. Support programmes and educational opportunities are needed for nurses who experience emotional distress and lack of competency to strengthen their resilience towards some of the negative aspects of care and being a nurse that were identified in this study. © 2017 John Wiley & Sons Ltd.

Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis

Science.gov (United States)

Opendak, Maya; Offit, Lily; Monari, Patrick; Schoenfeld, Timothy J.; Sonti, Anup N.; Cameron, Heather A.

2016-01-01

Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Social disruption produced a preference for familiar over novel conspecifics, a change that did not involve global memory impairments or increased anxiety. Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels. Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP–thymidine kinase rats resulted in social behavior similar to disrupted rats. Together, these results provide novel mechanistic evidence that social disruption shapes behavior in a potentially adaptive way, possibly by reducing adult neurogenesis in the hippocampus. SIGNIFICANCE STATEMENT To investigate cellular processes underlying adaptation to social instability, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Unexpectedly, these changes were accompanied by changes in social strategies without evidence of impairments in cognition or anxiety regulation. Restoring adult neurogenesis in disrupted rats using oxytocin and conditionally suppressing the production of new neurons in socially naive GFAP–thymidine kinase rats showed that loss of 6-week-old neurons may be responsible for adaptive changes in social behavior. PMID:27358459

Long-term psychological functioning of adults with severe congenital facial disfigurement

NARCIS (Netherlands)

Passchier, J.; Versnel, S.L.; Plomp, R.G.; Duivenvoorden, H.J.; Mathijssen, I.M.

2012-01-01

BACKGROUND: In adults with severe congenital facial disfigurement, assessment of long-term psychological impact remains limited. This study determines the long-term psychological functioning in these patients and evaluates differences compared with patients with acquired facial disfigurement and a

Taurine increases hippocampal neurogenesis in aging mice

Directory of Open Access Journals (Sweden)

Elias Gebara

2015-05-01

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

Decreasing Trend in the Use and Long-Term Use of Benzodiazepines Among Young Adults.

Science.gov (United States)

Tähkäpää, Sanna-Mari; Saastamoinen, Leena; Airaksinen, Marja; Tuulio-Henriksson, Annamari; Aalto-Setälä, Terhi; Kurko, Terhi

2018-03-14

Patterns of benzodiazepine (BZD) use and long-term use among young adults are not well known. Our aim was to study trends in BZD use and long-term use among 18-25-year-old young adults by gender and active substance in a nationwide retrospective longitudinal register-based setting. All Finns aged 18-25 years with reimbursed purchases of BZDs in 2006-2014 recorded to the Finnish Prescription Register were included. Annual prevalence rates of BZD use and long-term use among young adults were reported overall, according to gender, drug group (anxiolytic or hypnotic), and active substance. Long-term use of BZDs was defined as purchasing ≥180 Defined Daily Doses (DDDs) in at least two drug purchases during a calendar year. Overall prevalence of BZD use among young adults decreased from 24.0 to 18.8 users per 1000 inhabitants in 2006-2014. Prevalence of long-term use decreased from 5.5 to 3.3 users per 1000 inhabitants. Overall BZD use was higher among females, whereas long-term use was more common among males. Use of anxiolytics was more common than use of hypnotics. Oxazepam, alprazolam, zopiclone, and zolpidem were the most used BZDs, whereas alprazolam and clonazepam were the substances with most long-term use. The use and long-term use of BZDs have decreased annually since 2008 among Finnish young adults. Further research is needed to investigate the reasons behind the decline.

Long term exposure to combination paradigm of environmental enrichment, physical exercise and diet reverses the spatial memory deficits and restores hippocampal neurogenesis in ventral subicular lesioned rats.

Science.gov (United States)

Kapgal, Vijayakumar; Prem, Neethi; Hegde, Preethi; Laxmi, T R; Kutty, Bindu M

2016-04-01

Subiculum is an important structure of the hippocampal formation and plays an imperative role in spatial learning and memory functions. We have demonstrated earlier the cognitive impairment following bilateral ventral subicular lesion (VSL) in rats. We found that short term exposure to enriched environment (EE) did not help to reverse the spatial memory deficits in water maze task suggesting the need for an appropriate enriched paradigm towards the recovery of spatial memory. In the present study, the efficacy of long term exposure of VSL rats to combination paradigm of environmental enrichment (EE), physical exercise and 18 C.W. diet (Combination Therapy - CT) in reversing the spatial memory deficits in Morris water maze task has been studied. Ibotenate lesioning of ventral subiculum produced significant impairment of performance in the Morris water maze and reduced the hippocampal neurogenesis in rats. Post lesion exposure to C.T. restored the hippocampal neurogenesis and improved the spatial memory functions in VSL rats. Our study supports the hypothesis that the combination paradigm is critical towards the development of an enhanced behavioral and cognitive experience especially in conditions of CNS insults and the associated cognitive dysfunctions. Copyright © 2016 Elsevier Inc. All rights reserved.

Delayed behavioral dysfunctions following exposure to ionising radiation: role of neurogenesis

International Nuclear Information System (INIS)

Haridas, Seenu; Kumar, Mayank; Manda, Kailash

2014-01-01

Being a terminally differentiated organ, the brain has been considered to be a radioresistant one. Traditionally, delayed radiation-induced CNS damage was hypothesized as chiefly attributable to impaired vascular endothelial system and neuroinflammatory glial cell populations. In the recent decades, preclinical studies have focused on the hippocampal dentate gyrus, one of two discrete sites of the brain where adult neurogenesis takes place. Neurogenesis, in such area of the brain takes place throughout the adulthood and makes the brain highly vulnerable to the radiation. Recent investigations, including our own reports indicated that radiation ablates hippocampal neurogenesis, alters neuronal function, and induces neuroinflammation. Since the hippocampus is involved in learning and memory, behavioral adaptation and HPA axis regulation, damage by radiation leads to severe behavioral and cognitive dysfunctions. The present study aimed at evaluating the delayed effects of gamma-irradiation on the cognitive and affective functions, which were further corroborated to changes in neurogenesis. C57BL/6J mice were exposed to whole body irradiation as well as cranial irradiation by gamma-rays at different sub-lethal doses. The behavioral tests, consisting spontaneous motor activity, open field test, novel object recognition test, forced swim test and Morris water maze were performed at 1 month and 5 months post-exposure. Neurogenic potential was evaluated using flow-cytometry (FC) and immuno-histo-chemistry (IHC). The results indicated the significant changes in the affective and cognitive functions at delayed time points of radiation exposure. Profound alteration in the anxiety and depressive phenotype was observed following irradiation. Additionally, both long term and short term memory functions were disrupted, which were attributable to changes in the neurogenic potential as reported in the terms of BrdU positive cells using FC and IHC. Present investigation clearly

Inhibition of Adult Neurogenesis through ERK5 knockdown Impairs Complex Hippocampus-dependent Spatial Memory Tasks

NARCIS (Netherlands)

Fitzsimons, C.P.; Vreugdenhil, E.; Lucassen, P.J.

2012-01-01

This study reports on the identification of the extracellular MAPK ERK5 as a novel signaling molecule regulating adult hippocampal neurogenesis. The authors use an inducible and conditional mouse line to knockout ERK5 expression, specifically in the neurogenic regions of the adult brain and provide

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

Science.gov (United States)

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

2017-12-04

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

Selective alteration of adult hippocampal neurogenesis and impaired spatial pattern separation performance in the RSK2-deficient mouse model of Coffin-Lowry syndrome.

Science.gov (United States)

Castillon, Charlotte; Lunion, Steeve; Desvignes, Nathalie; Hanauer, André; Laroche, Serge; Poirier, Roseline

2018-07-01

Adult neurogenesis is involved in certain hippocampus-dependent cognitive functions and is linked to psychiatric diseases including intellectual disabilities. The Coffin-Lowry syndrome (CLS) is a developmental disorder caused by mutations in the Rsk2 gene and characterized by intellectual disabilities associated with growth retardation. How RSK2-deficiency leads to cognitive dysfunctions in CLS is however poorly understood. Here, using Rsk2 Knock-Out mice, we characterized the impact of RSK2 deficiency on adult hippocampal neurogenesis in vivo. We report that the absence of RSK2 does not affect basal proliferation, differentiation and survival of dentate gyrus adult-born neurons but alters the maturation progression of young immature newborn neurons. Moreover, when RSK2-deficient mice were submitted to spatial learning, in contrast to wild-type mice, proliferation of adult generated neurons was decreased and no pro-survival effect of learning was observed. Thus, learning failed to recruit a selective population of young newborn neurons in association with deficient long-term memory recall. Given the proposed role of the dentate gyrus and of adult-generated newborn neurons in hippocampal-dependent pattern separation function, we explored this function in a delayed non-matching to place task and in an object-place pattern separation task and report severe deficits in spatial pattern separation in Rsk2-KO mice. Together, this study reveals a previously unknown role for RSK2 in the early stages of maturation and learning-dependent involvement of adult-born dentate gyrus neurons. These alterations associated with a deficit in the ability of RSK2-deficient mice to finely discriminate relatively similar spatial configurations, may contribute to cognitive dysfunction in CLS. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2016-05-01

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

An old test for new neurons: refining the Morris water maze to study the functional relevance of adult hippocampal neurogenesis

Directory of Open Access Journals (Sweden)

Alexander eGarthe

2013-05-01

Full Text Available The Morris water maze represents the de-facto standard for testing hippocampal function in laboratory rodents. In the field of adult hippocampal neurogenesis, however, using this paradigm to assess the functional relevance of the new neurons yielded surprisingly inconsistent results. While some authors found aspects of water maze performance to be linked to adult neurogenesis, others obtained different results or could not demonstrate any effect of manipulating adult neurogenesis.In this review we discuss evidence that the large diversity of protocols and setups used is an important aspect in interpreting the differences in the results that have been obtained. Even simple parameters such as pool size, number and configuration of visual landmarks, or number of trials can become highly relevant for getting the new neurons involved at all. Sets of parameters are often chosen with implicit or explicit concepts in mind and these might lead to different views on the function of adult-generated neurons.We propose that the classical parameters usually used to measure spatial learning performance in the water maze might not be particularly well suited to sensitively and specifically detect the supposedly highly specific functional changes elicited by the experimental modulation of adult hippocampal neurogenesis. As adult neurogenesis is supposed to affect specific aspects of information processing only in the hippocampus, any claim for a functional relevance of the new neurons has to be based on hippocampus-specific parameters. We also placed a special emphasis on the fact that the DG facilitates the differentiation between contexts as opposed to just differentiating places.In conclusion, while the Morris water maze has proven to be one of the most effective testing paradigms to assess hippocampus-dependent spatial learning, new and more specific questions ask for new parameters. Therefore, the full potential of the water maze task remains to be tapped.

The long-term effectiveness of generic adult fixed-dose combination ...

African Journals Online (AJOL)

Background: Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs. Objective: To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment. Methods: ...

Opposing Effects of α2- and β-Adrenergic Receptor Stimulation on Quiescent Neural Precursor Cell Activity and Adult Hippocampal Neurogenesis

Science.gov (United States)

Prosper, Boris W.; Marathe, Swanand; Husain, Basma F. A.; Kernie, Steven G.; Bartlett, Perry F.; Vaidya, Vidita A.

2014-01-01

Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and β-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of β-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and β-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis. PMID:24922313

Reparative neurogenesis after cerebral ischemia: Clinical application prospects

Energy Technology Data Exchange (ETDEWEB)

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

2015-11-17

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

Reparative neurogenesis after cerebral ischemia: Clinical application prospects

Science.gov (United States)

Khodanovich, M. Yu.

2015-11-01

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

Reparative neurogenesis after cerebral ischemia: Clinical application prospects

International Nuclear Information System (INIS)

Khodanovich, M. Yu.

2015-01-01

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

Circadian Clock Genes Are Essential for Normal Adult Neurogenesis, Differentiation, and Fate Determination.

Directory of Open Access Journals (Sweden)

Astha Malik

Full Text Available Adult neurogenesis creates new neurons and glia from stem cells in the human brain throughout life. It is best understood in the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ. Circadian rhythms have been identified in the hippocampus, but the role of any endogenous circadian oscillator cells in hippocampal neurogenesis and their importance in learning or memory remains unclear. Any study of stem cell regulation by intrinsic circadian timing within the DG is complicated by modulation from circadian clocks elsewhere in the brain. To examine circadian oscillators in greater isolation, neurosphere cultures were prepared from the DG of two knockout mouse lines that lack a functional circadian clock and from mPer1::luc mice to identify circadian oscillations in gene expression. Circadian mPer1 gene activity rhythms were recorded in neurospheres maintained in a culture medium that induces neurogenesis but not in one that maintains the stem cell state. Although the differentiating neural stem progenitor cells of spheres were rhythmic, evidence of any mature neurons was extremely sparse. The circadian timing signal originated in undifferentiated cells within the neurosphere. This conclusion was supported by immunocytochemistry for mPER1 protein that was localized to the inner, more stem cell-like neurosphere core. To test for effects of the circadian clock on neurogenesis, media conditions were altered to induce neurospheres from BMAL1 knockout mice to differentiate. These cultures displayed unusually high differentiation into glia rather than neurons according to GFAP and NeuN expression, respectively, and very few BetaIII tubulin-positive, immature neurons were observed. The knockout neurospheres also displayed areas visibly devoid of cells and had overall higher cell death. Neurospheres from arrhythmic mice lacking two other core clock genes, Cry1 and Cry2, showed significantly reduced growth and increased astrocyte

Long-Term Cognitive Impairment After First-Ever Ischemic Stroke in Young Adults

NARCIS (Netherlands)

Schaapsmeerders, P.; Maaijwee, N.A.M.M.; Dijk, E.J. van; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Kessels, R.P.C.; Leeuw, H.F. de

2013-01-01

Background and Purpose—Up to 14% of all ischemic strokes occur in young adults (<50 years). Poststroke cognitive performance is a decisive determinant of their quality of life. However, virtually no studies report on cognition after young stroke, especially not on the long term. This long-term

Long-term cognitive impairment after first-ever ischemic stroke in young adults

NARCIS (Netherlands)

Schaapsmeerders, P.; Maaijwee, N.A.M.M.; Dijk, E.J. van; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Kessels, R.P.C.; Leeuw, F.E. de

2013-01-01

BACKGROUND AND PURPOSE: Up to 14% of all ischemic strokes occur in young adults (<50 years). Poststroke cognitive performance is a decisive determinant of their quality of life. However, virtually no studies report on cognition after young stroke, especially not on the long term. This long-term

Long-term psychological functioning of adults with severe congenital facial disfigurement.

Science.gov (United States)

Versnel, Sarah L; Plomp, Raul G; Passchier, Jan; Duivenvoorden, Hugo J; Mathijssen, Irene M J

2012-01-01

In adults with severe congenital facial disfigurement, assessment of long-term psychological impact remains limited. This study determines the long-term psychological functioning in these patients and evaluates differences compared with patients with acquired facial disfigurement and a non-facially disfigured reference group. Also explored is the extent to which psychological functioning of the congenital group is related to satisfaction with facial appearance, fear of negative appearance evaluation by others, self-esteem, and severity of the facial deformity. Fifty-nine adults with severe congenital facial disfigurement, 59 adults with a traumatically acquired facial deformity in adulthood, and 120 non-facially disfigured adults completed standardized psychological, physical, and demographic questionnaires, including the Fear of Negative Appearance Evaluation Scale, the Rosenberg Self-Esteem Scale, the Hospital Anxiety and Depression Scale, the Achenbach Adult Self-Report, the 36-Item Short-Form Health Survey, and a visual analogue scale. Adults with severe congenital facial disfigurement had relatively normal psychological functioning but appeared more prone to internalizing problems than the non-facially disfigured adults. Compared with patients with an acquired facial deformity, the congenital group displayed fewer problems on the physical component score of quality of life only. Satisfaction with facial appearance, fear of negative appearance evaluation, and self-esteem were good predictors of the different aspects of psychological functioning, with the exception of the physical component score of quality of life. Improving satisfaction with facial appearance (by surgery), enhancing self-esteem, or lowering fear of negative appearance evaluation (by psychological support) may enhance long-term psychological functioning. Future research should focus on the individual patient and risk factors for maladjustment. Risk, II.

Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

Directory of Open Access Journals (Sweden)

Eleni Paizanis

2007-01-01

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

Long-term mortality after stroke among adults aged 18 to 50 years

NARCIS (Netherlands)

Rutten-Jacobs, L.C.A.; Arntz, R.M.; Maaijwee, N.A.M.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Dijk, E.J. van; Leeuw, F.E. de

2013-01-01

IMPORTANCE: Long-term data on mortality after first-ever stroke in adults aged 18 through 50 years are scarce and usually restricted to ischemic stroke. Moreover, expected mortality not related to first-ever stroke is not taken in account. OBJECTIVES To investigate long-term mortality and cause of

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

Directory of Open Access Journals (Sweden)

Valentina Tosetti

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

Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action

NARCIS (Netherlands)

Lucassen, P.J.; Meerlo, P.; Naylor, A.S.; van Dam, A.M.; Dayer, A.G.; Fuchs, E.; Oomen, C.A.; Czéh, B.

2010-01-01

Adult hippocampal neurogenesis, a once unorthodox concept, has changed into one of the most rapidly growing fields in neuroscience. The present report results from the ECNP targeted expert meeting in 2007 during which cellular plasticity changes were addressed in the adult brain, focusing on

Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation : Implications for depression and antidepressant action

NARCIS (Netherlands)

Lucassen, P. J.; Meerlo, P.; Naylor, A. S.; van Dam, A.M.; Dayer, A. G.; Fuchs, E.; Oomen, C. A.; Czeh, B.

2010-01-01

Adult hippocampal. neurogenesis, a once unorthodox concept, has changed into one of the most rapidly growing fields in neuroscience. The present report results from the ECNP targeted expert meeting in 2007 during which cellular plasticity changes were addressed in the adult brain, focusing on

Long-term outcome after arterial ischemic stroke in children and young adults.

Science.gov (United States)

Goeggel Simonetti, Barbara; Cavelti, Ariane; Arnold, Marcel; Bigi, Sandra; Regényi, Mária; Mattle, Heinrich P; Gralla, Jan; Fluss, Joel; Weber, Peter; Hackenberg, Annette; Steinlin, Maja; Fischer, Urs

2015-05-12

To compare long-term outcome of children and young adults with arterial ischemic stroke (AIS) from 2 large registries. Prospective cohort study comparing functional and psychosocial long-term outcome (≥2 years after AIS) in patients who had AIS during childhood (1 month-16 years) or young adulthood (16.1-45 years) between January 2000 and December 2008, who consented to follow-up. Data of children were collected prospectively in the Swiss Neuropediatric Stroke Registry, young adults in the Bernese stroke database. Follow-up information was available in 95/116 children and 154/187 young adults. Median follow-up of survivors was 6.9 years (interquartile range 4.7-9.4) and did not differ between the groups (p = 0.122). Long-term functional outcome was similar (p = 0.896): 53 (56%) children and 84 (55%) young adults had a favorable outcome (modified Rankin Scale 0-1). Mortality in children was 14% (13/95) and in young adults 7% (11/154) (p = 0.121) and recurrence rate did not differ (p = 0.759). Overall psychosocial impairment and quality of life did not differ, except for more behavioral problems among children (13% vs 5%, p = 0.040) and more frequent reports of an impact of AIS on everyday life among adults (27% vs 64%, p Stroke Scale/NIH Stroke Scale score was the most important predictor of favorable outcome (p young adults for mortality, disability, quality of life, psychological, or social variables. © 2015 American Academy of Neurology.

The role of additive neurogenesis and synaptic plasticity in a hippocampal memory model with grid-cell like input.

Directory of Open Access Journals (Sweden)

Peter A Appleby

Full Text Available Recently, we presented a study of adult neurogenesis in a simplified hippocampal memory model. The network was required to encode and decode memory patterns despite changing input statistics. We showed that additive neurogenesis was a more effective adaptation strategy compared to neuronal turnover and conventional synaptic plasticity as it allowed the network to respond to changes in the input statistics while preserving representations of earlier environments. Here we extend our model to include realistic, spatially driven input firing patterns in the form of grid cells in the entorhinal cortex. We compare network performance across a sequence of spatial environments using three distinct adaptation strategies: conventional synaptic plasticity, where the network is of fixed size but the connectivity is plastic; neuronal turnover, where the network is of fixed size but units in the network may die and be replaced; and additive neurogenesis, where the network starts out with fewer initial units but grows over time. We confirm that additive neurogenesis is a superior adaptation strategy when using realistic, spatially structured input patterns. We then show that a more biologically plausible neurogenesis rule that incorporates cell death and enhanced plasticity of new granule cells has an overall performance significantly better than any one of the three individual strategies operating alone. This adaptation rule can be tailored to maximise performance of the network when operating as either a short- or long-term memory store. We also examine the time course of adult neurogenesis over the lifetime of an animal raised under different hypothetical rearing conditions. These growth profiles have several distinct features that form a theoretical prediction that could be tested experimentally. Finally, we show that place cells can emerge and refine in a realistic manner in our model as a direct result of the sparsification performed by the dentate gyrus

Long-Term Visual Training Increases Visual Acuity and Long-Term Monocular Deprivation Promotes Ocular Dominance Plasticity in Adult Standard Cage-Raised Mice.

Science.gov (United States)

Hosang, Leon; Yusifov, Rashad; Löwel, Siegrid

2018-01-01

For routine behavioral tasks, mice predominantly rely on olfactory cues and tactile information. In contrast, their visual capabilities appear rather restricted, raising the question whether they can improve if vision gets more behaviorally relevant. We therefore performed long-term training using the visual water task (VWT): adult standard cage (SC)-raised mice were trained to swim toward a rewarded grating stimulus so that using visual information avoided excessive swimming toward nonrewarded stimuli. Indeed, and in contrast to old mice raised in a generally enriched environment (Greifzu et al., 2016), long-term VWT training increased visual acuity (VA) on average by more than 30% to 0.82 cycles per degree (cyc/deg). In an individual animal, VA even increased to 1.49 cyc/deg, i.e., beyond the rat range of VAs. Since visual experience enhances the spatial frequency threshold of the optomotor (OPT) reflex of the open eye after monocular deprivation (MD), we also quantified monocular vision after VWT training. Monocular VA did not increase reliably, and eye reopening did not initiate a decline to pre-MD values as observed by optomotry; VA values rather increased by continued VWT training. Thus, optomotry and VWT measure different parameters of mouse spatial vision. Finally, we tested whether long-term MD induced ocular dominance (OD) plasticity in the visual cortex of adult [postnatal day (P)162-P182] SC-raised mice. This was indeed the case: 40-50 days of MD induced OD shifts toward the open eye in both VWT-trained and, surprisingly, also in age-matched mice without VWT training. These data indicate that (1) long-term VWT training increases adult mouse VA, and (2) long-term MD induces OD shifts also in adult SC-raised mice.

From network structure to network reorganization: implications for adult neurogenesis

International Nuclear Information System (INIS)

Schneider-Mizell, Casey M; Zochowski, Michal R; Sander, Leonard M; Parent, Jack M; Ben-Jacob, Eshel

2010-01-01

Networks can be dynamical systems that undergo functional and structural reorganization. One example of such a process is adult hippocampal neurogenesis, in which new cells are continuously born and incorporate into the existing network of the dentate gyrus region of the hippocampus. Many of these introduced cells mature and become indistinguishable from established neurons, joining the existing network. Activity in the network environment is known to promote birth, survival and incorporation of new cells. However, after epileptogenic injury, changes to the connectivity structure around the neurogenic niche are known to correlate with aberrant neurogenesis. The possible role of network-level changes in the development of epilepsy is not well understood. In this paper, we use a computational model to investigate how the structural and functional outcomes of network reorganization, driven by addition of new cells during neurogenesis, depend on the original network structure. We find that there is a stable network topology that allows the network to incorporate new neurons in a manner that enhances activity of the persistently active region, but maintains global network properties. In networks having other connectivity structures, new cells can greatly alter the distribution of firing activity and destroy the initial activity patterns. We thus find that new cells are able to provide focused enhancement of network only for small-world networks with sufficient inhibition. Network-level deviations from this topology, such as those caused by epileptogenic injury, can set the network down a path that develops toward pathological dynamics and aberrant structural integration of new cells

Adult neurogenesis in the central olfactory pathway of dendrobranchiate and caridean shrimps: New insights into the evolution of the deutocerebral proliferative system in reptant decapods.

Science.gov (United States)

Wittfoth, Christin; Harzsch, Steffen

2018-04-16

Persistent neurogenesis in the central olfactory pathway characterizes many reptant decapods such as lobsters, crayfish and crabs. In these animals, the deutocerebral proliferative system generates new neurons which integrate into the neuronal network of the first order processing neuropil of the olfactory system, the deutocerebral chemosensory lobes (also called olfactory lobes). However, differences concerning the phenotype and the mechanisms that drive adult neurogenesis were reported in crayfish versus spiny lobsters. While numerous studies have focussed on these mechanisms and regulation of adult neurogenesis, investigations about the phylogenetic distribution are missing. To contribute an evolutionary perspective on adult neurogenesis in decapods, we investigated two representatives of basally diverging lineages, the dendrobranchiate Penaeus vannamei and the caridean Crangon crangon using the thymidine analogue Bromodeoxyuridine (BrdU) as marker for the S phase of cycling cells. Compared to reptant decapods, our results suggest a simpler mechanism of neurogenesis in the adult brain of dendrobranchiate and caridean shrimps. Observed differences in the rate of proliferation and spatial dimensions are suggested to correlate with the complexity of the olfactory system. We assume that a more complex and mitotically more active proliferative system in reptant decapods evolved with the emergence of another processing neuropil, the accessory lobes. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Dentate Gyrus Neurogenesis, Integration, and microRNAs

OpenAIRE

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

2011-01-01

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

Memory-enhancing effects of Cuscuta japonica Choisy via enhancement of adult hippocampal neurogenesis in mice.

Science.gov (United States)

Moon, Minho; Jeong, Hyun Uk; Choi, Jin Gyu; Jeon, Seong Gak; Song, Eun Ji; Hong, Seon-Pyo; Oh, Myung Sook

2016-09-15

It is generally accepted that functional and structural changes within the hippocampus are involved in learning and memory and that adult neurogenesis in this region may modulate cognition. The extract of Cuscuta japonica Choisy (CJ) is a well-known traditional Chinese herbal medicine that has been used since ancient times as a rejuvenation remedy. The systemic effects of this herb are widely known and can be applied for the treatment of a number of physiological diseases, but there is a lack of evidence describing its effects on brain function. Thus, the present study investigated whether CJ would enhance memory function and/or increase hippocampal neurogenesis using mice orally administered with CJ water extract or vehicle for 21days. Performance on the novel object recognition and passive avoidance tests revealed that treatment with CJ dose-dependently improved the cognitive function of mice. Additionally, CJ increased the Ki-67-positive proliferating cells and the number of doublecortin-stained neuroblasts in the dentate gyrus (DG) of the hippocampus, and double labeling with 5-bromo-2-deoxyuridine and neuronal specific nuclear protein showed that CJ increased the number of mature neurons in the DG. Finally, CJ resulted in the upregulated expression of neurogenic differentiation factor, which is essential for the maturation and differentiation of granule cells in the hippocampus. Taken together, the present findings indicate that CJ stimulated neuronal cell proliferation, differentiation, and maturation, which are all processes associated with neurogenesis. Additionally, these findings suggest that CJ may improve learning and memory via the enhancement of adult hippocampal neurogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Personality and psychological distress among older adult, long-term cancer survivors.

Science.gov (United States)

Deimling, Gary T; Albitz, Casey; Monnin, Kara; Renzhofer Pappada, Holly T; Nalepa, Elizabeth; Boehm, Melinda Laroco; Mitchell, Claire

2017-01-01

This research examines a model of how personality (Five-Factor Model) is related to adjustment to cancer in later life in terms of the presence of continuing cancer-related worry and depression among older adult, long-term cancer survivors. Data from an NCI-funded study with 275 older adult (age 60+), long-term (5+ years) survivors of breast, prostate, and colorectal cancer were examined. Regression analyses identified neuroticism as the strongest predictor of cancer-related worry along with continuing cancer-related symptoms. For depression, three personality dimensions (neuroticism, conscientiousness, and agreeableness) were significant predictors. Findings suggest the importance of considering the central role that survivors' personality characteristics play in understanding cancer-related worries and depression. Understanding these dispositional characteristics is key for social workers and health-care practitioners in counseling survivors experiencing these common mental health effects.

Adult Neurogenesis in the Hippocampus From a Perspective of Discrimination and Generalization: A Hypothesis

Czech Academy of Sciences Publication Activity Database

Pištíková, Adéla; Brožka, Hana; Stuchlík, Aleš

2017-01-01

Roč. 66, č. 3 (2017), s. 441-448 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA17-04047S Institutional support: RVO:67985823 Keywords : adult neurogenesis * function * discrimination * generalization * spatial memory * pattern separation Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

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

Directory of Open Access Journals (Sweden)

Orly eLazarov

2013-08-01

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

Neurogenesis dan Faktor-Faktor yang Berpengaruh

Directory of Open Access Journals (Sweden)

Ria Puspitawati

2015-09-01

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

[Falls and fractures among older adults living in long-term care].

Science.gov (United States)

Del Duca, Giovâni Firpo; Antes, Danielle Ledur; Hallal, Pedro Curi

2013-03-01

To investigate the prevalence of falls and fractures over the past 12 months and associated factors among older adults living in long-term care. Census of all long-term care located in the city of Pelotas, Brazil, in 2008. Falls over the past 12 months were assessed using the following question: "Over the last 12 months, have you fallen?" For those who replied positively, another question was asked: "In any of these falls, have you fractured a bone?" Sex, age, schooling, disability relating to basic activities of daily living, type of financing of the long-term care and hospital admissions were the independent variables. We used chi-square tests for heterogeneity and linear trend in the unadjusted analysis, and Poisson regression with robust variance in the adjusted one. Within the 24 long-term care studied, we collected data for 466 individuals. The prevalence of falls in the past year was 38.9% (95%CI 34.5; 43.4). Among those who have fallen, 19.2% had fractures. Femur (hip) was the most frequent site fractured (43.4%), followed by wrist (10%). In the adjusted analysis, older age, disability for 1-5 basic activities of daily living, living in public institutions and hospital admissions in the last year were associated with higher risk of falls. The high prevalence of falls and fractures highlights the fragility of the individuals living in long-term care. Special attention should be paid to older adults and those with hospital admissions in the last year.

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

Directory of Open Access Journals (Sweden)

Ryan P. Vetreno

2018-03-01

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

Ongoing neurogenesis in the adult dentate gyrus mediates behavioral responses to ambiguous threat cues.

Directory of Open Access Journals (Sweden)

Lucas R Glover

2017-04-01

Full Text Available Fear learning is highly adaptive if utilized in appropriate situations but can lead to generalized anxiety if applied too widely. A role of predictive cues in inhibiting fear generalization has been suggested by stress and fear learning studies, but the effects of partially predictive cues (ambiguous cues and the neuronal populations responsible for linking the predictive ability of cues and generalization of fear responses are unknown. Here, we show that inhibition of adult neurogenesis in the mouse dentate gyrus decreases hippocampal network activation and reduces defensive behavior to ambiguous threat cues but has neither of these effects if the same negative experience is reliably predicted. Additionally, we find that this ambiguity related to negative events determines their effect on fear generalization, that is, how the events affect future behavior under novel conditions. Both new neurons and glucocorticoid hormones are required for the enhancement of fear generalization following an unpredictably cued threat. Thus, adult neurogenesis plays a central role in the adaptive changes resulting from experience involving unpredictable or ambiguous threat cues, optimizing behavior in novel and uncertain situations.

Post-stroke epilepsy in young adults: a long-term follow-up study

NARCIS (Netherlands)

Arntz, R.M.; Rutten-Jacobs, L.C.A.; Maaijwee, N.A.M.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Dijk, E.J. van; Leeuw, F.E. de

2013-01-01

BACKGROUND: Little is known about the incidence and risk of seizures after stroke in young adults. Especially in the young seizures might dramatically influence prognosis and quality of life. We therefore investigated the long-term incidence and risk of post-stroke epilepsy in young adults with a

Factors That Modulate Neurogenesis: A Top-Down Approach.

Science.gov (United States)

LaDage, Lara D

2016-08-24

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

Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal

Science.gov (United States)

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

2011-01-01

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

Neurogenesis and brain injury: managing a renewable resource for repair

OpenAIRE

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

2003-01-01

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

TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

Science.gov (United States)

Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

2013-12-15

TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

Role of adult neurogenesis in hippocampal-cortical memory consolidation

Science.gov (United States)

2014-01-01

Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

Impact of long-term HPN on daily life in adults.

NARCIS (Netherlands)

Persoon, A.; Huisman-de Waal, G.J.; Naber, A.H.J.; Schoonhoven, L.; Tas, T.; Sauerwein, H.P.; Achterberg, T. van

2005-01-01

BACKGROUND AND AIMS: Home parenteral nutrition (HPN) is a therapy that changes life radically and often means lifelong dependence on parenteral feeding. The aim of this study was to gain insight into problems experienced by adult patients who were dependent on long-term HPN. METHODS: A survey was

The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro.

Science.gov (United States)

Morales-García, Jose A; de la Fuente Revenga, Mario; Alonso-Gil, Sandra; Rodríguez-Franco, María Isabel; Feilding, Amanda; Perez-Castillo, Ana; Riba, Jordi

2017-07-13

Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches.

The effect of hypertension on adult hippocampal neurogenesis in young adult spontaneously hypertensive rats and Dahl rats

Czech Academy of Sciences Publication Activity Database

Pištíková, Adéla; Brožka, Hana; Bencze, Michal; Radostová, Dominika; Valeš, Karel; Stuchlík, Aleš

2017-01-01

Roč. 66, č. 5 (2017), s. 881-887 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GBP304/12/G069 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : adult neurogenesis * Captopril * hypertension * Dahl rats * SHR * young animals Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

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

Science.gov (United States)

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

2013-11-01

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

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

Directory of Open Access Journals (Sweden)

Jin Young Shin

-mediated ERK signaling pathway. CONCLUSIONS/SIGNIFICANCE: Modulation of levodopa-induced elevated homocysteine by NMDA antagonist or dopamine agonist has a clinical relevance for PD treatment in terms of adult neurogenesis.

Maintaining appearances-The role of p53 in adult neurogenesis

International Nuclear Information System (INIS)

Medrano, Silvia; Scrable, Heidi

2005-01-01

In the adult mammalian brain, neuronal turnover continues to replenish cells in existing neuronal circuits, such as those involved either in odor discrimination or in learning and memory, throughout life. With age, however, the capacity for neurogenesis diminishes and these functions become impaired. Neuronal turnover is a two-step process, which first generates excess neuronal progenitors and then eliminates all but the few that differentiate into fully functional neurons. This process requires a fine balance between cell proliferation and cell death. Altered activity of the tumor suppressor p53 can upset this balance by affecting the rate of cell proliferation, but not the rate of cell death, in neurogenic regions of the adult brain. Genetically engineered mice in which p53 activity is increased demonstrate that premature loss of neurogenic capacity is linked to accelerated organismal aging

Low- and High-Resistance Exercise: Long-Term Adherence and Motivation among Older Adults.

Science.gov (United States)

Van Roie, Evelien; Bautmans, Ivan; Coudyzer, Walter; Boen, Filip; Delecluse, Christophe

2015-01-01

In terms of motivation and long-term adherence, low-resistance exercise might be more suitable for older adults than high-resistance exercise. However, more data are needed to support this claim. The objective was to investigate the effect of low- and high-resistance exercise protocols on long-term adherence and motivation. This study was designed as an exploratory 24-week follow-up of a randomized 12-week resistance training intervention in older adults. Participants were free to decide whether or not they continued resistance training at their own expense following the intervention. Fifty-six older adults were randomly assigned to HIGH [2 × 10-15 repetitions at 80% of one repetition maximum (1RM)], LOW (1 × 80-100 repetitions at 20% of 1RM), or LOW+ (1 × 60 repetitions at 20% of 1RM + 1 × 10-20 repetitions at 40% 1RM). Motivation, self-efficacy and the perceived barriers for continuing resistance exercise were measured after cessation of each supervised intervention and at follow-up, while long-term adherence was probed retrospectively at follow-up. Participants reported high levels of self-determined motivation before, during, and after the supervised intervention, with no differences between groups (p > 0.05). Nevertheless, only few participants continued strength training after the intervention: 17% in HIGH, 21% in LOW+, and 11% in LOW (p > 0.05). The most commonly reported barriers for continuing resistance exercise were perceived lack of time (46%), being more interested in other physical activities (40%), seasonal reasons (40%), and financial cost (28%). The results suggest no difference in long-term adherence after the end of a supervised exercise intervention at high or low external resistances. Long-term adherence was limited despite high levels of self-determined motivation during the interventions. These findings highlight the importance of further research on developing strategies to overcome barriers of older adults to adhere to resistance

Impact of long-term HPN on daily life in adults

NARCIS (Netherlands)

Persoon, Anke; Huisman-de Waal, Getty; Naber, Ton A.; Schoonhoven, Lisette; Tas, Tirzah; Sauerwein, Hans; van Achterberg, Theo

2005-01-01

Home parenteral nutrition (HPN) is a therapy that changes life radically and often means lifelong dependence on parenteral feeding. The aim of this study was to gain insight into problems experienced by adult patients who were dependent on long-term HPN. A survey was performed on all patients at the

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

Directory of Open Access Journals (Sweden)

Kiran eTodkar

2012-04-01

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

The Circadian Molecular Clock Regulates Adult Hippocampal Neurogenesis by Controlling the Timing of Cell-Cycle Entry and Exit

Directory of Open Access Journals (Sweden)

Pascale Bouchard-Cannon

2013-11-01

Full Text Available The subgranular zone (SGZ of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adult SGZ express molecular-clock components and proliferate in a rhythmic fashion. The clock proteins PERIOD2 and BMAL1 are critical for proper control of neurogenesis. The absence of PERIOD2 abolishes the gating of cell-cycle entrance of QNPs, whereas genetic ablation of bmal1 results in constitutively high levels of proliferation and delayed cell-cycle exit. We use mathematical model simulations to show that these observations may arise from clock-driven expression of a cell-cycle inhibitor that targets the cyclin D/Cdk4-6 complex. Our findings may have broad implications for the circadian clock in timing cell-cycle events of other stem cell populations throughout the body.

Reproductive status in adult male long-term survivors of childhood cancer

NARCIS (Netherlands)

Tromp, K.; Claessens, J. J. M.; Knijnenburg, S. L.; van der Pal, H. J. H.; van Leeuwen, F. E.; Caron, H. N.; Beerendonk, C. C. M.; Kremer, L. C. M.

2011-01-01

This study assessed the long-term effects of cancer therapies on reproductive status in adult male childhood cancer survivors, evaluated the treatment-related risk factors for hypergonadotropic hypogonadism and assessed the association between the FSH levels and the later need for assisted

Reproductive status in adult male long-term survivors of childhood cancer

NARCIS (Netherlands)

Tromp, K.; Claessens, J.J.M.; Knijnenburg, S.L.; Pal, H.J. van der; Leeuwen, F.E. van; Caron, H.N.; Beerendonk, C.C.M.; Kremer, L.C.

2011-01-01

BACKGROUND: This study assessed the long-term effects of cancer therapies on reproductive status in adult male childhood cancer survivors, evaluated the treatment-related risk factors for hypergonadotropic hypogonadism and assessed the association between the FSH levels and the later need for

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

Directory of Open Access Journals (Sweden)

Jeremy D. Coplan

2014-01-01

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

Major unsolved points in adult neurogenesis: doors open on a translational future?

Directory of Open Access Journals (Sweden)

Paolo ePeretto

2014-06-01

Full Text Available The ultimate goal of exploiting adult neurogenesis (AN as a source of cell replacement is far from being achieved. In spite of many data gathered during the last two decades on homeostatic and reactive neurogenesis, it is evident that such knowledge is not sufficient for granting translational outcomes. By asking the question whether AN research field has to be considered as a dead end in such a perspective, here we review some major unresolved issues: multifaceted evolutionary constraints emerged in mammals, stem/progenitor cell type/availability and tissue permissivity, the possible impact on other brain functions and/or interplay with other forms of plasticity, and relevance in humans. We suggest that full understanding of AN biological processes is an essential step to their possible exploitation for brain repair, and that further fundamental, multidisciplinary research is required before translational outcomes can be reached. Scientist's attitude and their communication skills are also important. To avoid overestimation of AN reparative potential, more distant goals of cell replacement should be kept clearly distinct from restorative approaches involving AN plasticity, both representing translational perspectives.

Long-term cognitive impairment after first-ever ischemic stroke in young adults.

Science.gov (United States)

Schaapsmeerders, Pauline; Maaijwee, Noortje A M; van Dijk, Ewoud J; Rutten-Jacobs, Loes C A; Arntz, Renate M; Schoonderwaldt, Hennie C; Dorresteijn, Lucille D A; Kessels, Roy P C; de Leeuw, Frank-Erik

2013-06-01

Up to 14% of all ischemic strokes occur in young adults (young stroke, especially not on the long term. This long-term perspective is important because young patients have a long life expectancy during which they start forming a family, have an active social life, and make decisive career moves. We aimed to evaluate the long-term cognitive outcome. All consecutive patients between January 1, 1980, and November 1, 2010, with a first-ever young ischemic stroke were recruited for cognitive assessment, using a matched stroke-free population as a reference. Composite Z scores for 7 cognitive domains were calculated and the ANCOVA model was used (Bonferroni correction). A below average performance was defined as >1.0 SD below the age-adjusted mean of the controls and cognitive impairment as >1.5 SD. Two hundred seventy-seven patients and 146 matched controls completed cognitive assessment (mean follow-up, 11.0 years, SD, 8.2; age, 50.9 years, SD, 10.3). Long-term cognitive outcome after an ischemic stroke was worse in most cognitive domains compared with a nonstroke population. Up to 50% of the patients had a below average performance or cognitive impairment. Deficits in processing speed, working memory, and attention were most common. Even 11 years after ischemic stroke in young adults, a substantial proportion of patients must cope with permanent cognitive deficits. These results have implications for information given to patients and rehabilitation services.

Neurogenesis in the septal and temporal part of the adult rat dentate gyrus.

Science.gov (United States)

Bekiari, Chryssa; Giannakopoulou, Aggeliki; Siskos, Nikistratos; Grivas, Ioannis; Tsingotjidou, Anastasia; Michaloudi, Helen; Papadopoulos, Georgios C

2015-04-01

Structural and functional dissociation between the septal and the temporal part of the dentate gyrus predispose for possible differentiations in the ongoing neurogenesis process of the adult hippocampus. In this study, BrdU-dated subpopulations of the rat septal and temporal dentate gyrus (coexpressing GFAP, DCX, NeuN, calretinin, calbindin, S100, caspase-3 or fractin) were quantified comparatively at 2, 5, 7, 14, 21, and 30 days after BrdU administration in order to examine the successive time-frames of the neurogenesis process, the glial or neuronal commitment of newborn cells and the occurring apoptotic cell death. Newborn neurons' migration from the neurogenic subgranular zone to the inner granular cell layer and expression of glutamate NMDA and AMPA receptors were also studied. BrdU immunocytochemistry revealed comparatively higher numbers of BrdU(+) cells in the septal part, but stereological analysis of newborn and total granule cells showed an identical ratio in the two parts, indicating an equivalent neurogenic ability, and a common topographical pattern along each part's longitudinal and transverse axis. Similarly, both parts exhibited extremely low levels of newborn glial and apoptotic cells. However, despite the initially equal division rate and pattern of the septal and temporal proliferating cells, their later proliferative profile diverged in the two parts. Dynamic differences in the differentiation, migration and maturation process of the two BrdU-incorporating subpopulations of newborn neurons were also detected, along with differences in their survival pattern. Therefore, we propose that various factors, including developmental date birth, local DG microenvironment and distinct functionality of the two parts may be the critical regulators of the ongoing neurogenesis process, leading the septal part to a continuous, rapid, and less-disciplined genesis rate, whereas the quiescent temporal microenvironment preserves a quite steady, less

Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

Science.gov (United States)

Furuta, Miyako; Bridges, Robert S.

2009-01-01

The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain

Directory of Open Access Journals (Sweden)

Vanesa eNieto-Estévez

2016-02-01

Full Text Available The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs. This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP and the subventricular zone-olfactory bulb (SVZ-OB. By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also, by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis and neuron integration in synaptic circuits.

IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

Science.gov (United States)

Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

2016-01-01

The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

Enhanced post-ischemic neurogenesis in aging rats

Directory of Open Access Journals (Sweden)

Yao-Fang Tan

2010-08-01

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

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

Directory of Open Access Journals (Sweden)

Ansorg Anne

2012-05-01

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

Adult neurogenesis reduction by a cytostatic treatment improves spatial reversal learning in rats

Czech Academy of Sciences Publication Activity Database

Brožka, Hana; Pištíková, Adéla; Radostová, Dominika; Valeš, Karel; Svoboda, Jan; Grzyb, A. N.; Stuchlík, Aleš

2017-01-01

Roč. 141, May (2017), s. 93-100 ISSN 1074-7427 R&D Projects: GA ČR(CZ) GA14-03627S; GA MŠk(CZ) LH14053 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : active avoidance * hippocampus * adult neurogenesis * discrimination * generalization * reversal Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 3.543, year: 2016

On the Role of Neurogenesis and Neural Plasticity in the Evolution of Animal Personalities and Stress Coping Styles

DEFF Research Database (Denmark)

Overli, Oyvind; Sorensen, Christina

2016-01-01

and neurogenesis have received recent attention. This work reveals that brain cell proliferation and neurogenesis are associated with heritable variation in stress coping style, and they are also differentially affected by short- and long-term stress in a biphasic manner. Routine-dependent and inflexible behavior...... are conserved throughout the vertebrate subphylum, including factors affecting perception, learning, and memory of stimuli and events. Here we review conserved aspects of the contribution of neurogenesis and other aspects of neural plasticity to stress coping. In teleost fish, brain cell proliferation...

Sexuality and Physical Intimacy in Long Term Care: Sexuality, long term care, capacity assessment

OpenAIRE

Lichtenberg, Peter A.

2014-01-01

Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literatur...

Long-term survival of adult trauma patients.

Science.gov (United States)

Davidson, Giana H; Hamlat, Christian A; Rivara, Frederick P; Koepsell, Thomas D; Jurkovich, Gregory J; Arbabi, Saman

2011-03-09

Inpatient trauma case fatality rates may provide an incomplete assessment for overall trauma care effectiveness. To date, there have been few large studies evaluating long-term mortality in trauma patients and identifying predictors that increase risk for death following hospital discharge. To determine the long-term mortality of patients following trauma admission and to evaluate survivorship in relationship with discharge disposition. Retrospective cohort study of 124,421 injured adult patients during January 1995 to December 2008 using the Washington State Trauma Registry linked to death certificate data. Kaplan-Meier and Cox proportional hazards models were used to evaluate long-term mortality following hospital admission for trauma. Of the 124,421 trauma patients, 7243 died before hospital discharge and 21,045 died following hospital discharge. Cumulative mortality at 3 years postinjury was 16% (95% confidence interval [CI], 15.8%-16.2%) compared with the expected population cumulative mortality of 5.9% (95% CI, 5.9%-5.9%). In-hospital mortality improved during the 14-year study period from 8% (n = 362) to 4.9% (n = 600), whereas long-term cumulative mortality increased from 4.7% (95% CI, 4.1%-5.4%) to 7.4% (95% CI, 6.8%-8.1%). After adjustments for confounders, patients who were older and those who were discharged to a skilled nursing facility had the highest risk of death. The adjusted hazard ratios (HRs) for death after discharge to a skilled nursing facility compared with that after discharge home were 1.41 (95% CI, 0.72-2.76) for patients aged 18 to 30 years, 1.92 (95% CI, 1.36-2.73) for patients aged 31 to 45 years, 2.02 (95% CI, 1.39-2.93) for patients aged 46 to 55 years, 1.93 (95% CI, 1.40-2.64) for patients aged 56 to 65 years, 1.49 (95% CI, 1.14-1.94) for patients aged 66 to 75 years, 1.54 (95% CI, 1.27-1.87) for patients aged 76 to 80 years, and 1.38 (95% CI, 1.09-1.74) for patients older than 80 years. Other significant predictors of mortality

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

NARCIS (Netherlands)

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

2017-01-01

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

Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

Science.gov (United States)

López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

2016-01-01

Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

The circadian molecular clock regulates adult hippocampal neurogenesis by controlling the timing of cell-cycle entry and exit.

Science.gov (United States)

Bouchard-Cannon, Pascale; Mendoza-Viveros, Lucia; Yuen, Andrew; Kærn, Mads; Cheng, Hai-Ying M

2013-11-27

The subgranular zone (SGZ) of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs) that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adult SGZ express molecular-clock components and proliferate in a rhythmic fashion. The clock proteins PERIOD2 and BMAL1 are critical for proper control of neurogenesis. The absence of PERIOD2 abolishes the gating of cell-cycle entrance of QNPs, whereas genetic ablation of bmal1 results in constitutively high levels of proliferation and delayed cell-cycle exit. We use mathematical model simulations to show that these observations may arise from clock-driven expression of a cell-cycle inhibitor that targets the cyclin D/Cdk4-6 complex. Our findings may have broad implications for the circadian clock in timing cell-cycle events of other stem cell populations throughout the body. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Cognitive side effects of cancer therapy demonstrate a functional role for adult neurogenesis.

Science.gov (United States)

Monje, Michelle; Dietrich, Jörg

2012-02-14

Cancer therapies frequently result in a spectrum of neurocognitive deficits that include impaired learning, memory, attention and speed of information processing. Damage to dynamic neural progenitor cell populations in the brain are emerging as important etiologic factors. Radiation and chemotherapy-induced damage to neural progenitor populations responsible for adult hippocampal neurogenesis and for maintenance of subcortical white matter integrity are now believed to play major roles in the neurocognitive impairment many cancer survivors experience. Copyright © 2011 Elsevier B.V. All rights reserved.

Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD

Science.gov (United States)

Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

2009-01-01

Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

Running wheel training does not change neurogenesis levels or alter working memory tasks in adult rats

Directory of Open Access Journals (Sweden)

Cesar A. Acevedo-Triana

2017-05-01

Full Text Available Background Exercise can change cellular structure and connectivity (neurogenesis or synaptogenesis, causing alterations in both behavior and working memory. The aim of this study was to evaluate the effect of exercise on working memory and hippocampal neurogenesis in adult male Wistar rats using a T-maze test. Methods An experimental design with two groups was developed: the experimental group (n = 12 was subject to a forced exercise program for five days, whereas the control group (n = 9 stayed in the home cage. Six to eight weeks after training, the rats’ working memory was evaluated in a T-maze test and four choice days were analyzed, taking into account alternation as a working memory indicator. Hippocampal neurogenesis was evaluated by means of immunohistochemistry of BrdU positive cells. Results No differences between groups were found in the behavioral variables (alternation, preference index, time of response, time of trial or feeding, or in the levels of BrdU positive cells. Discussion Results suggest that although exercise may have effects on brain structure, a construct such as working memory may require more complex changes in networks or connections to demonstrate a change at behavioral level.

Health and participation problems in older adults with long-term disability.

Science.gov (United States)

Hilberink, Sander R; van der Slot, Wilma M A; Klem, Martijn

2017-04-01

More attention and understanding of the health and participation problems of adults with early and later onset disabilities in the Netherlands is needed. To explore health/participation problems and unmet needs in adults aged ≥40 years with long-term disabilities and their relationship with the time of onset. Participants were recruited in the Netherlands through newsletters and social media to participate in a web-based questionnaire. The questionnaire assessed background characteristics, (change in) health/participation problems, and unmet needs. Spearman's rho was used to examine the relationships with time of onset. Of the 163 survey respondents, 42% acquired their disability before age 25 years and reported fatigue (77%), walking problems (66%), and pain (59%). In 21% of the respondents with early-onset disability fatigue, pain and depressive feelings co-occurred. Early-onset disability correlated with joint deformities, pain and anxiety. Participation problems included loss of income and fewer social activities. Early-onset correlated with the need for more information about diagnosis and prognosis. People aged over 40 years with long-term disability have significant and increasing health and participation problems. Adults with early-onset disability are more likely to have health or participation problems than adults with late-onset disability. Early identification is needed for preventive care and access to specialized services that focus on improving and maintaining physical symptoms, energy management, and participation. Copyright © 2016 Elsevier Inc. All rights reserved.

Temporal Discontiguity Is neither Necessary nor Sufficient for Learning-Induced Effects on Adult Neurogenesis

Science.gov (United States)

Leuner, Benedetta; Waddell, Jaylyn; Gould, Elizabeth; Shors, Tracey J.

2012-01-01

Some, but not all, types of learning and memory can influence neurogenesis in the adult hippocampus. Trace eyeblink conditioning has been shown to enhance the survival of new neurons, whereas delay eyeblink conditioning has no such effect. The key difference between the two training procedures is that the conditioning stimuli are separated in time during trace but not delay conditioning. These findings raise the question of whether temporal discontiguity is necessary for enhancing the survival of new neurons. Here we used two approaches to test this hypothesis. First, we examined the influence of a delay conditioning task in which the duration of the conditioned stimulus (CS) was increased nearly twofold, a procedure that critically engages the hippocampus. Although the CS and unconditioned stimulus are contiguous, this very long delay conditioning procedure increased the number of new neurons that survived. Second, we examined the influence of learning the trace conditioned response (CR) after having acquired the CR during delay conditioning, a procedure that renders trace conditioning hippocampal-independent. In this case, trace conditioning did not enhance the survival of new neurons. Together, these results demonstrate that associative learning increases the survival of new neurons in the adult hippocampus, regardless of temporal contiguity. PMID:17192426

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

Directory of Open Access Journals (Sweden)

Sebastian R Schreglmann

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

Impact of glucocorticoid on neurogenesis

Directory of Open Access Journals (Sweden)

Haruki Odaka

2017-01-01

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

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

Directory of Open Access Journals (Sweden)

Jesse Daniel Cushman

2012-02-01

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

Should frail older adults be in long-term care facilities?

Directory of Open Access Journals (Sweden)

Sørbye LW

2018-02-01

Full Text Available Liv Wergeland Sørbye, Sidsel Sverdrup, Birgit Brunborg Pay Institute of Nursing and Health, VID Specialized University, Oslo, Norway Aim: Home-based nursing care is relatively easy to access in Norway compared to the rest of Europe, and the threshold for applying for assistance is relatively low. The aim of the present study was to analyze factors that enable frail older adults to live in their own homes, with a low level of care burden stress.Methodology: In 2015 and 2016, eight municipalities from different parts of Norway participated in a cross-sectional study. The quantitative part of the project consisted of assessing care of 71 older adults, aged ≥80 years, using a geriatric comprehensive assessment. The qualitative part consisted of semistructured telephone interviews with 14 leaders of nursing homes and home-based nursing care and interviews with 26 close relatives.Results: In this sample, 60% of the older adults were living alone, and 79% were at risk of permanent nursing home admission; 31% stated that they would be better-off at a higher caring level, mainly due to living alone. The relatives, their resources, and motivation to provide care seemed to be crucial for how long older adults with heavy care burden could stay at home. The municipalities offered a combination of comprehensive home care, day centers, and revolving short-term stays to enable them to live at home.Conclusion: The results reveal that the need for home care services is steadily increasing. The relatives are coping with the physical care, far better than the uncertainties and worries about what could happen when the older adults stay alone. The number of beds in institutional care in each municipality depends on various factors, such as the inhabitants’ life expectancy, social aspects, geography, well-functioning eldercare pathways, competence of the health professionals, and a well-planned housing policy. Keywords: home care, geriatric assessment

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

Directory of Open Access Journals (Sweden)

Berry Juliandi

2015-12-01

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

α2δ ligands act as positive modulators of adult hippocampal neurogenesis and prevent depression-like behavior induced by chronic restraint stress.

Science.gov (United States)

Valente, Maria Maddalena; Bortolotto, Valeria; Cuccurazzu, Bruna; Ubezio, Federica; Meneghini, Vasco; Francese, Maria Teresa; Canonico, Pier Luigi; Grilli, Mariagrazia

2012-08-01

Although the role of adult hippocampal neurogenesis remains to be fully elucidated, several studies suggested that the process is involved in cognitive and emotional functions and is deregulated in various neuropsychiatric disorders, including major depression. Several psychoactive drugs, including antidepressants, can modulate adult neurogenesis. Here we show for the first time that the α2δ ligands gabapentin [1-(aminomethyl)cyclohexaneacetic acid] and pregabalin (PGB) [(S)-(+)-3-isobutyl-GABA or (S)-3-(aminomethyl)-5-methylhexanoic acid] can produce concentration-dependent increases in the numbers of newborn mature and immature neurons generated in vitro from adult hippocampal neural progenitor cells and, in parallel, a decrease in the number of undifferentiated precursor cells. These effects were confirmed in vivo, because significantly increased numbers of adult cell-generated neurons were observed in the hippocampal region of mice receiving prolonged treatment with PGB (10 mg/kg i.p. for 21 days), compared with vehicle-treated mice. We demonstrated that PGB administration prevented the appearance of depression-like behaviors induced by chronic restraint stress and, in parallel, promoted hippocampal neurogenesis in adult stressed mice. Finally, we provided data suggesting involvement of the α2δ1 subunit and the nuclear factor-κB signaling pathway in drug-mediated proneurogenic effects. The new pharmacological activities of α2δ ligands may help explain their therapeutic activity as supplemental therapy for major depression and depressive symptoms in post-traumatic stress disorder and generalized anxiety disorders. These data contribute to the identification of novel molecular pathways that may represent potential targets for pharmacological modulation in depression.

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

Data.gov (United States)

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

Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats

OpenAIRE

Klomp, A.; Václavů, L.; Meerhoff, G.F.; Reneman, L.; Lucassen, P.J.

2014-01-01

The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal developm...

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

Directory of Open Access Journals (Sweden)

Kevin T Gobeske

2009-10-01

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

The aPKC-CBP Pathway Regulates Adult Hippocampal Neurogenesis in an Age-Dependent Manner

Directory of Open Access Journals (Sweden)

Ayden Gouveia

2016-10-01

Full Text Available While epigenetic modifications have emerged as attractive substrates to integrate environmental changes into the determination of cell identity and function, specific signals that directly activate these epigenetic modifications remain unknown. Here, we examine the role of atypical protein kinase C (aPKC-mediated Ser436 phosphorylation of CBP, a histone acetyltransferase, in adult hippocampal neurogenesis and memory. Using a knockin mouse strain (CbpS436A in which the aPKC-CBP pathway is deficient, we observe impaired hippocampal neuronal differentiation, maturation, and memory and diminished binding of CBP to CREB in 6-month-old CbpS436A mice, but not at 3 months of age. Importantly, elevation of CREB activity rescues these deficits, and CREB activity is reduced whereas aPKC activity is increased in the murine hippocampus as they age from 3 to 6 months regardless of genotype. Thus, the aPKC-CBP pathway is a homeostatic compensatory mechanism that modulates hippocampal neurogenesis and memory in an age-dependent manner in response to reduced CREB activity.

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

Science.gov (United States)

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

2010-10-01

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

Long term results of pyeloplasty in adults

International Nuclear Information System (INIS)

Tayib, Abdul Malik

2004-01-01

To determine the presenting systems, complications, stone coincidence in adult patients with primary ureteropelvic junction (UPJ) obstruction seen at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. We are also reporting the success rate and long term results of adult pyeloplasty. We reviewed the records of 34 patients who underwent 37 pyeloplasty operations during the period January 1992 through to June 2002. The preoperative radiological diagnosis made by intravenous urogram or renal isotopes scan. We excluded from our study patients with previous history of passage of stones, renal or ureteral surgeries, large renal pelvis stone that may cause UPJ obstruction or abnormalities that may lead to secondry UPJ obstruction such as vesicoureteral reflux. There were 28 male patients and 8 females, their age varied between 16 and 51-years, the mean age was 36.1 years, and 18 (52.9%) patients had concomitant renal stones. Ispsilateral split renal function improved by 3-7% post pyeloplasty in 23 patients, while in one patient the function stayed the same, and in another patient the split function reduced by 4%. T1/2 renal isotopes washout time became less than 15 minutes in 19 patients and less than 20 minutes in 6 patients. Intravenous urogram revealed disappearence of the obstruction at UPJ in 7 patients while in 2 patients it became poorly functioning. Anderson Hynes pyeloplasty is an excellent procedure for treating UPJ obstruction in adults. Our success rate is comparable to the international repoted rates, while our study revealed a higher incidence of concomitant renal stones than the international studies. (author)

Satb2 determines miRNA expression and long-term memory in the adult central nervous system.

Science.gov (United States)

Jaitner, Clemens; Reddy, Chethan; Abentung, Andreas; Whittle, Nigel; Rieder, Dietmar; Delekate, Andrea; Korte, Martin; Jain, Gaurav; Fischer, Andre; Sananbenesi, Farahnaz; Cera, Isabella; Singewald, Nicolas; Dechant, Georg; Apostolova, Galina

2016-11-29

SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress.

Science.gov (United States)

Culig, Luka; Surget, Alexandre; Bourdey, Marlene; Khemissi, Wahid; Le Guisquet, Anne-Marie; Vogel, Elise; Sahay, Amar; Hen, René; Belzung, Catherine

2017-11-01

Major depression is hypothesized to be associated with dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and impairments in adult hippocampal neurogenesis. Adult-born hippocampal neurons are required for several effects of antidepressants and increasing the rate of adult hippocampal neurogenesis (AHN) before exposure to chronic corticosterone is sufficient to protect against its harmful effects on behavior. However, it is an open question if increasing AHN after the onset of chronic stress exposure would be able to rescue behavioral deficits and which mechanisms might be involved in recovery. We investigated this question by using a 10-week unpredictable chronic mild stress (UCMS) model on a transgenic mouse line (iBax mice), in which the pro-apoptotic gene Bax can be inducibly ablated in neural stem cells following Tamoxifen injection, therefore enhancing the survival of newborn neurons in the adult brain. We did not observe any effect of our treatment in non-stress conditions, but we did find that increasing AHN after 2 weeks of UCMS is sufficient to counteract the effects of UCMS on certain behaviors (splash test and changes in coat state) and endocrine levels and thus to display some antidepressant-like effects. We observed that increasing AHN lowered the elevated basal corticosterone levels in mice exposed to UCMS. This was accompanied by a tamoxifen-induced reversal of the lack of stress-induced decrease in neuronal activation in the anteromedial division of the bed nucleus of the stria terminalis (BSTMA) after intrahippocampal dexamethasone infusion, pointing to a possible mechanism through which adult-born neurons might have exerted their effects. Our results contribute to the neurogenesis hypothesis of depression by suggesting that increasing AHN may be beneficial not just before, but also after exposure to stress by counteracting several of its effects, in part through regulating the HPA axis. Copyright © 2017 Elsevier Ltd. All rights

Newborn neurons in the olfactory bulb selected for long-term survival through olfactory learning are prematurely suppressed when the olfactory memory is erased.

Science.gov (United States)

Sultan, Sébastien; Rey, Nolwen; Sacquet, Joelle; Mandairon, Nathalie; Didier, Anne

2011-10-19

A role for newborn neurons in olfactory memory has been proposed based on learning-dependent modulation of olfactory bulb neurogenesis in adults. We hypothesized that if newborn neurons support memory, then they should be suppressed by memory erasure. Using an ecological approach in mice, we showed that behaviorally breaking a previously learned odor-reward association prematurely suppressed newborn neurons selected to survive during initial learning. Furthermore, intrabulbar infusions of the caspase pan-inhibitor ZVAD (benzyloxycarbonyl-Val-Ala-Asp) during the behavioral odor-reward extinction prevented newborn neurons death and erasure of the odor-reward association. Newborn neurons thus contribute to the bulbar network plasticity underlying long-term memory.

A Diffusion Model Analysis of Adult Age Differences in Episodic and Semantic Long-Term Memory Retrieval

Science.gov (United States)

Spaniol, Julia; Madden, David J.; Voss, Andreas

2006-01-01

Two experiments investigated adult age differences in episodic and semantic long-term memory tasks, as a test of the hypothesis of specific age-related decline in context memory. Older adults were slower and exhibited lower episodic accuracy than younger adults. Fits of the diffusion model (R. Ratcliff, 1978) revealed age-related increases in…

Barriers to and facilitators of long term weight loss maintenance in adult UK people: A thematic analysis

Directory of Open Access Journals (Sweden)

Himanshu Gupta

2014-01-01

Full Text Available Adult obesity and overweight is affecting every region of the world and is described as one of today′s most significant and neglected public health problems. The problem has taken the shape of an epidemic not only because the prevalence of obesity has witnessed a dramatic progress in a short period of time, but also because obesity has paved the way for increased risks for morbidity and mortality associated with it. It has been predicted that about half of the adult men and more than a quarter of adult women would be obese by 2030 in the UK and this figure could rise up to 50% in 2050 for whole of the adult UK population. Although a modest 5-10% weight loss maintained in the long term can significantly decrease health risk, few people engage in weight loss activities. Against this background, this review paper aims to investigate the reasons helping and/or hindering adults in the UK maintain weight loss in the long term; using online and organizational data sources and thematically analyzing the data. Self-body perception, enhanced self-confidence, social support, self-motivation, incentives and rewards, increased physical activity levels and healthy eating habits facilitated people in maintaining weight loss in the long term and overall quality of life. Extreme weather conditions, natural phenomena such as accidents, injuries and ill-health, work commitments, inability for time management and to resist the temptation for food constrained the successful long-term weight loss maintenance.

Long-term health effects of unintentional injuries in Danish adults

DEFF Research Database (Denmark)

Laursen, Bjarne; Møller, Hanne

2012-01-01

INTRODUCTION: The objective of the present study was to determine the prevalence of self-reported health effects of unintentional injuries in the adult Danish population, including the limitation of daily activities and perceived general health. MATERIAL AND METHODS: In the 2005 National Health...... reported poor health in general. The most severe health effects affected the head, neck and back, as well as multiple body parts. Those injuries that entailed the most severe health effects were caused by traffic injuries and falls. CONCLUSION: Long-term effects of injuries are prevalent in the adult...... population and most can be attributed to falls and traffic injuries. Back injuries and multiple injuries had the largest influence on perceived health. FUNDING: The work was supported by TrygFonden grant no. 7585-07. TRIAL REGISTRATION: not relevant....

Very long-term sequelae of craniopharyngioma.

Science.gov (United States)

Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

2017-06-01

Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

Short-term sleep deprivation stimulates hippocampal neurogenesis in rats following global cerebral ischemia/reperfusion.

Directory of Open Access Journals (Sweden)

Oumei Cheng

Full Text Available Sleep deprivation (SD plays a complex role in central nervous system (CNS diseases. Recent studies indicate that short-term SD can affect the extent of ischemic damage. The aim of this study was to investigate whether short-term SD could stimulate hippocampal neurogenesis in a rat model of global cerebral ischemia/reperfusion (GCIR.One hundred Sprague-Dawley rats were randomly divided into Sham, GCIR and short-term SD groups based on different durations of SD; the short-term SD group was randomly divided into three subgroups: the GCIR+6hSD*3d-treated, GCIR+12hSD-treated and GCIR+12hSD*3d-treated groups. The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and hemorrhagic hypotension. The rats were sleep-deprived starting at 48 h following GCIR. A Morris water maze test was used to assess learning and memory ability; cell proliferation and differentiation were analyzed via 5-bromodeoxyuridine (BrdU and neuron-specific enolase (NSE, respectively, at 14 and 28 d; the expression of hippocampal BDNF was measured after 7 d.The different durations of short-term SD designed in our experiment exhibited improvement in cognitive function as well as increased hippocampal BDNF expression. Additionally, the short-term SD groups also showed an increased number of BrdU- and BrdU/NSE-positive cells compared with the GCIR group. Of the three short-term SD groups, the GCIR+12hSD*3d-treated group experienced the most substantial beneficial effects.Short-term SD, especially the GCIR+12hSD*3d-treated method, stimulates neurogenesis in the hippocampal dentate gyrus (DG of rats that undergo GCIR, and BDNF may be an underlying mechanism in this process.

Taxonomic separation of hippocampal networks: principal cell populations and adult neurogenesis

Directory of Open Access Journals (Sweden)

Roelof Maarten evan Dijk

2016-03-01

Full Text Available While many differences in hippocampal anatomy have been described between species, it is typically not clear if they are specific to a particular species and related to functional requirements or if they are shared by species of larger taxonomic units. Without such information, it is difficult to infer how anatomical differences may impact on hippocampal function, because multiple taxonomic levels need to be considered to associate behavioral and anatomical changes. To provide information on anatomical changes within and across taxonomic ranks, we present a quantitative assessment of hippocampal principal cell populations in 20 species or strain groups, with emphasis on rodents, the taxonomic group that provides most animals used in laboratory research. Of special interest is the importance of adult hippocampal neurogenesis in species-specific adaptations relative to other cell populations. Correspondence analysis of cell numbers shows that across taxonomic units, phylogenetically related species cluster together, sharing similar proportions of principal cell populations. CA3 and hilus are strong separators that place rodent species into a tight cluster based on their relatively large CA3 and small hilus while non-rodent species (including humans and non-human primates are placed on the opposite side of the spectrum. Hilus and CA3 are also separators within rodents, with a very large CA3 and rather small hilar cell populations separating mole-rats from other rodents that, in turn, are separated from each other by smaller changes in the proportions of CA1 and granule cells. When adult neurogenesis is included, the relatively small populations of young neurons, proliferating cells and hilar neurons become main drivers of taxonomic separation within rodents. The observations provide challenges to the computational modeling of hippocampal function, suggest differences in the organization of hippocampal information streams in rodent and non

How Can Adult Children Influence Parents’ Long-Term Care Insurance Purchase Decisions?

Science.gov (United States)

Voils, Corrine I.; Coe, Norma B.; Konetzka, R. Tamara; Boles, Jillian; Van Houtven, Courtney Harold

2017-01-01

Abstract Purpose of the Study: Long-term care (LTC) poses a significant strain on public health insurance financing. In response, there is policy interest in bolstering the private long-term care insurance (LTCI) market. Although families are central to LTC provision, their role in LTCI demand remains unclear. The purpose of this study was to obtain in-depth information concerning: (a) How do older parents evaluate the need for LTCI, (b) what role do adult children play? and (c) How do families communicate about parents’ LTC preferences and plans, including LTCI purchase? Design and Methods: We conducted focus groups with older parents and adult children in diverse markets. Two groups were conducted with older parents who had purchased LTCI and two with parents who had not purchased LTCI. Four groups were conducted with adult children, mixed as to whether their parents had purchased LTCI. Probes were informed by published reasons for purchasing or not purchasing LTCI. We analyzed transcriptions using directed content analysis and constant comparative method. Results: Older parents valued autonomy for themselves and their children. Older parent purchasers regarded LTCI as supporting this value while nonpurchasers perceived limitations. Adult children described unstated expectations that they would care for their parents. Though discussions between parents and children about LTCI were rare, successful influence occurred when children appealed to shared values, specifically avoiding burden and remaining home. Implications: Messages that emphasize autonomy over LTC decisions and interventions that start the LTC conversation among families, with attention to shared values, could increase private LTCI uptake. PMID:25209446

The longitudinal relationship between the use of long-term care and depressive symptoms in older adults

NARCIS (Netherlands)

Pot, A.M.; Deeg, D.J.H.; Twisk, J.W.R.; Beekman, A.T.F.; Zarit, S.H.

2005-01-01

PURPOSE: The aim of this study was to estimate the longitudinal relationship between transitions in the use of long-term care and older adults' depressive symptoms and to investigate whether this relationship could be explained by markers of older adults' underlying health, or other variables

Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease

International Nuclear Information System (INIS)

Tang, Jun; Song, Min; Wang, Yanyan; Fan, Xiaotang; Xu, Haiwei; Bai, Yun

2009-01-01

In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP swe /PS1 ΔE9 mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP swe /PS1 ΔE9 transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

Problems identified by dual sensory impaired older adults in long-term care when using a self-management program : A qualitative study

NARCIS (Netherlands)

Roets-Merken, Lieve; Zuidema, Sytse; Vernooij-Dassen, Myrra; Dees, Marianne; Hermsen, Pieter; Kempen, Gertrudis; Graff, Maud

2017-01-01

OBJECTIVE: To gain insights into the problems of dual sensory impaired older adults in long-term care. Insights into these problems are essential for developing adequate policies which address the needs of the increasing population of dual sensory impaired older adults in long-term care. METHODS: A

Problems identified by dual sensory impaired older adults in long-term care when using a self-management program : A qualitative study

NARCIS (Netherlands)

Roets-Merken, Lieve; Zuidema, Sytse; Vernooij-Dassen, Myrra; Dees, Marianne; Hermsen, Pieter; Kempen, Gertrudis; Graff, Maud

2017-01-01

Objective To gain insights into the problems of dual sensory impaired older adults in long-term care. Insights into these problems are essential for developing adequate policies which address the needs of the increasing population of dual sensory impaired older adults in long-term care. Methods A

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.

Long-term exercise adherence after public health training in at-risk adults

DEFF Research Database (Denmark)

Riktrup Hansen Saida, Trine Gro; Juul Sørensen, Tina; Langberg, Henning

2017-01-01

and self-rated health. Predictors of long-term exercise adherence were assessed by logistic regression, estimating crude odds-ratios (OR) and 95% confidence intervals (95% CIs) and adjusting for age, gender, education, smoking, moderate and vigorous exercise. Results: In total, 214 adults (mean age 58......Objectives: Sustainment of healthy exercise behavior is essential in preventing cardiovascular disease and diabetes. Few studies have explored long-term exercise adherence after an exercise referral scheme. The objective of this study was to examine 12-month exercise adherence after an exercise...... intervention program. Methods: This was a pragmatic follow-up study in at-risk people performed between June 2012 and January 2014. The main outcome measure was self-reported single-item exercise adherence. Secondary outcomes were change in exercise level, quality of life rated on a visual analog scale...

Sex-Dependent and Independent Effects of Long-Term Voluntary Wheel Running on Bdnf mRNA and Protein Expression

OpenAIRE

Venezia, Andrew C.; Guth, Lisa M.; Sapp, Ryan M.; Spangenburg, Espen E.; Roth, Stephen M.

2016-01-01

The beneficial effects of physical activity on brain health (synaptogenesis, neurogenesis, enhanced synaptic plasticity, improved learning and memory) appear to be mediated through changes in region-specific expression of neurotrophins, transcription factors, and postsynaptic receptors, though investigations of sex differences in response to long-term voluntary wheel running are limited.

Toll-like receptor 2 promotes neurogenesis from the dentate gyrus after photothrombotic cerebral ischemia in mice.

Science.gov (United States)

Seong, Kyung-Joo; Kim, Hyeong-Jun; Cai, Bangrong; Kook, Min-Suk; Jung, Ji-Yeon; Kim, Won-Jae

2018-03-01

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

The male sex pheromone darcin stimulates hippocampal neurogenesis and cell proliferation in the subventricular zone in female mice

Directory of Open Access Journals (Sweden)

Emma eHoffman

2015-04-01

Full Text Available The integration of newly generated neurons persists throughout life in the mammalian olfactory bulb and hippocampus, regions involved in olfactory and spatial learning. Social cues can be potent stimuli for increasing adult neurogenesis; for example, odors from dominant but not subordinate male mice increase neurogenesis in both brain regions of adult females. However, little is known about the role of neurogenesis in social recognition or the assessment of potential mates. Dominant male mice scent-mark territories using urine that contains a number of pheromones including darcin (MUP20, a male-specific major urinary protein that stimulates rapid learned attraction to the spatial location and individual odor signature of the scent owner. Here we investigate whether exposure to darcin stimulates neurogenesis in the female brain. Hippocampal neurons and cellular proliferation in the lateral ventricles that supply neurons to the olfactory bulbs increased in females exposed for seven days to male urine containing at least 0.5µg/µl darcin. Darcin was effective whether presented alone or in the context of male urine, but other information in male urine appeared to modulate the proliferative response. When exposed to urine from wild male mice, hippocampal proliferation increased only if urine was from the same individual over seven days, suggesting that consistency of individual scent signatures is important. While seven days exposure to male scent initiated the first stages of increased neurogenesis, this caused no immediate increase in female attraction to the scent or in the strength or robustness of spatial learning in short-term conditioned place preference tests. The reliable and consistent stimulation of neurogenesis by a pheromone important in rapid social learning suggests that this may provide an excellent model to explore the relationship between the integration of new neurons and plasticity in spatial and olfactory learning in a socially

The Longitudinal Relationship between the Use of Long-Term Care and Depressive Symptoms in Older Adults

Science.gov (United States)

Pot, Anne Margriet; Deeg, Dorly J.H.; Twisk, Jos W.R.; Beekman, Aartjan T.F.; Zarit, Steven H.

2005-01-01

Purpose: The aim of this study was to estimate the longitudinal relationship between transitions in the use of long-term care and older adults' depressive symptoms and to investigate whether this relationship could be explained by markers of older adults' underlying health, or other variables including demographics, personality, and partner…

How Can Adult Children Influence Parents' Long-Term Care Insurance Purchase Decisions?

Science.gov (United States)

Sperber, Nina R; Voils, Corrine I; Coe, Norma B; Konetzka, R Tamara; Boles, Jillian; Van Houtven, Courtney Harold

2017-04-01

Long-term care (LTC) poses a significant strain on public health insurance financing. In response, there is policy interest in bolstering the private long-term care insurance (LTCI) market. Although families are central to LTC provision, their role in LTCI demand remains unclear. The purpose of this study was to obtain in-depth information concerning: (a) How do older parents evaluate the need for LTCI, (b) what role do adult children play? and (c) How do families communicate about parents' LTC preferences and plans, including LTCI purchase? We conducted focus groups with older parents and adult children in diverse markets. Two groups were conducted with older parents who had purchased LTCI and two with parents who had not purchased LTCI. Four groups were conducted with adult children, mixed as to whether their parents had purchased LTCI. Probes were informed by published reasons for purchasing or not purchasing LTCI. We analyzed transcriptions using directed content analysis and constant comparative method. Older parents valued autonomy for themselves and their children. Older parent purchasers regarded LTCI as supporting this value while nonpurchasers perceived limitations. Adult children described unstated expectations that they would care for their parents. Though discussions between parents and children about LTCI were rare, successful influence occurred when children appealed to shared values, specifically avoiding burden and remaining home. Messages that emphasize autonomy over LTC decisions and interventions that start the LTC conversation among families, with attention to shared values, could increase private LTCI uptake. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Putative adult neurogenesis in two domestic pigeon breeds (Columba livia domestica): racing homer versus utility carneau pigeons.

Science.gov (United States)

Mazengenya, Pedzisai; Bhagwandin, Adhil; Nkomozepi, Pilani; Manger, Paul R; Ihunwo, Amadi O

2017-07-01

Generation of neurons in the brains of adult birds has been studied extensively in the telencephalon of song birds and few studies are reported on the distribution of PCNA and DCX in the telencephalon of adult non-song learning birds. We report here on adult neurogenesis throughout the brains of two breeds of adult domestic pigeons (Columba livia domestica), the racing homer and utility carneau using endogenous immunohistochemical markers proliferating cell nuclear antigen (PCNA) for proliferating cells and doublecortin (DCX) for immature and migrating neurons. The distribution of PCNA and DCX immunoreactivity was very similar in both pigeon breeds with only a few minor differences. In both pigeons, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, walls of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and cerebellum. Generally, the olfactory bulbs and telencephalon had more PCNA and DCX cells than other regions. Two proliferative hotspots were evident in the dorsal and ventral poles of the lateral ventricles. PCNA- and DCX-immunoreactive cells migrated radially from the walls of the lateral ventricle into the parenchyma. In most telencephalic regions, the density of PCNA- and DCX-immunoreactive cells increased from rostral to caudal, except in the mesopallium where the density decreased from rostral to middle levels and then increased caudally. DCX immunoreactivity was more intense in fibres than in cell bodies and DCX-immunoreactive cells included small granular cells, fusiform bipolar cells, large round and or polygonal multipolar cells. The similarity in the distribution of proliferating cells and new neurons in the telencephalon of the two breeds of pigeons may suggest that adult neurogenesis is a conserved trait as an ecological adaptation irrespective of body size.

Putative adult neurogenesis in two domestic pigeon breeds (Columba livia domestica: racing homer versus utility carneau pigeons

Directory of Open Access Journals (Sweden)

Pedzisai Mazengenya

2017-01-01

Full Text Available Generation of neurons in the brains of adult birds has been studied extensively in the telencephalon of song birds and few studies are reported on the distribution of PCNA and DCX in the telencephalon of adult non-song learning birds. We report here on adult neurogenesis throughout the brains of two breeds of adult domestic pigeons (Columba livia domestica, the racing homer and utility carneau using endogenous immunohistochemical markers proliferating cell nuclear antigen (PCNA for proliferating cells and doublecortin (DCX for immature and migrating neurons. The distribution of PCNA and DCX immunoreactivity was very similar in both pigeon breeds with only a few minor differences. In both pigeons, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, walls of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and cerebellum. Generally, the olfactory bulbs and telencephalon had more PCNA and DCX cells than other regions. Two proliferative hotspots were evident in the dorsal and ventral poles of the lateral ventricles. PCNA- and DCX-immunoreactive cells migrated radially from the walls of the lateral ventricle into the parenchyma. In most telencephalic regions, the density of PCNA- and DCX-immunoreactive cells increased from rostral to caudal, except in the mesopallium where the density decreased from rostral to middle levels and then increased caudally. DCX immunoreactivity was more intense in fibres than in cell bodies and DCX-immunoreactive cells included small granular cells, fusiform bipolar cells, large round and or polygonal multipolar cells. The similarity in the distribution of proliferating cells and new neurons in the telencephalon of the two breeds of pigeons may suggest that adult neurogenesis is a conserved trait as an ecological adaptation irrespective of body size.

Long-Term Visual Training Increases Visual Acuity and Long-Term Monocular Deprivation Promotes Ocular Dominance Plasticity in Adult Standard Cage-Raised Mice

OpenAIRE

Hosang, Leon; Yusifov, Rashad; Löwel, Siegrid

2018-01-01

Abstract For routine behavioral tasks, mice predominantly rely on olfactory cues and tactile information. In contrast, their visual capabilities appear rather restricted, raising the question whether they can improve if vision gets more behaviorally relevant. We therefore performed long-term training using the visual water task (VWT): adult standard cage (SC)-raised mice were trained to swim toward a rewarded grating stimulus so that using visual information avoided excessive swimming toward ...

Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

Directory of Open Access Journals (Sweden)

Bruno P. Carreira

2015-01-01

Full Text Available Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO. In these conditions, NO promotes proliferation of neural stem cells (NSC in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.

Long-lasting memory deficits in mice withdrawn from cocaine are concomitant with neuroadaptations in hippocampal basal activity, GABAergic interneurons and adult neurogenesis

Directory of Open Access Journals (Sweden)

David Ladrón de Guevara-Miranda

2017-03-01

Full Text Available Cocaine addiction disorder is notably aggravated by concomitant cognitive and emotional pathology that impedes recovery. We studied whether a persistent cognitive/emotional dysregulation in mice withdrawn from cocaine holds a neurobiological correlate within the hippocampus, a limbic region with a key role in anxiety and memory but that has been scarcely investigated in cocaine addiction research. Mice were submitted to a chronic cocaine (20 mg/kg/day for 12 days or vehicle treatment followed by 44 drug-free days. Some mice were then assessed on a battery of emotional (elevated plus-maze, light/dark box, open field, forced swimming and cognitive (object and place recognition memory, cocaine-induced conditioned place preference, continuous spontaneous alternation behavioral tests, while other mice remained in their home cage. Relevant hippocampal features [basal c-Fos activity, GABA+, parvalbumin (PV+ and neuropeptide Y (NPY+ interneurons and adult neurogenesis (cell proliferation and immature neurons] were immunohistochemically assessed 73 days after the chronic cocaine or vehicle protocol. The cocaine-withdrawn mice showed no remarkable exploratory or emotional alterations but were consistently impaired in all the cognitive tasks. All the cocaine-withdrawn groups, independent of whether they were submitted to behavioral assessment or not, showed enhanced basal c-Fos expression and an increased number of GABA+ cells in the dentate gyrus. Moreover, the cocaine-withdrawn mice previously submitted to behavioral training displayed a blunted experience-dependent regulation of PV+ and NPY+ neurons in the dentate gyrus, and neurogenesis in the hippocampus. Results highlight the importance of hippocampal neuroplasticity for the ingrained cognitive deficits present during chronic cocaine withdrawal.

Long term effects of parenting and family characteristics on delinquency of male young adults

NARCIS (Netherlands)

Hoeve, M.; Smeenk, W.; Loeber, R.; Southamer-Loeber, M.; van der Laan, P.H.; Gerris, J.R.; Dubas, J.S.

2007-01-01

Drawing from the criminology literature and family studies, we investigated the long-term effects of established family risk factors and parenting styles on male young adult delinquency. We used data sets from two longitudinal studies, the Pittsburgh Youth Study (N474) and the Child-Rearing and

Long-Term Outcomes of Cultivated Limbal Epithelial Transplantation: Evaluation and Comparison of Results in Children and Adults

Directory of Open Access Journals (Sweden)

Anita Ganger

2015-01-01

Full Text Available Purpose. To compare the long-term clinical outcomes of cultivated limbal epithelial transplantation (CLET in children and adults with limbal stem cell deficiency. Design. Retrospective case series. Methods. Case records of patients with limbal stem cell deficiency (LSCD who underwent CLET from April 2004 to December 2014 were studied. Outcome measures were compared in terms of anatomical success and visual improvement. Parameters for total anatomical success were avascular, epithelized, and clinically stable corneal surface without conjunctivalization, whereas partial anatomical success was considered when mild vascularization (sparing centre of cornea and mild conjunctivalization were noted along with complete epithelization. Results. A total of 62 cases underwent the CLET procedure: 38 (61.3% were children and 24 (38.7% were adults. Patients with unilateral LSCD (33 children and 21 adults had autografts and those with bilateral LSCD (5 children and 3 adults had allografts. Amongst the 54 autografts partial and total anatomical success were noted in 21.2% and 66.6% children, respectively, and 19.0% and 80.9% in adults, respectively (p value 0.23. Visual improvement of 1 line and ≥2 lines was seen in 57.5% and 21.2% children, respectively, and 38% and 38% in adults, respectively (p value 0.31. Conclusion. Cultivated limbal epithelial transplantation gives good long-term results in patients with LSCD and the outcomes are comparable in children and adults.

Neuronal Rac1 Is Required for Learning-Evoked Neurogenesis

Science.gov (United States)

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

2013-01-01

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

Omega-3 fatty acids upregulate adult neurogenesis

OpenAIRE

Beltz, Barbara S.; Tlusty, Michael F.; Benton, Jeannie L.; Sandeman, David C.

2007-01-01

Omega-3 fatty acids play crucial roles in the development and function of the central nervous system. These components, which must be obtained from dietary sources, have been implicated in a variety of neurodevelopmental and psychiatric disorders. Furthermore, the presence of omega-6 fatty acids may interfere with omega-3 fatty acid metabolism. The present study investigated whether changes in dietary ratios of omega-3:omega-6 fatty acids influence neurogenesis in the lobster (Homarus america...

Long-term outcomes for adult craniopharyngioma following radiation therapy

International Nuclear Information System (INIS)

Masson-Cote, Laurence; Masucci, Giuseppina Laura; Millar, Barbara-Ann; Laperriere, Normand J.; Atenafu, Eshetu G.; Cusimano, Michael; Croul, Sidney; Mason, Warren; Sahgal, Arjun; Dept. of Radiation Oncology, Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto

2013-01-01

Background. We report long-term outcomes in adult patients with craniopharyngioma following surgery and radiation therapy (RT). Material and methods. Fifty-three patients treated with RT (median, 50 Gy in 25 fractions) between 1980 and 2009 with pathologically confirmed craniopharyngioma were reviewed (53% solid and 47% cystic/solid). The median age was 53 years (range, 22-76), 53% were female, 83% were sub-totally resected, 6% were gross totally resected and 11% had a biopsy and/or cyst aspiration alone. RT was delivered adjuvantly in 53% of patients as opposed to salvage intent upon progression. Results. Median follow-up was seven years (86 months, range, 8-259). The 5- and 10-year progression-free survival (PFS) rates were 85% and 69%, overall survival (OS) rates were 76% and 70%, and cause-specific survival (CSS) rates were both 88%, respectively. Both univariable and multivariable analysis identified age ( 2 surgeries prior to RT (p =0.01). Neither the intent of radiation or tumor type (cystic vs. solid/cystic) were prognostic or predictive. New endocrinopathies and visual dysfunction were observed in 53% and 17% of patients post-surgery, and in 11% and 6% post-RT, respectively. Conclusion. We report long-term favorable PFS, CSS and OS for craniopharyngioma post-RT. We observe age as a significant prognostic factor, however, timing of radiation was not

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

Science.gov (United States)

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

2012-11-01

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

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

Science.gov (United States)

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

2013-12-01

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

Neurogenesis in the aging brain.

Science.gov (United States)

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

2017-10-01

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

Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD.

Science.gov (United States)

Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsoyr, Ole; Faraone, Stephen V; Peleikis, Dawn E

2014-06-01

Few studies have examined the impact of childhood attention deficit hyperactivity disorder (ADHD) symptoms on adult ADHD functional outcomes. To address this issue dimensionally, ADHD symptoms in childhood and adulthood and their relation to educational deficits and work disability are studied in a clinical sample of adult patients with previously untreated ADHD. About 250 adults diagnosed systematically with ADHD according to DSM-IV were prospectively recruited. Primary outcomes were high school dropout and being out of the work last year. Childhood ADHD symptoms, sex differences, comorbidities of other mental disorders, and adult ADHD symptoms were examined by historical data, clinician interviews, and questionnaires. High levels of ADHD symptom severity in childhood were related to dropping out of high school [odds ratio (OR) = 3.0], as were higher numbers of hyperactive-impulsive symptoms in childhood. Significantly, more women than men were long-term work disabled (OR = 2.0). After adjusting for age and gender, persisting high levels of ADHD inattention symptoms in adulthood (OR = 2.5), number of comorbid disorders, and particularly anxiety disorders were significantly related to long-term work disability. Childhood hyperactive-impulsive symptoms and overall severity of childhood ADHD symptoms were associated with high school dropout rates; however, persisting ADHD inattention symptoms and comorbid mental disorders in adulthood were more correlated to occupational impairment. These findings underline proposals for studies on early recognition and interventions for ADHD and psychiatric comorbidity. They further suggest that inattentive symptoms be a focus of adult ADHD treatment and that workplace interventions be considered to prevent long-term work disability.

The Long-Term Effects of Parental Divorce on the Mental Health of Young Adults: A Developmental Perspective.

Science.gov (United States)

Chase-Lansdale, P. Lindsay; And Others

1995-01-01

Examined effects on young adults (23 years) of parental divorce during childhood and adolescence using data from Britain's longitudinal National Child Development study. Found that divorce had a moderate, long-term negative impact on young adults' mental health; the relative risk of serious emotional disorders increased in the aftermath of…

Long-term outcomes for adult craniopharyngioma following radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Masson-Cote, Laurence; Masucci, Giuseppina Laura; Millar, Barbara-Ann; Laperriere, Normand J. [Dept. of Radiation Oncology, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Atenafu, Eshetu G. [Dept. of Biostatistics, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Cusimano, Michael [Dept. of Surgery, Div. of Neurosurgery, St. Michaels Hospital, Toronto (Canada); Croul, Sidney [Dept. of Pathology, Univ. of Toronto, Toronto (Canada); Mason, Warren [Dept. of Medicine, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Sahgal, Arjun [Dept. of Radiation Oncology, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada), E-mail: Arjun.sahgal@rmp.uhn.on.ca; Dept. of Radiation Oncology, Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto (Canada)

2013-01-15

Background. We report long-term outcomes in adult patients with craniopharyngioma following surgery and radiation therapy (RT). Material and methods. Fifty-three patients treated with RT (median, 50 Gy in 25 fractions) between 1980 and 2009 with pathologically confirmed craniopharyngioma were reviewed (53% solid and 47% cystic/solid). The median age was 53 years (range, 22-76), 53% were female, 83% were sub-totally resected, 6% were gross totally resected and 11% had a biopsy and/or cyst aspiration alone. RT was delivered adjuvantly in 53% of patients as opposed to salvage intent upon progression. Results. Median follow-up was seven years (86 months, range, 8-259). The 5- and 10-year progression-free survival (PFS) rates were 85% and 69%, overall survival (OS) rates were 76% and 70%, and cause-specific survival (CSS) rates were both 88%, respectively. Both univariable and multivariable analysis identified age (<53 or {>=}53) as a prognostic factor for OS (p =0.0003) and CSS (p =0.05). PFS was observed to be worse in patients with >2 surgeries prior to RT (p =0.01). Neither the intent of radiation or tumor type (cystic vs. solid/cystic) were prognostic or predictive. New endocrinopathies and visual dysfunction were observed in 53% and 17% of patients post-surgery, and in 11% and 6% post-RT, respectively. Conclusion. We report long-term favorable PFS, CSS and OS for craniopharyngioma post-RT. We observe age as a significant prognostic factor, however, timing of radiation was not.

Long-Term Follow-Up of Percutaneous Balloon Angioplasty in Adult Aortic Coarctation

International Nuclear Information System (INIS)

Paddon, Alex J.; Nicholson, Anthony A.; Ettles, Duncan F.; Travis, Simon J.; Dyet, John F.

2000-01-01

Purpose: To assess long-term outcomes following percutaneous transluminal angioplasty (PTA) of congenital aortic coarctation in adults.Methods: Seventeen patients underwent PTA for symptomatic adult coarctation of the aorta. Sixteen patients, with a mean age of 28 years (range 15-60 years), were reviewed at a mean interval after angioplasty of 7.3 years (range 1.5-11 years). Assessment included magnetic resonance imaging (MRI), Doppler echocardiography, and clinical examination. Current clinical measurements were compared with pre- and immediate post-angioplasty measurements.Results: At follow-up 16 patients were alive and well. The patient not included in follow-up had undergone surgical repair and excision of the coarctation segment following PTA. Mean brachial systolic blood pressure for the group decreased from 174 mmHg before angioplasty to 130 mmHg at follow-up (p 0.0001). The mean gradient had fallen significantly from 50.9 to 17.8 at follow-up (p = 0.001). The average number of antihypertensive drugs required per patient decreased from 0.56 to 0.31 (p = 0.234). No significant residual stenoses or restenoses were seen at MRI. Small but clinically insignificant residual pressure gradients were recorded in all patients using Doppler echocardiography. Complications included one transient ischemic attack at 5 days, one external iliac dissection requiring stent insertion, and a further patient who developed a false aneurysm close to the coarctation site at 12 months which subsequently required surgical excision.Conclusion: PTA of adult coarctation is safe and effective in the long term. Although primary stenting has recently been advocated in the treatment of this condition, our results suggest that PTA remains the treatment of choice

Final adult height in long-term growth hormone-treated achondroplasia patients.

Science.gov (United States)

Harada, Daisuke; Namba, Noriyuki; Hanioka, Yuki; Ueyama, Kaoru; Sakamoto, Natsuko; Nakano, Yukako; Izui, Masafumi; Nagamatsu, Yuiko; Kashiwagi, Hiroko; Yamamuro, Miho; Ishiura, Yoshihito; Ogitani, Ayako; Seino, Yoshiki

2017-07-01

The objective of this study was to evaluate the gain in final height of achondroplasia (ACH) patients with long-term growth hormone (GH) treatment. We analyzed medical data of 22 adult patients (8 males and 14 females) treated with GH at a dose of 0.05 mg/kg/day. Optionally, tibial lengthening (TL) was performed with the Ilizalov method in 15 patients and TL as well as femoral lengthening (FL) in 6 patients. Concomitant gonadal suppression therapy with buserelin acetate was applied in 13 patients. The mean treatment periods with GH were 10.7 ± 4.0 and 9.3 ± 2.5 years for males and females, respectively. GH treatment augmented the final height +0.60 ± 0.52 SD (+3.5 cm) and +0.51 ± 1.29 SD (+2.8 cm) in males and females compared to non-treated ACH patients, respectively. Final height of ACH patients that underwent GH and TL increased +1.72 ± 0.72 SD (+10.0 cm) and +1.95 ± 1.34 SD (+9.8 cm) in males and females, respectively. GH, TL, and FL increased their final height +2.97 SD (+17.2 cm) and +3.41 ± 1.63 SD (+17.3 cm) in males and females, respectively. Gonadal suppression therapy had no impact on final height. Long-term GH treatment contributes to 2.6 and 2.1% of final adult height in male and female ACH patients, respectively.

Adolescent but not adult-born neurons are critical for susceptibility to chronic social defeat

Directory of Open Access Journals (Sweden)

Greer S Kirshenbaum

2014-08-01

Full Text Available Recent evidence implicates adult hippocampal neurogenesis in regulating behavioral and physiologic responses to stress. Hippocampal neurogenesis occurs across the lifespan, however the rate of cell birth is up to 300% higher in adolescent mice compared to adults. Adolescence is a sensitive period in development where emotional circuitry and stress reactivity undergo plasticity establishing life-long set points. Therefore neurogenesis occurring during adolescence may be particularly important for emotional behavior. However, little is known about the function of hippocampal neurons born during adolescence. In order to assess the contribution of neurons born in adolescence to the adult stress response and depression-related behavior, we transiently reduced cell proliferation either during adolescence, or during adulthood in GFAP-Tk mice. We found that the intervention in adolescence did not change baseline behavioral responses in the forced swim test, sucrose preference test or social affiliation test, and did not change corticosterone responses to an acute stressor. However following chronic social defeat, adult mice with reduced adolescent neurogenesis showed a resilient phenotype. A similar transient reduction in adult neurogenesis did not affect depression-like behaviors or stress induced corticosterone. Our study demonstrates that hippocampal neurons born during adolescence, but not in adulthood are important to confer susceptibility to chronic social defeat.

Sexuality and physical intimacy in long-term care.

Science.gov (United States)

Lichtenberg, Peter A

2014-01-01

Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long-term care settings. Because older adults in medical rehabilitation and long-term care beds present with significant frailties, and often significant neurocognitive disorders, it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literature on sexuality and aging, examines some of the clinical practices and guidelines regarding sexual expression in long-term care, and presents two case examples. A semistructured interview and decision tree is presented to assist therapists in making careful and informed decisions and thereby balancing the needs for protection with the needs for autonomy.

Long-term culture of undifferentiated spermatogonia isolated from immature and adult bovine testes.

Science.gov (United States)

Suyatno; Kitamura, Yuka; Ikeda, Shuntaro; Minami, Naojiro; Yamada, Masayasu; Imai, Hiroshi

2018-03-01

Undifferentiated spermatogonia eventually differentiate in the testis to produce haploid sperm. Within this cell population, there is a small number of spermatogonial stem cells (SSCs). SSCs are rare cells in the testis, and their cellular characteristics are poorly understood. Establishment of undifferentiated cell line would provide an indispensable tool for studying their biological nature and spermiogenesis/spermatogenesis in vitro. However, there have been few reports on the long-term culture of undifferentiated spermatogonia in species other than rodents. Here, we report the derivation and long-term in vitro culture of undifferentiated spermatogonia cell lines from immature and adult bovine testes. Cell lines from immature testes were maintained in serum-free culture conditions in the presence of glial-cell-line-derived neurotropic factor (GDNF) and bovine leukemia inhibitory factor (bLIF). These cell lines have embryonic stem (ES)-like cell morphology, express pluripotent-stem-cell-specific and germ-cell-specific markers at the protein and mRNA levels, and contributed to the inner cell mass (ICM) of embryos in the blastocyst stage. Meanwhile, cell lines established from adult testes were maintained in low-serum media in the presence of 6-bromoindirubin-3'-oxime (BIO). These cell lines have characteristics resembling those of previously reported male mouse germ cell lines as confirmed by their botryoidally aggregated morphology, as well as the expression of germ-cell-specific markers and pluripotent stem cell markers. These findings could be useful for the development of long-term culture of undifferentiated spermatogonia, which could aid in conservation of species and improvement of livestock production through genome editing technology. © 2018 Wiley Periodicals, Inc.

Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus.

Directory of Open Access Journals (Sweden)

James C Walton

Full Text Available Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD and short day lengths (SD for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus.

Hippocampal neurogenesis and cortical cellular plasticity in Wahlberg's epauletted fruit bat: a qualitative and quantitative study.

Science.gov (United States)

Gatome, Catherine W; Mwangi, Deter K; Lipp, Hans-Peter; Amrein, Irmgard

2010-01-01

Species-specific characteristics of neuronal plasticity emerging from comparative studies can address the functional relevance of hippocampal or cortical plasticity in the light of ecological adaptation and evolutionary history of a given species. Here, we present a quantitative and qualitative analysis of neurogenesis in young and adult free-living Wahlberg's epauletted fruit bats. Using the markers for proliferating cell nuclear antigen (PCNA), bromodeoxyuridine (BrdU), doublecortin (DCX) and polysialic acid neural cell adhesion molecule (PSA-NCAM), our findings in the hippocampus, olfactory bulb and cortical regions are described and compared to reports in other mammals. Expressed as a percentage of the total number of granule cells, PCNA- and BrdU-positive cells accounted for 0.04 in young to 0.01% in adult animals; DCX-positive cells for 0.05 (young) to 0.01% (adult); PSA-NCAM-positive cells for 0.1 (young) to 0.02% (adult), and pyknotic cells for 0.007 (young) to 0.005% (adult). The numbers were comparable to other long-lived, late-maturing mammals such as primates. A significant increase in the total granule cell number from young to adult animals demonstrated the successful formation and integration of new cells. In adulthood, granule cell number appeared stable and was surprisingly low in comparison to other species. Observations in the olfactory bulb and rostral migratory stream were qualitatively similar to descriptions in other species. In the ventral horn of the lateral ventricle, we noted prominent expression of DCX and PSA-NCAM forming a temporal migratory stream targeting the piriform cortex, possibly reflecting the importance of olfaction to these species. Low, but persistent hippocampal neurogenesis in non-echolocating fruit bats contrasted the findings in echolocating microbats, in which hippocampal neurogenesis was largely absent. Together with the observed intense cortical plasticity in the olfactory system of fruit bats we suggest a

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

Science.gov (United States)

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

2017-08-20

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

Making Music, Making Friends: Long-Term Music Therapy with Young Adults with Severe Learning Disabilities

Science.gov (United States)

Pavlicevic, Mercédès; O'Neil, Nicky; Powell, Harriet; Jones, Oonagh; Sampathianaki, Ergina

2014-01-01

This collaborative practitioner research study emerged from music therapists' concerns about the value of improvisational, music-centred music therapy for young adults with severe learning disabilities (SLDs), given the long-term nature of such work. Concerns included the relevance, in this context, of formulating, and reporting on, therapeutic…

Cellular and Behavioral Effects of Cranial Irradiation of the Subventricular Zone in Adult Mice

Science.gov (United States)

Lazarini, Françoise; Mouthon, Marc-André; Gheusi, Gilles; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lamarque, Stéphanie; Abrous, Djoher Nora; Boussin, François D.; Lledo, Pierre-Marie

2009-01-01

Background In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear. Methodology/Principal Findings In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation. Conclusion/Significance These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces. PMID:19753118

Cellular and behavioral effects of cranial irradiation of the subventricular zone in adult mice.

Directory of Open Access Journals (Sweden)

Françoise Lazarini

2009-09-01

Full Text Available In mammals, new neurons are added to the olfactory bulb (OB throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear.In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation.These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces.

Persistent changes in ability to express long-term potentiation/depression in the rat hippocampus after juvenile/adult stress.

Science.gov (United States)

Maggio, Nicola; Segal, Menahem

2011-04-15

The ventral hippocampus (VH) was recently shown to express lower magnitude long-term potentiation (LTP) compared with the dorsal hippocampus (DH). Exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than that produced in the DH, which was reduced by stress. Stressful experience in adolescence has been shown to produce long-lasting effects on animal behavior and on ability to express LTP/long-term depression (LTD) of reactivity to afferent stimulation in the adult. We are interested in possible interactions between juvenile and adult stress in their effects of adult plasticity. We studied the effects of a composite juvenile (28-30 days) stress, followed by a reminder stressful experience in the young adult (60 days) rat, on the ability to produce LTP and LTD in CA1 region of slices of the VH and DH. Juvenile or adult stress produced a transient decrease in ability to express LTP in DH and a parallel increase in LTP in VH. Stress in the young adult after juvenile stress produced a striking prolongation of the DH/VH disparity with respect to the ability to express both LTP and LTD into the adulthood of the rat. These results have important implications for the impact of juvenile stress on adult neuronal plasticity and on the understanding the functions of the different sectors of the hippocampus. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis.

Science.gov (United States)

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

2012-08-01

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

Long-Term Treatment with Paroxetine Increases Verbal Declarative Memory and Hippocampal Volume in Posttraumatic Stress Disorder

Science.gov (United States)

Vermetten, Eric; Vythilingam, Meena; Southwick, Steven M.; Charney, Dennis S.; Bremner, J. Douglas

2011-01-01

Background Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. Methods Declarative memory was assessed with the Wechsler Memory Scale–Revised and Selective Reminding Test before and after 9–12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. Results Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. Conclusions These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD. PMID:14512209

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

Science.gov (United States)

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

2018-05-01

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

Using High Performance Computing to Examine the Processes of Neurogenesis Underlying Pattern Separation and Completion of Episodic Information.

Energy Technology Data Exchange (ETDEWEB)

Aimone, James Bradley; Bernard, Michael Lewis; Vineyard, Craig Michael; Verzi, Stephen Joseph.

2014-10-01

Adult neurogenesis in the hippocampus region of the brain is a neurobiological process that is believed to contribute to the brain's advanced abilities in complex pattern recognition and cognition. Here, we describe how realistic scale simulations of the neurogenesis process can offer both a unique perspective on the biological relevance of this process and confer computational insights that are suggestive of novel machine learning techniques. First, supercomputer based scaling studies of the neurogenesis process demonstrate how a small fraction of adult-born neurons have a uniquely larger impact in biologically realistic scaled networks. Second, we describe a novel technical approach by which the information content of ensembles of neurons can be estimated. Finally, we illustrate several examples of broader algorithmic impact of neurogenesis, including both extending existing machine learning approaches and novel approaches for intelligent sensing.

The Experiences of Long-Term Unemployed Young Adults in the South West of England: Some New Insights

Science.gov (United States)

Lawy, Robert; Wheeler, Rachel

2013-01-01

In this paper we explore the experiences of three long-term unemployed young adults from different backgrounds in the 18-24 age range. The data comprise three interviews conducted over an 18-month period with seven of the original 19 participants in the research. At the time of first interview none of the young adults had been in education,…

Aromatherapy hand massage for older adults with chronic pain living in long-term care.

Science.gov (United States)

Cino, Kathleen

2014-12-01

Older adults living in long-term care experience high rates of chronic pain. Concerns with pharmacologic management have spurred alternative approaches. The purpose of this study was to examine a nursing intervention for older adults with chronic pain. This prospective, randomized control trial compared the effect of aromatherapy M technique hand massage, M technique without aromatherapy, and nurse presence on chronic pain. Chronic pain was measured with the Geriatric Multidimensional Pain and Illness Inventory factors, pain and suffering, life interference, and emotional distress and the Iowa Pain Thermometer, a pain intensity scale. Three groups of 39 to 40 participants recruited from seven long-term care facilities participated twice weekly for 4 weeks. Analysis included multivariate analysis of variance and analysis of variance. Participants experienced decreased levels of chronic pain intensity. Group membership had a significant effect on the Geriatric Multidimensional Pain Inventory Pain and Suffering scores; Iowa Pain Thermometer scores differed significantly within groups. M technique hand massage with or without aromatherapy significantly decreased chronic pain intensity compared to nurse presence visits. M technique hand massage is a safe, simple, but effective intervention. Caregivers using it could improve chronic pain management in this population. © The Author(s) 2014.

Long-term patterns of dental attendance and caries experience among British adults: a retrospective analysis.

Science.gov (United States)

Aldossary, Arwa; Harrison, Victoria E; Bernabé, Eduardo

2015-02-01

There is inconclusive evidence on the value of regular dental attendance. This study explored the relationship between long-term patterns of dental attendance and caries experience. We used retrospective data from 3,235 adults, ≥ 16 yrs of age, who participated in the Adult Dental Health Survey in the UK. Participants were classified into four groups (always, current, former, and never regular-attenders) based on their responses to three questions on lifetime dental-attendance patterns. The association between dental-attendance patterns and caries experience, as measured using the decayed, missing, or filled teeth (DMFT) index, was tested in negative binomial regression models, adjusting for demographic (sex, age, and country of residence) and socio-economic (educational attainment, household income, and social class) factors. A consistent pattern of association between long-term dental attendance and caries experience was found in adjusted models. Former and never regular-attenders had a significantly higher DMFT score and numbers of decayed and missing teeth, but fewer filled teeth, than always regular-attenders. No differences in DMFT or its components were found between current and always regular-attenders. The findings of this study show that adults with different lifetime trajectories of dental attendance had different dental statuses. © 2014 Eur J Oral Sci.

Defensive behaviors and prosencephalic neurogenesis in pigeons (Columba livia) are affected by environmental enrichment in adulthood.

Science.gov (United States)

Melleu, F F; Pinheiro, M V; Lino-de-Oliveira, C; Marino-Neto, J

2016-05-01

Neurogenesis in the adult brain appears to be phylogenetically conserved across the animal kingdom. In pigeons and other adult non-oscine birds, immature neurons are observed in several prosencephalic areas, suggesting that neurogenesis may participate in the control of different behaviors. The mechanisms controlling neurogenesis and its relevance to defensive behaviors in non-oscine birds remain elusive. Herein, the contribution of the environment to behavior and neurogenesis of pigeons was investigated. Adult pigeons (Columba livia, n = 6/group), housed in standard (SE) or enriched environment (EE) for 42 days, were exposed to an unfamiliar environment (UE) followed by presentation to a novel object (NO). Video recordings of UE+NO tests were analyzed and scored for latency, duration and frequency of angular head movements, peeping, grooming, immobility and locomotion. Twenty-four hours later, pigeons were submitted to the tonic immobility test (TI) and number of trials for TI and TI duration were scored, followed by euthanasia 2 h later. Brains were immunohistochemically processed to reveal doublecortin (DCX), a marker for newborn neurons. Compared to those housed in SE, the pigeons housed in EE responded to a NO with more immobility. In addition, the pigeons housed in EE presented longer TI, more DCX-immunoreactive (DCX-ir) cells in the hippocampus and fewer DCX-ir cells in the lateral striatum than those housed in SE. There was no correlation between the number of DCX-ir cells and the scores of immobility in behavioral tests. Together, these data suggest that enrichment favored behavioral inhibition and neurogenesis in the adult pigeons through different, parallel mechanisms.

Long-term effects of 239Pu injection in adult, weanling, newborn and fetal rats

International Nuclear Information System (INIS)

Sikov, M.R.; Mahlum, D.D.; Hess, J.O.; Carr, D.B.

1979-01-01

We have completed biological evaluations comparing long-term effects in rats exposed to 239 Pu citrate as adults, weanlings, newborns, or late fetuses, and statistical analyses have been initiated. In rats exposed postnatally, statistically significant alterations in terminal body weight and in weights of several organs were found at higher doses. Survivorship decreased with increasing dose in the postnatal groups, but not in rats exposed prenatally

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

OpenAIRE

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

2017-01-01

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

Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models.

Directory of Open Access Journals (Sweden)

Juan Jose Ramos-Rodriguez

Full Text Available Type 2 diabetes (T2D is an important risk factor to suffer dementia, including Alzheimer's disease (AD, and some neuropathological features observed in dementia could be mediated by T2D metabolic alterations. Since brain atrophy and impaired neurogenesis have been observed both T2D and AD we analyzed central nervous system (CNS morphological alterations in the db/db mice (leptin receptor KO mice, as a model of long-term insulin resistance and T2D, and in C57Bl6 mice fed with high fat diet (HFD, as a model of diet induced insulin resistance and prediabetes. Db/db mice showed an age-dependent cortical and hippocampal atrophy, whereas in HFD mice cortex and hippocampus were preserved. We also detected increased neurogenesis and cell proliferation rates in young db/db mice when compared with control littermates. Our study shows that metabolic parameters serve as predictors of both atrophy and altered proliferation and neurogenesis in the CNS. Moreover in the cortex, atrophy, cell proliferation and neurogenesis were significantly correlated. Our data suggest that T2D may underline some of the pathological features observed in the dementia process. They also support that blood glucose control in elderly patients could help to slow down dementia evolution and maybe, improve its prognosis.

Policies for replacing long-term indwelling urinary catheters in adults.

Science.gov (United States)

Cooper, Fergus P M; Alexander, Cameron Edwin; Sinha, Sanjay; Omar, Muhammad Imran

2016-07-26

Long-term indwelling catheters are used commonly in people with lower urinary tract problems in home, hospital and specialised health-care settings. There are many potential complications and adverse effects associated with long-term catheter use. The effect of health-care policies related to the replacement of long-term urinary catheters on patient outcomes is unclear. To determine the effectiveness of different policies for replacing long-term indwelling urinary catheters in adults. We searched the Cochrane Incontinence Specialised Trials Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 19 May 2016), and the reference lists of relevant articles. All randomised controlled trials investigating policies for replacing long-term indwelling urinary catheters in adults were included. At least two review authors independently performed data extraction and assessed risk of bias of all the included trials. Quality of evidence was assessed by adopting the GRADE approach. Any discrepancies were resolved by discussion between the review authors or an independent arbitrator. We contacted the authors of included trials to seek clarification where required. Three trials met the inclusion criteria, with a total of 107 participants in three different health-care settings: A USA veterans administration nursing home; a geriatric centre in Israel; and a community nursing service in Hong Kong. Data were available for three of the pre-stated comparisons. Priefer and colleagues evaluated different time intervals between catheter replacement (n = 17); Firestein and colleagues evaluated the use of antibiotic prophylaxis at the time of replacement (n = 70); and Cheung and colleagues compared two different types of cleaning solutions (n = 20).All the included trials were

Effects of Scopolamine and Melatonin Cotreatment on Cognition, Neuronal Damage, and Neurogenesis in the Mouse Dentate Gyrus.

Science.gov (United States)

Chen, Bai Hui; Ahn, Ji Hyeon; Park, Joon Ha; Choi, Soo Young; Lee, Yun Lyul; Kang, Il Jun; Hwang, In Koo; Lee, Tae-Kyeong; Shin, Bich-Na; Lee, Jae-Chul; Hong, Seongkweon; Jeon, Yong Hwan; Shin, Myoung Cheol; Cho, Jun Hwi; Won, Moo-Ho; Lee, Young Joo

2018-03-01

It has been demonstrated that melatonin plays important roles in memory improvement and promotes neurogenesis in experimental animals. We examined effects of melatonin on cognitive deficits, neuronal damage, cell proliferation, neuroblast differentiation and neuronal maturation in the mouse dentate gyrus after cotreatment of scopolamine (anticholinergic agent) and melatonin. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were intraperitoneally injected for 2 and/or 4 weeks to 8-week-old mice. Scopolamine treatment induced significant cognitive deficits 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly improved spatial learning and short-term memory impairments. Two and 4 weeks after scopolamine treatment, neurons were not damaged/dead in the dentate gyrus, in addition, no neuronal damage/death was shown after cotreatment of scopolamine and melatonin. Ki67 (a marker for cell proliferation)- and doublecortin (a marker for neuroblast differentiation)-positive cells were significantly decreased in the dentate gyrus 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly increased Ki67- and doublecortin-positive cells compared with scopolamine-treated group. However, double immunofluorescence for NeuN/BrdU, which indicates newly-generated mature neurons, did not show double-labeled cells (adult neurogenesis) in the dentate gyrus 2 and 4 weeks after cotreatment of scopolamine and melatonin. Our results suggest that melatonin treatment recovers scopolamine-induced spatial learning and short-term memory impairments and restores or increases scopolamine-induced decrease of cell proliferation and neuroblast differentiation, but does not lead to adult neurogenesis (maturation of neurons) in the mouse dentate gyrus following scopolamine treatment.

Loss of long-term depression in the insular cortex after tail amputation in adult mice.

Science.gov (United States)

Liu, Ming-Gang; Zhuo, Min

2014-01-08

The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain.

Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP{sub swe}/PS1{sub {Delta}E9} transgenic mouse model of Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Tang, Jun [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Song, Min; Wang, Yanyan [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Fan, Xiaotang [Department of Histology and Embryology, Third Military Medical University, Chongqing 400038 (China); Xu, Haiwei, E-mail: haiweixu2001@yahoo.com.cn [Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Bai, Yun, E-mail: baiyungene@gmail.com [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China)

2009-07-31

In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP{sub swe}/PS1{sub {Delta}E9} mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP{sub swe}/PS1{sub {Delta}E9} transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

Evaluation of a C57BL/6J × 129S1/SvImJ Hybrid Nestin-Thymidine Kinase Transgenic Mouse Model for Studying the Functional Significance of Exercise-Induced Adult Hippocampal Neurogenesis.

Science.gov (United States)

Hamilton, G F; Majdak, P; Miller, D S; Bucko, P J; Merritt, J R; Krebs, C P; Rhodes, J S

2015-01-01

New neurons are continuously generated in the adult hippocampus but their function remains a mystery. The nestin thymidine kinase (nestin-TK) transgenic method has been used for selective and conditional reduction of neurogenesis for the purpose of testing the functional significance of new neurons in learning, memory and motor performance. Here we explored the nestin-TK model on a hybrid genetic background (to increase heterozygosity, and "hybrid vigor"). Transgenic C57BL/6J (B6) were crossed with 129S1/SvImJ (129) producing hybrid offspring (F1) with the B6 half of the genome carrying a herpes simplex virus thymidine kinase (TK) transgene regulated by a modified nestin promoter. In the presence of exogenously administered valganciclovir, new neurons expressing TK undergo apoptosis. Female B6 nestin-TK mice ( n = 80) were evaluated for neurogenesis reduction as a positive control. Male and female F1 nestin-TK mice ( n = 223) were used to determine the impact of neurogenesis reduction on the Morris water maze (MWM) and rotarod. All mice received BrdU injections to label dividing cells and either valganciclovir or control chow, with or without a running wheel for 30 days. Both the F1 and B6 background displayed approximately 50% reduction in neurogenesis, a difference that did not impair learning and memory on the MWM or rotarod performance. Running enhanced neurogenesis and performance on the rotarod but not MWM suggesting the F1 background may not be suitable for studying pro-cognitive effects of exercise on MWM. Greater reduction of neurogenesis may be required to observe behavioral impacts. Alternatively, new neurons may not play a critical role in learning, or compensatory mechanisms in pre-existing neurons could have masked the deficits. Further work using these and other models for selectively reducing neurogenesis are needed to establish the functional significance of adult hippocampal neurogenesis in behavior.

The endogenous regenerative capacity of the damaged newborn brain: boosting neurogenesis with mesenchymal stem cell treatment.

Science.gov (United States)

Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; Kavelaars, Annemieke; Heijnen, Cobi J

2013-05-01

Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxia-ischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategies. The latest findings indicate that stem cells represent a novel therapeutic possibility to improve outcome in models of neonatal encephalopathy. Transplanted stem cells secrete factors that stimulate and maintain neurogenesis, thereby increasing cell proliferation, neuronal differentiation, and functional integration. Understanding the molecular and cellular mechanisms underlying neurogenesis after an insult is crucial for developing tools to enhance the neurogenic capacity of the brain. The aim of this review is to discuss the endogenous capacity of the neonatal brain to regenerate after a cerebral ischemic insult. We present an overview of the molecular and cellular mechanisms underlying endogenous regenerative processes during development as well as after a cerebral ischemic insult. Furthermore, we will consider the potential to use stem cell transplantation as a means to boost endogenous neurogenesis and restore brain function.

Quantifying Risk Factors for Long-Term Sleep Problems After Burn Injury in Young Adults.

Science.gov (United States)

Lee, Austin F; Ryan, Colleen M; Schneider, Jeffrey C; Kazis, Lewis E; Li, Nien Chen; Rose, Mary; Liang, Matthew H; Wang, Chao; Palmieri, Tina; Meyer, Walter J; Pidcock, Frank S; Reilly, Debra; Sheridan, Robert L; Tompkins, Ronald G

Restorative sleep is an important component of quality of life. Disturbances in sleep after burn injury were reported but all based on uncontrolled or nonstandardized data. The occurrence and the effect of long-term sleep problems in young adult burn survivors have not been well defined. This 5-year (2003-2008) prospective multicenter longitudinal study included adults with burn injuries ages 19 to 30 years who completed the Young Adult Burn Outcome Questionnaire (YABOQ) up to 36 months after injury. The items measured 15 patient-reported outcomes including physical, psychological, and social statuses and symptoms such as itch and pain. Scores of these 15 YABOQ outcome domains were standardized to a mean of 50 and a SD of 10 based on an age-matched nonburned reference group of young adults. Sleep quality was assessed using the item 'How satisfied are you now with your sleep,' rated by a 5-point Likert scale. Patients responding with very and somewhat dissatisfied were classified as having sleep dissatisfaction and the remaining as less or not dissatisfied. The associations between sleep dissatisfaction (yes/no) and YABOQ outcome domains were analyzed longitudinally using mixed-effect generalized linear models, adjusted for %TBSA burned, age, gender, and race. Generalized estimating equations were used to take into account correlated error resulting from repeated surveys on each patient over time. One hundred and fifty-two burn survivors participated in the YABOQ survey at baseline and during the follow-up who had at least one survey with a response to the sleep item. Among them, sleep dissatisfaction was twice as prevalent (76/152, 50%) when compared with the nonburned reference group (29/112, 26%). The likelihood of a burn survivor being dissatisfied with sleep was reduced over time after the burn injury. Sleep dissatisfaction following burns was significantly associated, in a dose-dependent manner, with increasing burn size (P = .001). Better sleep was associated

Neurogenesis-mediated forgetting minimizes proactive interference.

Science.gov (United States)

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

2016-02-26

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

Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis

Directory of Open Access Journals (Sweden)

Amanda Sierra

2014-01-01

Full Text Available Microglia cells are the major orchestrator of the brain inflammatory response. As such, they are traditionally studied in various contexts of trauma, injury, and disease, where they are well-known for regulating a wide range of physiological processes by their release of proinflammatory cytokines, reactive oxygen species, and trophic factors, among other crucial mediators. In the last few years, however, this classical view of microglia was challenged by a series of discoveries showing their active and positive contribution to normal brain functions. In light of these discoveries, surveillant microglia are now emerging as an important effector of cellular plasticity in the healthy brain, alongside astrocytes and other types of inflammatory cells. Here, we will review the roles of microglia in adult hippocampal neurogenesis and their regulation by inflammation during chronic stress, aging, and neurodegenerative diseases, with a particular emphasis on their underlying molecular mechanisms and their functional consequences for learning and memory.

CD34+ Testicular Stromal Cells Support Long-Term Expansion of Embryonic and Adult Stem and Progenitor Cells

Science.gov (United States)

Kim, Jiyeon; Seandel, Marco; Falciatori, Ilaria; Wen, Duancheng; Rafii, Shahin

2010-01-01

Stem cells reside in specialized microenvironments created by supporting stromal cells that orchestrate self-renewal and lineage-specific differentiation. However, the precise identity of the cellular and molecular pathways that support self-renewal of stem cells is not known. For example, long-term culture of prototypical stem cells, such as adult spermatogonial stem and progenitor cells (SPCs), in vitro has been impeded by the lack of an optimal stromal cell line that initiates and sustains proliferation of these cells. Indeed, current methods, including the use of mouse embryonic fibroblasts (MEFs), have not been efficient and have generally led to inconsistent results. Here, we report the establishment of a novel CD34-positive cell line, referred to as JK1, derived from mouse testicular stromal cells that not only facilitated long-term SPC culture but also allowed faithful generation of SPCs and multipotent stem cells. SPCs generated on JK1 maintained key features of germ line stem cells, including expression of PLZF, DAZL, and GCNA. Furthermore, these feeders also promoted the long-term cultivation of other types of primitive cells including multi-potent adult spermatogonial-derived stem cells, pluripotent murine embryonic stem cells, and embryonic germ cells derived from primordial germ cells. Stem cells could be passaged serially and still maintained expression of characteristic markers such as OCT4 and NANOG in vitro, as well as the ability to generate all three germ layers in vivo. These results indicate that the JK1 cell line is capable of promoting long-term culture of primitive cells. As such, this cell line allows for identification of stromal-derived factors that support long-term proliferation of various types of stem cells and constitutes a convenient alternative to other types of feeder layers. PMID:18669907

Paradox of pattern separation and adult neurogenesis: A dual role for new neurons balancing memory resolution and robustness.

Science.gov (United States)

Johnston, Stephen T; Shtrahman, Matthew; Parylak, Sarah; Gonçalves, J Tiago; Gage, Fred H

2016-03-01

Hippocampal adult neurogenesis is thought to subserve pattern separation, the process by which similar patterns of neuronal inputs are transformed into distinct neuronal representations, permitting the discrimination of highly similar stimuli in hippocampus-dependent tasks. However, the mechanism by which immature adult-born dentate granule neurons cells (abDGCs) perform this function remains unknown. Two theories of abDGC function, one by which abDGCs modulate and sparsify activity in the dentate gyrus and one by which abDGCs act as autonomous coding units, are generally suggested to be mutually exclusive. This review suggests that these two mechanisms work in tandem to dynamically regulate memory resolution while avoiding memory interference and maintaining memory robustness. Copyright © 2015 Elsevier Inc. All rights reserved.

Regenerative medicine using adult neural stem cells: the potential for diabetes therapy and other pharmaceutical applications

Institute of Scientific and Technical Information of China (English)

Tomoko Kuwabara; Makoto Asashima

2012-01-01

Neural stem cells (NSCs),which are responsible for continuous neurogenesis during the adult stage,are present in human adults.The typical neurogenic regions are the hippocampus and the subventricular zone; recent studies have revealed that NSCs also exist in the olfactory bulb.Olfactory bulb-derived neural stem cells (OB NSCs) have the potential to be used in therapeutic applications and can be easily harvested without harm to the patient.Through the combined influence of extrinsic cues and innate programming,adult neurogenesis is a finely regulated process occurring in a specialized cellular environment,a niche.Understanding the regulatory mechanisms of adult NSCs and their cellular niche is not only important to understand the physiological roles of neurogenesis in adulthood,but also to provide the knowledge necessary for developing new therapeutic applications using adult NSCs in other organs with similar regulatory environments.Diabetes is a devastating disease affecting more than 200 million people worldwide.Numerous diabetic patients suffer increased symptom severity after the onset,involving complications such as retinopathy and nephropathy.Therefore,the development of treatments for fundamental diabetes is important.The utilization of autologous cells from patients with diabetes may address challenges regarding the compatibility of donor tissues as well as provide the means to naturally and safely restore function,reducing future risks while also providing a long-term cure.Here,we review recent findings regarding the use of adult OB NSCs as a potential diabetes cure,and discuss the potential of OB NSC-based pharmaceutical applications for neuronal diseases and mental disorders.

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

Directory of Open Access Journals (Sweden)

Anna Fiorentini

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

A fall prevention guideline for older adults living in long-term care facilities.

Science.gov (United States)

Jung, D; Shin, S; Kim, H

2014-12-01

Falls are among the most frequent critical health problems for older adults over 65 years of age and often result in consequential injuries. This study developed a guideline covering risk factors and interventions for falls in order to prevent them from occurring in long-term care facilities. This study was grounded in the methodological approach of the Scottish Intercollegiate Guideline Network for establishing evidence-based guidelines: (1) establishment of the target population and scope of the guideline, (2) systematic literature review and critical analysis, (3) determination of the recommendation grade, (4) development of a draft nursing intervention guideline and algorithm, (5) expert evaluation of the draft nursing intervention guideline, and (6) confirmation of the final intervention guideline and completion of the algorithm. The resulting evidence-based fall prevention guideline consists of a three-step factor assessment and a three-step intervention approach. The resulting guideline was based on the literature and clinical experts. Further research is required to test the guideline's feasibility in across long term care facilities. This guideline can be used by nurses to screen patients who are at a high risk of falling to provide patient interventions to help prevent falls. Considering the high rate of falls at long-term care facilities and the absence of evidence-based guidelines to prevent them, additional studies on falls at long-term care facilities are necessary. Meanwhile, given prior research that indicates the importance of human resources in the application of such guidelines, continuous investigations are needed as to whether the research outcomes are actually conveyed to nurses. © 2014 International Council of Nurses.

Nootropic agents stimulate neurogenesis. Brain Cells, Inc.: WO2007104035.

Science.gov (United States)

Taupin, Philippe

2009-05-01

The application is in the field of adult neurogenesis, neural stem cells and cellular therapy. It aims to characterize the activity of nootropic agents on adult neurogenesis in vitro. Nootropic agents are substances improving cognitive and mental abilities. AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and nootropic agents were assessed for the potential to differentiate human neural progenitor and stem cells into neuronal cells in vitro. They were also tested for their behavioural activity on the novel object recognition task. AMPA, piracetam, FK-960 and SGS-111 induce and stimulate neuronal differentiation of human-derived neural progenitor and stem cells. SGS-111 increases the number of visits to the novel object. The neurogenic activity of piracetam and SGS-111 is mediated through AMPA receptor. The neurogenic activity of SGS-111 may contribute and play a role in its nootropic activity. These results suggest that nootropic agents may elicit some of their effects through their neurogenic activity. The application claims the use of nootropic agents for their neurogenic activity and for the treatment of neurological diseases, disorders and injuries, by stimulating or increasing the generation of neuronal cells in the adult brain.

Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine.

Science.gov (United States)

Sobanski, E; Leppämäki, S; Bushe, C; Berggren, L; Casillas, M; Deberdt, W

2015-11-01

Atomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns. From 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24 weeks; n=1443) and/or short-term (12 weeks; n=2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling. Based on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12 weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e.≥30% reduction in CAARS-Inv:SV total score, and CGI-S score≤3) were observed at 8 and 24 weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4. While many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24 weeks. Longer-term treatment may be associated with greater numbers of responders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

Science.gov (United States)

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

2011-01-01

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

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

Directory of Open Access Journals (Sweden)

Ine Rayen

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

Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

Directory of Open Access Journals (Sweden)

Irmgard eAmrein

2014-05-01

Full Text Available African mole-rats (family Bathyergidae are small to medium sized, long-lived and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of one year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin. Solitary Cape mole-rats (Georychus capensis, social highveld mole-rats (Cryptomys hottentotus pretoriae, and eusocial naked mole-rats (Heterocephalus glaber were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean

Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species.

Science.gov (United States)

Amrein, Irmgard; Becker, Anton S; Engler, Stefanie; Huang, Shih-Hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K

2014-01-01

African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents.

Regulation by commensal bacteria of neurogenesis in the subventricular zone of adult mouse brain.

Science.gov (United States)

Sawada, Naoki; Kotani, Takenori; Konno, Tasuku; Setiawan, Jajar; Nishigaito, Yuka; Saito, Yasuyuki; Murata, Yoji; Nibu, Ken-Ichi; Matozaki, Takashi

2018-04-15

In the mouse olfactory bulb (OB), interneurons such as granule cells and periglomerular cells are continuously replaced by adult-born neurons, which are generated in the subventricular zone (SVZ) of the brain. We have now investigated the role of commensal bacteria in regulation of such neuronal cell turnover in the adult mouse brain. Administration of mixture of antibiotics to specific pathogen-free (SPF) mice markedly attenuated the incorporation of bromodeoxyuridine (BrdU) into the SVZ cells. The treatment with antibiotics also reduced newly generated BrdU-positive neurons in the mouse OB. In addition, the incorporation of BrdU into the SVZ cells of germ-free (GF) mice was markedly reduced compared to that apparent for SPF mice. In contrast, the reduced incorporation of BrdU into the SVZ cells of GF mice was recovered by their co-housing with SPF mice, suggesting that commensal bacteria promote the incorporation of BrdU into the SVZ cells. Finally, we found that administration of ampicillin markedly attenuated the incorporation of BrdU into the SVZ cells of SPF mice. Our results thus suggest that ampicillin-sensitive commensal bacteria regulate the neurogenesis in the SVZ of adult mouse brain. Copyright © 2018 Elsevier Inc. All rights reserved.

Long-term maintenance of weight loss after lifestyle intervention in frail, obese older adults.

Science.gov (United States)

Waters, D L; Vawter, R; Qualls, C; Chode, S; Armamento-Villareal, R; Villareal, D T

2013-01-01

To determine if long-term weight loss with associated improvement in physical and metabolic health can be maintained after lifestyle intervention in frail, obese older adults. Thirty-month follow-up pilot study of a 1-year lifestyle intervention trial. Community. Sixteen frail, obese (body mass index=36±2 kg/m2) older (71±1 yr.) adults. Body weight and composition, physical function, markers of the metabolic syndrome, glucose and insulin response to an oral glucose tolerance test, bone mineral density (BMD), liver and renal function tests, and food diaries. At 30-month follow-up, weight (101.5±3.8 vs. 94.5±3.9 kg) and BMI (36.0 ±1.7 vs. 33.5±1.7 kg/m2) remained significantly below baseline (all plean mass (24.1±1.0 vs. 24.1±1.1kg, all p>0.05) occurred between 12 months (end of trial) and 30 months. Improvements in the physical performance test (PPT 27±0.7 vs. 30.2±0.6), insulin sensitivity (4.1±0.8 vs. 3.0±0.6), and insulin area under the curve (12484±2042 vs. 9270±1139 min.mg/dl) remained at 30 months compared to baseline (all pmaintenance of clinically important weight loss is possible in frail, obese older adults. Weight maintenance appears to be achieved through continued caloric restriction. Larger, long-term studies are needed to follow up on these findings and investigate mechanisms and behaviors underlying maintenance of weight loss and physical function.

Endogenous neurogenesis in the human brain following cerebral infarction.

Science.gov (United States)

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

2007-01-01

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

Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

Directory of Open Access Journals (Sweden)

Kathrin Hemmer

2014-09-01

Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

Parental divorce: long-term effects on mental health, family relations and adult sexual behavior.

Science.gov (United States)

Jónsson, F H; Njardvik, U; Olafsdóttir, G; Grétarsson, S J

2000-06-01

Specific long term effects of parental divorce were examined in a sample of 179 Icelanders, 20 to 30 years of age. The participants answered the Borromean Family Index, the Affect Balance Scale and a number of questions on sexual behavior and attitudes towards marriage and divorce. Results showed that compared to adults whose parents remained married, those of divorced parents reported more negative emotional experiences at the time of the study and had looser family ties. They also had greater number of short love affairs, had their first love affair at a younger age, had a greater number of sexual partners, and were younger at the time of their first sexual intercourse than adults whose parents remained married.

Long-term outcome of a cohort of adults with autism and intellectual disability: A pilot prospective study.

Science.gov (United States)

Fusar-Poli, Laura; Brondino, Natascia; Orsi, Paolo; Provenzani, Umberto; De Micheli, Andrea; Ucelli di Nemi, Stefania; Barale, Francesco; Politi, Pierluigi

2017-01-01

Autism spectrum disorders (ASD) are a long-life condition frequently associated with intellectual disability. To date, long-term outcome has been investigated mostly in ASD people with average or above-average intelligence and there is a paucity of data about autistic adults with comorbid intellectual disability. The aim of the present study is to assess long-term variations of adaptive abilities in a sample of autistic adults with intellectual disability and severe language impairment. 22 adults (17 males and 5 females) affected by autism and intellectual disability were recruited and evaluated after their admission in an Italian farm-community. Vineland Adaptive Behavior Scales (VABS) were used as outcome measure for adaptive abilities. After ten years the measurement was repeated in order to study the evolution of patients' skills along time. Additionally, sociodemographic variables, changes in medication and comorbidities were recorded. No statistically significant improvement neither deterioration was found according to VABS raw scores in the entire sample. On the contrary, a significant improvement was evident in standard scores for the Adaptive Behavior Composite Scale and for each domain. In general, our patients remained stable in adaptive abilities. However, our results are not generalisable to the entire autistic population, but only to inpatients with autism and comorbid intellectual disability. New measures should be developed in order to better assess changes in this particular population. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2018-01-01

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

High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention.

Science.gov (United States)

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

2017-08-01

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

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

International Nuclear Information System (INIS)

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

1991-01-01

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

Factors governing long-term adherence to a gluten-free diet in adult patients with coeliac disease.

Science.gov (United States)

Villafuerte-Galvez, J; Vanga, R R; Dennis, M; Hansen, J; Leffler, D A; Kelly, C P; Mukherjee, R

2015-09-01

A strict gluten-free diet is the cornerstone of treatment for coeliac disease. Studies of gluten-free diet adherence have rarely used validated instruments. There is a paucity of data on long-term adherence to the gluten-free diet in the adult population. To determine the long-term adherence to the gluten-free diet and potential associated factors in a large coeliac disease referral centre population. We performed a mailed survey of adults with clinically, serologically and histologically confirmed coeliac disease diagnosed ≥5 years prior to survey. The previously validated Celiac Disease Adherence Test was used to determine adherence. Demographic, socio-economic and potentially associated factors were analysed with adherence as the outcome. The response rate was 50.1% of 709 surveyed, the mean time on a gluten-free diet 9.9 ± 6.4 years. Adequate adherence (celiac disease adherence test score 75% of respondents. Perceived cost remains a barrier to adherence. Perceptions of effectiveness of gluten-free diet as well as its knowledge, are potential areas for intervention. © 2015 John Wiley & Sons Ltd.

The endogenous regenerative capacity of the damaged newborn brain: boosting neurogenesis with mesenchymal stem cell treatment

OpenAIRE

Donega, Vanessa; van Velthoven, Cindy TJ; Nijboer, Cora H; Kavelaars, Annemieke; Heijnen, Cobi J

2013-01-01

Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxia–ischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategie...

Hericium erinaceus Extract Reduces Anxiety and Depressive Behaviors by Promoting Hippocampal Neurogenesis in the Adult Mouse Brain.

Science.gov (United States)

Ryu, Sun; Kim, Hyoun Geun; Kim, Joo Youn; Kim, Seong Yun; Cho, Kyung-Ok

2018-02-01

Versatile biological activities of Hericium erinaceus (HE) have been reported in many brain diseases. However, roles of HE in major psychiatric disorders such as depression and anxiety remain to be investigated. Therefore, we evaluated whether HE could reduce anxiety and depressive behaviors in the adult mouse and its underlying mechanisms. Male C57BL/6 mice were administered HE (20 or 60 mg/kg, p.o.) or saline once a day for 4 weeks. Open field and tail suspension tests were performed 30 min after the last administration of HE, followed by forced swim test 2 days later. We found that chronic administration of HE showed anxiolytic and antidepressant-like effects. To elucidate possible mechanisms, proliferative activity of the hippocampal progenitor cells was assessed by immunohistochemistry of proliferating cell nuclear antigen (PCNA) and Ki67. Moreover, to evaluate neuronal survival in the dentate gyrus, 5-bromo-2'-deoxyuridine (BrdU) (120 mg/kg, i.p.) was given at the first day of HE administration, followed by isolation of the brains 4 weeks later. HE (60 mg/kg) increased the number of PCNA- and Ki67-positive cells in the subgranular zone of the hippocampus, indicating increased proliferation of hippocampal progenitors. In addition, BrdU- and BrdU/NeuN-positive cells in the dentate gyrus were significantly increased when treated with HE (60 mg/kg) compared with the saline-treated group, demonstrating enhanced neurogenesis by HE treatment. Taken together, the results indicate that chronic HE administration can exert anxiolytic and antidepressant-like effects, possibly by enhancing adult hippocampal neurogenesis.

Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation

Directory of Open Access Journals (Sweden)

Jessberger Sebastian

2006-11-01

Full Text Available Abstract Background In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle. Alternatively, the temporal course of morphological maturation might be subject to additional regulatory events. Results We found that (1 20% of the DCX population were precursor cells in cell cycle, whereas more than 70% were postmitotic, (2 the time span until newborn cells had reached the most mature stage associated with DCX expression varied between 3 days and several weeks, (3 positive or negative regulation of precursor cell proliferation did not alter the pattern and dynamics of dendrite development. Dendrite maturation was largely independent of close contacts to astrocytes. Conclusion These data imply that dendrite maturation of immature neurons is initiated at varying times after cell cycle exit, is variable in duration, and is controlled independently of the regulation of precursor cell proliferation. We conclude that in addition to the major regulatory events in cell proliferation and selective survival, additional micro-regulatory events influence the course of adult hippocampal neurogenesis.

A weak magnetic field inhibits hippocampal neurogenesis in SD rats

Science.gov (United States)

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

2017-12-01

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

Retrospective attention in short-term memory has a lasting effect on long-term memory across age.

Science.gov (United States)

Strunk, Jonathan; Morgan, Lauren; Reaves, Sarah; Verhaeghen, Paul; Duarte, Audrey

2018-04-13

Declines in both short- and long-term memory are typical of healthy aging. Recent findings suggest that retrodictive attentional cues ("retro-cues") that indicate the location of to-be-probed items in short-term memory (STM) have a lasting impact on long-term memory (LTM) performance in young adults. Whether older adults can also use retro-cues to facilitate both STM and LTM is unknown. Young and older adults performed a visual STM task in which spatially informative retro-cues or non-informative neutral-cues were presented during STM maintenance of real-world objects. We tested participants' memory at both STM and LTM delays for objects that were previously cued with retrodictive or neutral cues during STM order to measure the lasting impact of retrospective attention on LTM. Older adults showed reduced STM and LTM capacity compared to young adults. However, they showed similar magnitude retro-cue memory benefits as young adults at both STM and LTM delays. To the best of our knowledge, this is the first study to investigate whether retro-cues in STM facilitate the encoding of objects into LTM such that they are more likely to be subsequently retrieved by older adults. Our results support the idea that retrospective attention can be an effective means by which older adults can improve their short and long-term memory performance, even in the context of reduced memory capacity.

Long-term moderate alcohol consumption does not exacerbate age-related cognitive decline in healthy, community-dwelling older adults

Directory of Open Access Journals (Sweden)

Malaak Nasser Moussa

2015-01-01

Full Text Available Recent census data has found that roughly 40% of adults 65 years and older not only consume alcohol but also drink more of it than previous generations. Older drinkers are more vulnerable than younger counterparts to the psychoactive effects of alcohol due to natural biological changes that occur with aging. This study was specifically designed to measure the effect of long-term moderate alcohol consumption on cognitive health in older adult drinkers. An extensive battery of validated tests commonly used in aging and substance use literature was used to measure performance in specific cognitive domains, including working memory and attention. An age (young, old * alcohol consumption (light, moderate factorial study design was used to evaluate the main effects of age and alcohol consumption on cognitive performance. The focus of the study was then limited to light and moderate older drinkers, and whether or not long–term moderate alcohol consumption exacerbated age-related cognitive decline. No evidence was found to support the idea that long-term moderate alcohol consumption in older adults exacerbates age-related cognitive decline. Findings were specific to healthy community dwelling social drinkers in older age and they should not be generalized to individuals with other consumption patterns, like heavy drinkers, binge drinkers or ex-drinkers.

The effects of light therapy on depression and sleep disruption in older adults in a long-term care facility.

Science.gov (United States)

Wu, Mann-Chian; Sung, Huei-Chuan; Lee, Wen-Li; Smith, Graeme D

2015-10-01

This study aims to evaluate the effect of light therapy on depression and sleep disruption in older adults residing in a long-term care facility. Psychological morbidity is a problem commonly seen in older adults residing in long-term care facilities. Limited research has addressed the effect of light therapy on depression in this population. A quasi-experimental pretest and posttest design was used. Thirty-four participants in the experimental group received light therapy by sitting in front of a 10000-lux light box 30 min in the morning, three times a week for 4 weeks. Thirty-one participants in the control group received routine care without light therapy. Depression was measured by Geriatric Depression Scale-Short Form at baseline and week 4. After receiving 4 weeks of light therapy, the mean depression score in the experimental group decreased from 7.24 (SD3.42) at pretest to 5.91 (SD 3.40) at posttest, and had a significant reduction (t = 2.22, P = 0.03). However, there was no significant difference in depression score and sleep disruption between the experimental group and control group. Light therapy might have the potential to reduce depressive symptoms and sleep disruption and may be a viable intervention to improve mental health of older adults in the long-term care facilities. © 2014 Wiley Publishing Asia Pty Ltd.

Prevalence of Long-Term Opioid Use in Long-Stay Nursing Home Residents.

Science.gov (United States)

Hunnicutt, Jacob N; Chrysanthopoulou, Stavroula A; Ulbricht, Christine M; Hume, Anne L; Tjia, Jennifer; Lapane, Kate L

2018-01-01

Overall and long-term opioid use among older adults have increased since 1999. Less is known about opioid use in older adults in nursing homes (NHs). Cross-sectional. U.S. NHs (N = 13,522). Long-stay NH resident Medicare beneficiaries with a Minimum Data Set 3.0 (MDS) assessment between April 1, 2012, and June 30, 2012, and 120 days of follow-up (N = 315,949). We used Medicare Part D claims to measure length of opioid use in the 120 days from the index assessment (short-term: ≤30 days, medium-term: >30-89 days, long-term: ≥90 days), adjuvants (e.g., anticonvulsants), and other pain medications (e.g., corticosteroids). MDS assessments in the follow-up period were used to measure nonpharmacological pain management use. Modified Poisson models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for age, gender, race and ethnicity, cognitive and physical impairment, and long-term opioid use. Of all long-stay residents, 32.4% were prescribed any opioid, and 15.5% were prescribed opioids long-term. Opioid users (versus nonusers) were more commonly prescribed pain adjuvants (32.9% vs 14.9%), other pain medications (25.5% vs 11.0%), and nonpharmacological pain management (24.5% vs 9.3%). Long-term opioid use was higher in women (aPR = 1.21, 95% CI = 1.18-1.23) and lower in racial and ethnic minorities (non-Hispanic blacks vs whites: APR = 0.93, 95% CI = 0.90-0.94) and those with severe cognitive impairment (vs no or mild impairment, aPR = 0.82, 95% CI = 0.79-0.83). One in seven NH residents was prescribed opioids long-term. Recent guidelines on opioid prescribing for pain recommend reducing long-term opioid use, but this is challenging in NHs because residents may not benefit from nonpharmacological and nonopioid interventions. Studies to address concerns about opioid safety and effectiveness (e.g., on pain and functional status) in NHs are needed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics

ANOTHER "LETHAL TRIAD"-RISK FACTORS FOR VIOLENT INJURY AND LONG-TERM MORTALITY AMONG ADULT VICTIMS OF VIOLENT INJURY.

Science.gov (United States)

Laytin, Adam D; Shumway, Martha; Boccellari, Alicia; Juillard, Catherine J; Dicker, Rochelle A

2018-04-14

Mental illness, substance abuse, and poverty are risk factors for violent injury, and violent injury is a risk factor for early mortality that can be attenuated through hospital-based violence intervention programs. Most of these programs focus on victims under the age of 30 years. Little is known about risk factors or long-term mortality among older victims of violent injury. To explore the prevalence of risk factors for violent injury among younger (age < 30 years) and older (age 30 ≥ years) victims of violent injury, to determine the long-term mortality rates in these age groups, and to explore the association between risk factors for violent injury and long-term mortality. Adults with violent injuries were enrolled between 2001 and 2004. Demographic and injury data were recorded on enrollment. Ten-year mortality rates were measured. Descriptive analysis and logistic regression were used to compare older and younger subjects. Among 541 subjects, 70% were over age 30. The overall 10-year mortality rate was 15%, and was much higher than in the age-matched general population in both age groups. Risk factors for violent injury including mental illness, substance abuse, and poverty were prevalent, especially among older subjects, and were each independently associated with increased risk of long-term mortality. Mental illness, substance abuse, and poverty constitute a "lethal triad" that is associated with an increased risk of long-term mortality among victims of violent injury, including both younger adults and those over age 30 years. Both groups may benefit from targeted risk-reduction efforts. Emergency department visits offer an invaluable opportunity to engage these vulnerable patients. Copyright © 2018 Elsevier Inc. All rights reserved.

P2X7 receptor inhibition increases CNTF in the subventricular zone, but not neurogenesis or neuroprotection after stroke in adult mice.

Science.gov (United States)

Kang, Seong Su; Keasey, Matthew Phillip; Hagg, Theo

2013-10-01

Increasing endogenous ciliary neurotrophic factor (CNTF) expression with a pharmacological agent might be beneficial after stroke as CNTF both promotes neurogenesis and, separately, is neuroprotective. P2X7 purinergic receptor inhibition is neuroprotective in rats and increases CNTF release in rat CMT1A Schwann cells. We, first, investigated the role of P2X7 in regulating CNTF and neurogenesis in adult mouse subventricular zone (SVZ). CNTF expression was increased by daily intravenous injections of the P2X7 antagonist Brilliant Blue G (BBG) in naïve C57BL/6 or Balb/c mice over 3 days. Despite the ∼40-60 % increase or decrease in CNTF with BBG or the agonist BzATP, respectively, the number of proliferated BrdU+SVZ nuclei did not change. BBG failed to increase FGF2, which is involved in CNTF-regulated neurogenesis, but induced IL-6, LIF, and EGF, which are known to reduce SVZ proliferation. Injections of IL-6 next to the SVZ induced CNTF and FGF2, but not proliferation, suggesting that IL-6 counteracts their neurogenesis-inducing effects. Following ischemic injury of the striatum by middle cerebral artery occlusion (MCAO), a 3-day BBG treatment increased CNTF in the medial penumbra containing the SVZ. BBG also induced CNTF and LIF, which are known to be protective following stroke, in the whole striatum after MCAO, but not GDNF or BDNF. However, BBG treatment did not reduce the lesion area or apoptosis in the penumbra. Even so, this study shows that P2X7 can be targeted with systemic drug treatments to differentially regulate neurotrophic factors in the brain following stroke.

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

Science.gov (United States)

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

2012-03-02

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

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

Science.gov (United States)

Sobhan, Praveen K; Funa, Keiko

2017-01-01

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

Cystic fibrosis in adults. Short-term and long-term reproducibility of the Brody score for lung morphology in low-dose MDCT scans

Energy Technology Data Exchange (ETDEWEB)

Weber, K.; Paolini, M.; Schmitz, M.; Coppenrath, E.; Reiser, M.; Mueller-Lisse, U.G. [Ludwig-Maximilians-Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie; Fischer, R.; Huber, R. [Ludwig-Maximilians-Univ. Muenchen (Germany). Medical Hospital V

2014-01-15

Purpose: The semi-quantitative Brody score measures the severity of cystic fibrosis (CF)-related lung disease. We investigated the short-term (28 - 60 days) and long-term (2 - 7 years) intra- and inter-observer reproducibility of the Brody score in low-dose multidetector row computed tomography examinations performed in inspiration (LDCTs) of adult CF patients. Materials and Methods: Composite Brody scores and respective underlying bronchiectasis, mucus plugging, peribronchial thickening, parenchymal opacity, and hyperinflation subscores were evaluated twice (time interval, 1 - 84 months) by each of 3 independent radiologists (1 - 20 years of professional diagnostic radiology experience) in LDCTs (4 - 64 rows, 120 KVp, 10 - 15 mAs/slice, CTDIw approx. 1.0 mGy, effective dose approx. 0.5 mSv) of 15 adult patients with CF-related lung disease (8 female, 7 male, age, 18 - 50 years, mean, 33 years). Results: The average reproducibility of the Brody score was within +/-7 % (range, 2 - 30 %) between radiologists, and +/-6 % (3 - 12 %) within radiologists (short-term, 28 - 60 days, 4 %, 0 - 12 %, long-term, 2 - 7 years, 12 %, 1 - 36 %). For the different subscores, the reproducibility was within +/-25 % (15 - 41 %) between radiologists and +/-23 % (12 - 46 %) within radiologists. Conclusion: The Brody score shows high average inter-observer reproducibility in LDCTs of adult CF patients. The Brody score also demonstrates high average intra-observer reproducibility if subsequent assessments are made within 28 - 61 days. With time intervals of 2 - 7 years between subsequent evaluations, however, intra-observer reproducibility decreases. Respective subscores each demonstrate lower intra- and inter-observer reproducibility than does the composite Brody score. (orig.)

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

Directory of Open Access Journals (Sweden)

Laura B. Ngwenya

2018-01-01

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

Mitochondrial dynamics in the regulation of neurogenesis: From development to the adult brain.

Science.gov (United States)

Khacho, Mireille; Slack, Ruth S

2018-01-01

Mitochondria are classically known to be the cellular energy producers, but a renewed appreciation for these organelles has developed with the accumulating discoveries of additional functions. The importance of mitochondria within the brain has been long known, particularly given the high-energy demanding nature of neurons. The energy demands imposed by neurons require the well-orchestrated morphological adaptation and distribution of mitochondria. Recent studies now reveal the importance of mitochondrial dynamics not only in mature neurons but also during neural development, particularly during the process of neurogenesis and neural stem cell fate decisions. In this review, we will highlight the recent findings that illustrate the importance of mitochondrial dynamics in neurodevelopment and neural stem cell function. Developmental Dynamics 247:47-53, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

Science.gov (United States)

Fidaleo, Marco; Cavallucci, Virve; Pani, Giovambattista

2017-10-01

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

Impact of Short- and Long-term Tai Chi Mind-Body Exercise Training on Cognitive Function in Healthy Adults: Results From a Hybrid Observational Study and Randomized Trial.

Science.gov (United States)

Walsh, Jacquelyn N; Manor, Brad; Hausdorff, Jeffrey; Novak, Vera; Lipsitz, Lewis; Gow, Brian; Macklin, Eric A; Peng, Chung-Kang; Wayne, Peter M

2015-07-01

Cognitive decline amongst older adults is a significant public health concern. There is growing interest in behavioral interventions, including exercise, for improving cognition. Studies to date suggest tai chi (TC) may be a safe and potentially effective exercise for preserving cognitive function with aging; however, its short-term and potential long-term impact on physically active, healthy adults is unclear. To compare differences in cognitive function among long-term TC expert practitioners and age-matched and gender-matched TC-naïve adults and to determine the effects of short-term TC training on measures of cognitive function in healthy, nonsedentary adults. A hybrid design including an observational comparison and a 2-arm randomized clinical trial (RCT). Healthy, nonsedentary, TC-naive adults (50 y-79 y) and age-matched and gender-matched long-term TC experts. A cross-sectional comparison of cognitive function in healthy TC-naïve (n=60) and TC expert (24.5 y ÷ 12 y experience; n=27) adults: TC-naïve adults then completed a 6-month, 2-arm, wait-list randomized clinical trial of TC training. Six measures of cognitive function were assessed for both cross-sectional and longitudinal comparisons. TC experts exhibited trends towards better scores on all cognitive measures, significantly so for category fluency (P=.01), as well as a composite z score summarizing all 6 cognitive assessments (P=.03). In contrast, random assignment to 6 months of TC training in TC-naïve adults did not significantly improve any measures of cognitive function. In healthy nonsedentary adults, long-term TC training may help preserve cognitive function; however, the effect of short-term TC training in healthy adults remains unclear. ClinicalTrials.gov NCT01340365.

Long-term mental wellbeing of adolescents and young adults diagnosed with venous thromboembolism: results from a multistage mixed methods study.

Science.gov (United States)

Højen, A A; Sørensen, E E; Dreyer, P S; Søgaard, M; Larsen, T B

2017-12-01

Essentials Long-term mental wellbeing of adolescents and young adults with venous thromboembolism is unclear. This multistage mixed methods study was based on Danish nationwide registry data and interviews. Mental wellbeing is negatively impacted in the long-term and uncertainty of recurrence is pivotal. The perceived health threat is more important than disease severity for long-term mental wellbeing. Background Critical and chronic illness in youth can lead to impaired mental wellbeing. Venous thromboembolism (VTE) is a potentially traumatic and life-threatening condition. Nonetheless, the long-term mental wellbeing of adolescents and young adults (AYAS) with VTE is unclear. Objectives To investigate the long-term mental wellbeing of AYAS (aged 13-33 years) diagnosed with VTE. Methods We performed a multistage mixed method study based on data from the Danish nationwide health registries, and semistructured interviews with 12 AYAS diagnosed with VTE. An integrated mixed methods interpretation of the findings was conducted through narrative weaving and joint displays. Results The integrated mixed methods interpretation showed that the mental wellbeing of AYAS with VTE had a chronic perspective, with a persistently higher risk of psychotropic drug purchase among AYAS with a first-time diagnosis of VTE than among sex-matched and age-matched population controls and AYAS with a first-time diagnosis of insulin-dependent diabetes mellitus. Impaired mental wellbeing was largely connected to a fear of recurrence and concomitant uncertainty. Therefore, it was important for the long-term mental wellbeing to navigate uncertainty. The perceived health threat played a more profound role in long-term mental wellbeing than disease severity, as the potential life threat was the pivot which pointed back to the initial VTE and forward to the perception of future health threat and the potential risk of dying of a recurrent event. Conclusion Our findings show that the long-term

Long-Term Alterations in Neural and Endocrine Processes Induced by Motherhood

Science.gov (United States)

Bridges, Robert S.

2015-01-01

The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female’s biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. PMID:26388065

Impact of trichostatin A and sodium valproate treatment on post-stroke neurogenesis and behavioral outcomes in immature mice

Directory of Open Access Journals (Sweden)

Shanu eGeorge

2013-08-01

Full Text Available Stroke in the neonatal brain frequently results in neurologic impairments including cognitive disability. We investigated the effect of long-term sodium valproate (valproate and Trichostatin A (TSA treatment upon post-stroke neurogenesis in the dentate gyrus (DG of stroke-injured immature mice. Decreased or abnormal integration of newborn DG neurons into hippocampal circuits can result in impaired visual-spatial function, abnormal modulation of mood-related behaviors, and the development of post-stroke epilepsy. Unilateral carotid ligation of P12 CD1 mice was followed by treatment with valproate, TSA, or vehicle for 2 weeks, BrdU administration for measurement of neurogenesis, and perfusion at P42 or P60. Behavior testing was conducted from P38-42. No detrimental effects on behavior testing were noted with TSA treatment, but mildly impaired cognitive function was noted with valproate-treated injured animals compared to normal animals. Significant increases in DG neurogenesis with both TSA and valproate treatment were noted with later administration of BrdU. Increased mortality and impaired weight gain was noted in the valproate-treated ligated animals, but not in the TSA-treated animals. In summary, the impact of HDAC inhibition upon post-stroke SGZ neurogenesis is likely to depend on the age of the animal at the time point when neurogenesis is assessed, duration of HDAC inhibition before BrdU labeling, and/or the stage in the evolution of the injury.

Cardiovascular disease is the main cause of long-term excess mortality after ischemic stroke in young adults

NARCIS (Netherlands)

Rutten-Jacobs, L.C.A.; Arntz, R.M.; Maaijwee, N.A.M.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.; Dijk, E.J. van; Leeuw, F.E. de

2015-01-01

Adults with stroke at a young age (18-50 years) remain at an increased risk of death for decades. It is unclear what cause underlies this long-term excess mortality and whether this is sex and time specific. Therefore, we investigated sex-specific temporal changes in cause of death after transient

Comparison of major depressive disorder and subthreshold depression among older adults in community long-term care.

Science.gov (United States)

Lee, Mi Jin; Hasche, Leslie K; Choi, Sunha; Proctor, Enola K; Morrow-Howell, Nancy

2013-01-01

This study extends existing knowledge regarding the continuum between major depression (MD) and subthreshold depression (SD) by examining differences in symptomology and associative factors for a subpopulation of older adults with functional disability. Our sample consisted of clients age 60 and above entering public community long term care derived from the baseline survey of a longitudinal study (315 non-depressed, 74 MD, and 221 SD). We used the Diagnostic Interview Schedule to establish diagnoses of MD, the Center for Epidemiological Studies Depression Scale (CES-D) to assess SD, and other self-report measures to explore potential associative factors of demographics, comorbidity, social support, and stressors. No differences in CES-D identified symptoms occurred between the two groups. MD and SD were both associated with lower education, poorer social support, more severe medical conditions, and higher stress when compared to non-depressed older adults. Younger age and being female were associated solely with MD; whereas, worse perceived health and more trouble affording food were associated solely with SD. The only associative factor significantly different between MD and SD was age. Those with MD were more likely to be younger than those with SD. Our findings of symptom profiles and associative factors lend support to the continuum notion of depression. Identification of only older adults within the community long-term care service system who meet criteria for MD would leave many older adults, who also face multiple comorbidities, high levels of stress and social isolation, and substantial depressive symptoms undiagnosed and untreated.

Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

Science.gov (United States)

Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

2014-09-09

Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Food restriction reduces neurogenesis in the avian hippocampal formation.

Directory of Open Access Journals (Sweden)

Barbara-Anne Robertson

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

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

Science.gov (United States)

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

2018-03-01

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

Regulation of hippocampal neurogenesis by systemic factors including stress, glucocorticoids, sleep, and inflammation

NARCIS (Netherlands)

Lucassen, P.J.; Oomen, C.; van Dam, A.-M.; Czéh, B.; Gage, F.H.; Kempermann, G.; Song, H.

2008-01-01

This review summarizes and discusses the regulation of adult neurogenesis and hippocampal cellular plasticity by systemic factors. We focus on the role of stress, glucocorticoids, and related factors such as sleep deprivation and inflammation.

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

Science.gov (United States)

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

2016-02-17

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

CENTRAL DIABETES INSIPIDUS: CLINICAL CHARACTERISTICS AND LONG-TERM COURSE IN A LARGE COHORT OF ADULTS.

Science.gov (United States)

Masri-Iraqi, Hiba; Hirsch, Dania; Herzberg, Dana; Lifshitz, Avner; Tsvetov, Gloria; Benbassat, Carlos; Shimon, Ilan

2017-05-01

Central diabetes insipidus (CDI) is a rare heterogeneous condition with various underlying causes. This study sought to increase the still-limited data on the clinical characteristics and long-term course in adults diagnosed with CDI. Data on demographics, presentation, imaging findings, affected pituitary axes, treatment, and complications were collected retrospectively from the files of 70 adult patients with CDI followed at a referral endocrine clinic. Forty women and 30 men were included. Mean age was 46.8 ± 15 years at the time of this study and 29.3 ± 20 years at CDI diagnosis. Twenty-eight patients were diagnosed in childhood. Forty patients (57%) acquired CDI following surgery. Main sellar pathologies were: craniopharyngioma, 17 patients (11 diagnosed in childhood); Langerhans histiocytosis, 10 patients (5 diagnosed in childhood); 7 patients (all diagnosed as adults) had a growth hormone-secreting adenoma; 12 patients (17%; 6 diagnosed in childhood) had idiopathic CDI. At least one anterior pituitary axis was affected in 73% of the cohort: 59% had growth hormone deficiency, 56% hypogonadism, 55% central hypothyroidism, 44% adrenocorticotropic hormone-cortisol deficiency. Patients with postoperative/trauma CDI (n = 44) tended to have multiple anterior pituitary axes deficits compared to the nonsurgical group of patients. All patients were treated with vasopressin preparations, mostly nasal spray. Hyponatremia developed in 32 patients, more in women, and was severe (150 mEq/L) was noticed in 5 patients. Overall, the calculated complication rate was 22 in 1,250 treatment-years. Most adult patients with CDI have anterior pituitary dysfunction. Stability is usually achieved with long-term treatment. Women were more susceptible to desmopressin complications, albeit with an overall relatively low complication rate. ACTH = adrenocorticotropic hormone CDI = central diabetes insipidus GH = growth hormone MRI = magnetic resonance imaging.

Long-term care services and support systems for older adults: The role of technology.

Science.gov (United States)

Czaja, Sara J

2016-01-01

The aging of the population, especially the increase in the "oldest old," is a remarkable achievement that presents both opportunities and challenges for policymakers, researchers, and society. Although many older adults enjoy relatively good health into their later years, many have one or more chronic conditions or diseases and need help with disease management activities or activities important to independent living. Technology is playing an increasingly important role in the health care arena and is becoming ubiquitous in health management activities. There are a variety of technology applications that can be used to enhance the mobility and quality of life of people who have limitations and help to foster the ability of those with chronic conditions to remain at home. Technology applications can also provide a central role in providing support to family caregivers in terms of enhancing access to information and community resources and connections to formal and informal support services. Monitoring technologies may also allow caregivers to check on the status or activities of their loved one while they are at work or at a distant location. Furthermore, telemedicine applications can aid the ability of care providers to monitor patients and deliver health services. The objective of this article is to highlight the potential role that technology can play in the provision of long-term support for older adults and their families. Challenges and barriers that currently limit the full potential of technology to be realized for these populations will also be discussed. Finally the role of psychological science toward maximizing the potential of technology applications in enhancing long term care and support services will be highlighted. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Caffeine alters proliferation of neuronal precursors in the adult hippocampus

OpenAIRE

Wentz, Christian T.; Magavi, Sanjay S.P.

2009-01-01

Neurogenesis continues through adulthood in the hippocampus and olfactory bulb of mammals. Adult neurogenesis has been implicated in learning and memory, and linked with depression. Hippocampal neurogenesis is increased in response to a number of stimuli, including exposure to an enriched environment, increased locomotor activity, and administration of antidepressants. Adult neurogenesis is depressed in response to aging, stress and sleep deprivation. Intriguingly, caffeine modulates a number...

Musical and Verbal Memory in Alzheimer's Disease: A Study of Long-Term and Short-Term Memory

Science.gov (United States)

Menard, Marie-Claude; Belleville, Sylvie

2009-01-01

Musical memory was tested in Alzheimer patients and in healthy older adults using long-term and short-term memory tasks. Long-term memory (LTM) was tested with a recognition procedure using unfamiliar melodies. Short-term memory (STM) was evaluated with same/different judgment tasks on short series of notes. Musical memory was compared to verbal…

Experiences with late effects-related care and preferences for long-term follow-up care among adult survivors of childhood lymphoma.

Science.gov (United States)

Lie, Hanne C; Mellblom, Anneli V; Brekke, Mette; Finset, Arnstein; Fosså, Sophie D; Kiserud, Cecilie E; Ruud, Ellen; Loge, Jon H

2017-08-01

Given childhood cancer survivors' risk of treatment-induced late effects, long-term follow-up care is recommended. We explored experiences with late effects-related care and preferences for long-term follow-up care among adult survivors of childhood malignant lymphoma in Norway. We conducted five focus group interviews with 34 survivors (19 females; 21 Hodgkin/13 non-Hodgkin lymphoma survivors; mean age 39 years; mean time from diagnosis 26 years). Data was analyzed using principles of thematic analysis. Two main themes were identified: (1) the survivors' experiences with late effects-related care and (2) their preferences for long-term follow-up care. Most of the survivors were dissatisfied with their late effects-related care due to perceptions of poor coordination of healthcare needs in a fragmented system, combined with a perceived lack of knowledge of late effects among themselves and general practitioners (GPs). All survivors valued long-term follow-up care. Oncologists were the preferred care providers, but GPs were considered acceptable providers if they had sufficient knowledge of late effects and routine examinations, short waiting times, and improved GP-oncologist collaboration. Our results suggest that a shared care model of long-term follow-up care involving specialists, GPs, and the survivors themselves is likely to fulfill several of the currently unmet needs among adult survivors of childhood cancers. Improved patient education about late effects and follow-up care would aid self-management. The survivors' concerns regarding lack of sufficient knowledge of late effects among GPs suggest a need for improving access to, and dissemination of, information of late effects.

Long-term moderate alcohol consumption does not exacerbate age-related cognitive decline in healthy, community-dwelling older adults

OpenAIRE

Moussa, Malaak N.; Simpson, Sean L.; Mayhugh, Rhiannon E.; Grata, Michelle E.; Burdette, Jonathan H.; Porrino, Linda J.; Laurienti, Paul J.

2015-01-01

Recent census data has found that roughly 40% of adults 65 years and older not only consume alcohol but also drink more of it than previous generations. Older drinkers are more vulnerable than younger counterparts to the psychoactive effects of alcohol due to natural biological changes that occur with aging. This study was specifically designed to measure the effect of long-term moderate alcohol consumption on cognitive health in older adult drinkers. An extensive battery of validated tests c...

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

Directory of Open Access Journals (Sweden)

Daniel M Iascone

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

The reduction of adult neurogenesis in depression impairs the retrieval of new as well as remote episodic memory.

Science.gov (United States)

Fang, Jing; Demic, Selver; Cheng, Sen

2018-01-01

Major depressive disorder (MDD) is associated with an impairment of episodic memory, but the mechanisms underlying this deficit remain unclear. Animal models of MDD find impaired adult neurogenesis (AN) in the dentate gyrus (DG), and AN in DG has been suggested to play a critical role in reducing the interference between overlapping memories through pattern separation. Here, we study the effect of reduced AN in MDD on the accuracy of episodic memory using computational modeling. We focus on how memory is affected when periods with a normal rate of AN (asymptomatic states) alternate with periods with a low rate (depressive episodes), which has never been studied before. Also, unlike previous models of adult neurogenesis, which consider memories as static patterns, we model episodic memory as sequences of neural activity patterns. In our model, AN adds additional random components to the memory patterns, which results in the decorrelation of similar patterns. Consistent with previous studies, higher rates of AN lead to higher memory accuracy in our model, which implies that memories stored in the depressive state are impaired. Intriguingly, our model makes the novel prediction that memories stored in an earlier asymptomatic state are also impaired by a later depressive episode. This retrograde effect exacerbates with increased duration of the depressive episode. Finally, pattern separation at the sensory processing stage does not improve, but rather worsens, the accuracy of episodic memory retrieval, suggesting an explanation for why AN is found in brain areas serving memory rather than sensory function. In conclusion, while cognitive retrieval biases might contribute to episodic memory deficits in MDD, our model suggests a mechanistic explanation that affects all episodic memories, regardless of emotional relevance.

The reduction of adult neurogenesis in depression impairs the retrieval of new as well as remote episodic memory

Science.gov (United States)

Fang, Jing; Demic, Selver; Cheng, Sen

2018-01-01

Major depressive disorder (MDD) is associated with an impairment of episodic memory, but the mechanisms underlying this deficit remain unclear. Animal models of MDD find impaired adult neurogenesis (AN) in the dentate gyrus (DG), and AN in DG has been suggested to play a critical role in reducing the interference between overlapping memories through pattern separation. Here, we study the effect of reduced AN in MDD on the accuracy of episodic memory using computational modeling. We focus on how memory is affected when periods with a normal rate of AN (asymptomatic states) alternate with periods with a low rate (depressive episodes), which has never been studied before. Also, unlike previous models of adult neurogenesis, which consider memories as static patterns, we model episodic memory as sequences of neural activity patterns. In our model, AN adds additional random components to the memory patterns, which results in the decorrelation of similar patterns. Consistent with previous studies, higher rates of AN lead to higher memory accuracy in our model, which implies that memories stored in the depressive state are impaired. Intriguingly, our model makes the novel prediction that memories stored in an earlier asymptomatic state are also impaired by a later depressive episode. This retrograde effect exacerbates with increased duration of the depressive episode. Finally, pattern separation at the sensory processing stage does not improve, but rather worsens, the accuracy of episodic memory retrieval, suggesting an explanation for why AN is found in brain areas serving memory rather than sensory function. In conclusion, while cognitive retrieval biases might contribute to episodic memory deficits in MDD, our model suggests a mechanistic explanation that affects all episodic memories, regardless of emotional relevance. PMID:29879169

Long-Term Effect of Maxillary Distraction Osteogenesis (DO) on Nasal Index in Adult Patients with Cleft Lip and Palate Deformities.

Science.gov (United States)

Jena, Ashok Kumar; Rattan, Vidya; Singh, Satinder Pal; Utreja, Ashok Kumar; Sombir, Singh

2016-03-01

To test the hypothesis that there is no immediate and long-term effects of maxillary distraction osteogenesis (DO) on nasal index among adult subjects with cleft lip and palate deformities. Twelve adult subjects in the age range of 17-20 years with complete unilateral cleft lip and palate underwent advancement of maxilla by DO. The immediate and long-term effects of maxillary DO on nasal index were evaluated from extra-oral full face frontal photographs recorded prior to DO (T0), at the end of active DO (T1) and at least 2-years after the DO (T2). The ANOVA, Post Hoc test (Bonferroni) and Pearson correlation coefficients were used. The probability value (P value) 0.05 was considered as statistically significant. SNM angle and Ptm-M distance increased significantly by DO (P distraction (T1) and by 12.69 to 97.84 ± 9.14 % at the end of long-term follow-up (T2). The correlation between sagittal maxillary advancement and nasal index was statistically significant (P maxillary advancement, the nasal index increased by 1.38 % and 1.8 % at the end of active distraction and long-term follow-up respectively. The advancement of maxilla by distraction osteogenesis among subjects with cleft lip and palate deformities increased nasal index significantly.

Leisure time physical activity among older adults with long-term spinal cord injury.

Science.gov (United States)

Jörgensen, S; Martin Ginis, K A; Lexell, J

2017-09-01

Cross-sectional. To describe participation in leisure time physical activity (LTPA) (amount, intensity and type) among older adults with long-term spinal cord injury (SCI), and to investigate the associations with sociodemographics, injury characteristics and secondary health conditions (SHCs). Home settings in southern Sweden. Data from the Swedish Aging with Spinal Cord Injury Study (SASCIS). The physical activity recall assessment for people with SCI was used to assess LTPA among 84 men and 35 women (mean age 63.5 years, mean time since injury 24 years, injury levels C1-L5, American Spinal Injury Association Impairment Scale A-D). Associations were analyzed statistically using hierarchical multivariable regression. Twenty-nine percent reported no LTPA, whereas 53% performed moderate-to-heavy intensity LTPA. The mean minutes per day of total LTPA was 34.7 (±41.5, median 15, range 0-171.7) and of moderate-to-heavy LTPA 22.5 (±35.1, median 5.0, range 0-140.0). The most frequently performed activities were walking and wheeling. Sociodemographics, injury characteristics and SHCs (bowel-related and bladder-related problems, spasticity and pain) explained 10.6% and 13.4%, respectively, of the variance in total and moderate-to-heavy LTPA. Age and wheelchair use were significantly, negatively associated with total LTPA. Women, wheelchair users and employed participants performed significantly less moderate-to-heavy LTPA than men, those using walking devices/no mobility device and unemployed participants. Many older adults with long-term SCI do not reach the amount or intensity of LTPA needed to achieve fitness benefits. Research is needed on how to increase LTPA and to identify modifiable factors that could enhance their participation.

Effect of long-term outdoor air pollution and noise on cognitive and psychological functions in adults.

Science.gov (United States)

Tzivian, Lilian; Winkler, Angela; Dlugaj, Martha; Schikowski, Tamara; Vossoughi, Mohammad; Fuks, Kateryna; Weinmayr, Gudrun; Hoffmann, Barbara

2015-01-01

It has been hypothesized that air pollution and ambient noise might impact neurocognitive function. Early studies mostly investigated the associations of air pollution and ambient noise exposure with cognitive development in children. More recently, several studies investigating associations with neurocognitive function, mood disorders, and neurodegenerative disease in adult populations were published, yielding inconsistent results. The purpose of this review is to summarize the current evidence on air pollution and noise effects on mental health in adults. We included studies in adult populations (≥18 years old) published in English language in peer-reviewed journals. Fifteen articles related to long-term effects of air pollution and eight articles on long-term effects of ambient noise were extracted. Both exposures were separately shown to be associated with one or several measures of global cognitive function, verbal and nonverbal learning and memory, activities of daily living, depressive symptoms, elevated anxiety, and nuisance. No study considered both exposures simultaneously and few studies investigated progression of neurocognitive decline or psychological factors. The existing evidence generally supports associations of environmental factors with mental health, but does not suffice for an overall conclusion about the independent effect of air pollution and noise. There is a need for studies investigating simultaneously air pollution and noise exposures in association mental health, for longitudinal studies to corroborate findings from cross-sectional analyses, and for parallel toxicological and epidemiological studies to elucidate mechanisms and pathways of action. Copyright © 2014 Elsevier GmbH. All rights reserved.

Prolonged Running, not Fluoxetine Treatment, Increases Neurogenesis, but does not Alter Neuropathology, in the 3xTg Mouse Model of Alzheimer's Disease.

NARCIS (Netherlands)

Marlatt, M.W.; Potter, M.C.; Bayer, T.A.; van Praag, H.; Lucassen, P.J.

2013-01-01

Reductions in adult neurogenesis have been documented in the original 3xTg mouse model of Alzheimer's disease (AD), notably occurring at the same age when spatial memory deficits and amyloid plaque pathology appeared. As this suggested reduced neurogenesis was associated with behavioral deficits, we

The hippocampus of the eastern rock sengi: cytoarchitecture, markers of neuronal function, principal cell numbers and adult neurogenesis

Directory of Open Access Journals (Sweden)

Lutz eSlomianka

2013-10-01

Full Text Available The brains of sengis (elephant shrews, order Macroscelidae have long been known to contain a hippocampus that in terms of allometric progression indices is larger than that of most primates and equal in size to that of humans. In this report, we provide descriptions of hippocampal cytoarchitecture in the eastern rock sengi (Elephantulus myurus, of the distributions of hippocampal calretinin, calbindin, parvalbumin and somatostatin, of principal neuron numbers and of cell numbers related to proliferation and neuronal differentiation in adult hippocampal neurogenesis. Sengi hippocampal cytoarchitecture is an amalgamation of characters that are found in CA1 of, e.g., guinea pig and rabbits and in CA3 and dentate gyrus of primates. Correspondence analysis of total cell numbers and quantitative relations between principal cell populations relate this sengi to macaque monkeys and domestic pigs, and distinguish the sengi from distinct patterns of relations found in humans, dogs and murine rodents. Calretinin and calbindin are present in some cell populations that also express these proteins in other species, e.g., interneurons at the stratum oriens/alveus border or temporal hilar mossy cells, but neurons expressing these markers are often scarce or absent in other layers. The distributions of parvalbumin and somatostatin resemble those in other species. Normalized numbers of PCNA+ proliferating cells and doublecortin+ differentiating cells of neuronal lineage fall within the overall ranges of murid rodents, but differed from three murid species captured in the same habitat in that fewer doublecortin+ cells relative to PCNA+ were observed . The large and well-differentiated sengi hippocampus is not accompanied by correspondingly sized cortical and subcortical limbic areas that are the main hippocampal sources of afferents and targets of efferents. This points to intrinsic hippocampal information processing as the selective advantage of the large sengi

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

Science.gov (United States)

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

2014-06-24

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

Long-term prognosis of transient lone bilateral blindness in adolescents and young adults.

Science.gov (United States)

Bower, S; Dennis, M; Warlow, C; Jordan, N; Sagar, H

1994-01-01

We describe a group of 14 patients aged 8-38 years at presentation who had one or more sudden transient attacks of bilateral blindness. Eight patients described bilateral blindness as their only symptom whereas six others experienced some mild associated symptoms. Visual loss always developed within seconds and attacks were often precipitated by exercise, stress, or postural change. Of 13 patients available for review, none suffered a major vascular event during a mean follow up of 10 years. When adolescents and young adults present with transient bilateral blindness, investigations are unlikely to reveal a cause and the long-term prognosis appears benign. PMID:8006656

Effects of exercise on neurogenesis in the dentate gyrus and ability of learning and memory after hippocampus lesion in adult rats

Institute of Scientific and Technical Information of China (English)

Lin CHEN; Shan GONG; Li-Dong SHAN; Wei-Ping XU; Yue-Jin ZHANG; Shi-Yu GUO; Tadashi Hisamitsu; Qi-Zhang YIN; Xing-Hong JIANG

2006-01-01

Objective To explore the effects of exercise on dentate gyrus (DG) neurogenesis and the ability of learning and memory in hippocampus-lesioned adult rats. Methods Hippocampus lesion was produced by intrahippocampal microinjection of kainic acid (KA). Bromodeoxyuridine (BrdU) was used to label dividing cells. Y maze test was used to evaluate the ability of learning and memory. Exercise was conducted in the form of forced running in a motor-driven running wheel. The speed of wheel revolution was regulated at 3 kinds of intensity: lightly running, moderately running, or heavily running. Results Hippocampus lesion could increase the number of BrdU-labeled DG cells, moderately running after lesion could further enhance the number of BrdU-labeled cells and decrease the error number (EN) in Y maze test,while neither lightly running, nor heavily running had such effects. There was a negative correlation between the number of DG BrdU-labeled cells and the EN in the Y maze test after running. Conclusion Moderate exercise could enhance the DG neurogenesis and ameliorate the ability of learning and memory in hippocampus-lesioned rats.

Long-Term Natural History of Adult Wolff-Parkinson-White Syndrome Patients Treated With and Without Catheter Ablation.

Science.gov (United States)

Bunch, T Jared; May, Heidi T; Bair, Tami L; Anderson, Jeffrey L; Crandall, Brian G; Cutler, Michael J; Jacobs, Victoria; Mallender, Charles; Muhlestein, Joseph B; Osborn, Jeffrey S; Weiss, J Peter; Day, John D

2015-12-01

There are a paucity of data about the long-term natural history of adult Wolff-Parkinson-White syndrome (WPW) patients in regard to risk of mortality and atrial fibrillation. We sought to describe the long-term outcomes of WPW patients and ascertain the impact of ablation on the natural history. Three groups of patients were studied: 2 WPW populations (ablation: 872, no ablation: 1461) and a 1:5 control population (n=11 175). Long-term mortality and atrial fibrillation rates were determined. The average follow-up for the WPW group was 7.9±5.9 (median: 6.9) years and was similar between the ablation and nonablation groups. Death rates were similar between the WPW group versus the control group (hazard ratio, 0.96; 95% confidence interval, 0.83-1.11; P=0.56). Nonablated WPW patients had a higher long-term death risk compared with ablated WPW patients (hazard ratio, 2.10; 95% confidence interval: 1.50-20.93; P<0.0001). Incident atrial fibrillation risk was higher in the WPW group compared with the control population (hazard ratio, 1.55; 95% confidence interval, 1.29-1.87; P<0.0001). Nonablated WPW patients had lower risk than ablated patients (hazard ratio, 0.39; 95% confidence interval, 0.28-0.53; P<0.0001). Long-term mortality rates in WPW patients are low and similar to an age-matched and gender-matched control population. WPW patients that underwent the multifactorial process of ablation had a lower mortality compared to nonablated WPW patients. Atrial fibrillation rates are high long-term, and ablation does not reduce this risk. © 2015 American Heart Association, Inc.

Long-term risk of seizures in adult survivors of sepsis.

Science.gov (United States)

Reznik, Michael E; Merkler, Alexander E; Mahta, Ali; Murthy, Santosh B; Claassen, Jan; Kamel, Hooman

2017-10-03

To examine the association between sepsis and the long-term risk of seizures. We conducted a retrospective population-based cohort study using administrative claims data from all emergency department visits and hospitalizations at nonfederal acute care hospitals in California, Florida, and New York from 2005 to 2013. Using previously validated diagnosis codes, we identified all adult patients hospitalized with sepsis. Our outcome was any emergency department visit or hospitalization for seizure. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). To confirm our findings, we used a matched cohort of hospitalized patients without sepsis for comparison and additionally assessed claims data from a nationally representative 5% sample of Medicare beneficiaries. We identified 842,735 patients with sepsis. The annual incidence of seizure was 1.29% (95% confidence interval [CI] 1.27%-1.30%) in patients with sepsis vs 0.16% (95% CI 0.16%-0.16%) in the general population (IRR 4.98; 95% CI 4.92-5.04). A secondary analysis using matched hospitalized patients confirmed these findings (IRR 4.33; 95% CI 4.13-4.55), as did a separate analysis of Medicare beneficiaries, in whom we found a similar strength of association (IRR 2.72; 95% CI 2.60-2.83), as we did in patients ≥65 years of age in our primary statewide data (IRR 2.83; 95% CI 2.78-2.88). We found that survivors of sepsis faced a significantly higher long-term risk of seizures than both the general population and other hospitalized patients. Our findings suggest that sepsis is associated with pathways that lead to permanent neurologic sequelae. © 2017 American Academy of Neurology.

Do depression, stress, sleep disruption, and inflammation alter hippocampal apoptosis and neurogenesis?

NARCIS (Netherlands)

Lucassen, P.J.; Meerlo, P.; Naylor, A.S.; van Dam, A.M.; Dayer, A.G.; Czeh, B.; Oomen, C.A.; Pariante, C.M.

2009-01-01

We discuss the regulation of cellular plasticity, focusing on neurogenesis and apoptosis in the adult hippocampus, by stress, sleep, inflammation, and depression. This is the fourth of five chapters in this book that present not only clinical data but also experimental evidence from animal models

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

Science.gov (United States)

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

2012-01-01

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

Predicting long-term graft survival in adult kidney transplant recipients

Directory of Open Access Journals (Sweden)

Brett W Pinsky

2012-01-01

Full Text Available The ability to accurately predict a population′s long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population′s long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS projections were calculated and com-pared with the population′s actual graft survival. The projection curves were created using a two-part estimation model that (1 fits a Kaplan-Meier survival curve immediately after transplant (Part A and (2 uses truncated observational data to model a survival function for long-term projection (Part B. Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted sur-vival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%. Excellent predictability (41.3% can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population′s long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.

Long-term consequences of adolescent cannabinoid exposure in adult psychopathology

Directory of Open Access Journals (Sweden)

Justine eRenard

2014-11-01

Full Text Available Marijuana is the most widely used illicit drug among adolescents and young adults. Unique cognitive, emotional, and social changes occur during this critical period of development from childhood into adulthood. The adolescent brain is in a state of transition and differs from the adult brain with respect to both anatomy (e.g., neuronal connections and morphology and neurochemistry (e.g., dopamine, GABA, and glutamate. These changes are thought to support the emergence of adult cerebral processes and behaviors. The endocannabinoid system plays an important role in development by acting on synaptic plasticity, neuronal cell proliferation, migration, and differentiation. Delta-9-tetrahydrocanabinol (THC, the principal psychoactive component in marijuana, acts as an agonist of the cannabinoid type 1 receptor (CB1R. Thus, over-activation of the endocannabinoid system by chronic exposure to CB1R agonists (e.g. THC, CP-55,940, and WIN55,212-2 during adolescence can dramatically alter brain maturation and cause long-lasting neurobiological changes that ultimately affect the function and behavior of the adult brain. Indeed, emerging evidence from both human and animal studies demonstrates that early-onset marijuana use has long-lasting consequences on cognition; moreover, in humans, this use is associated with a two-fold increase in the risk of developing a psychotic disorder. Here, we review the relationship between cannabinoid exposure during adolescence and the increased risk of neuropsychiatric disorders, focusing on both clinical and animal studies.

Physical activity enhances long-term quality of life in older adults: efficacy, esteem, and affective influences.

Science.gov (United States)

Elavsky, Steriani; McAuley, Edward; Motl, Robert W; Konopack, James F; Marquez, David X; Hu, Liang; Jerome, Gerald J; Diener, Ed

2005-10-01

Physical activity has been effective in enhancing quality of life (QOL) of older adults over relatively short periods of time. However, little is known about the long-term effects of physical activity and even less about the possible mediators of this relationship. We examined the mediating effects of psychological variables on the relationship between physical activity and global QOL (satisfaction with life) in older adults over a 4-year period. Participants (N = 174, M age = 66.7 years) completed a battery of psychosocial measures at 1 and 5 years following enrollment in a 6-month randomized controlled exercise trial. Panel analysis conducted within a covariance modeling framework indicated that physical activity was related to self-efficacy, physical self-esteem, and positive affect at 1 year, and in turn, greater levels of self-efficacy and positive affect were associated with higher levels of QOL. Analyses indicated that changes in physical activity over the 4-year period were related to increases in physical self-esteem and positive affect, but only positive affect directly influenced improvements in QOL. The findings lend support to the position that physical activity effects on QOL are in part mediated by intermediate psychological outcomes and that physical activity can have long-term effects on well-being.

Recommendations on Physical Activity and Exercise for Older Adults Living in Long-Term Care Facilities: A Taskforce Report.

Science.gov (United States)

de Souto Barreto, Philipe; Morley, John E; Chodzko-Zajko, Wojtek; H Pitkala, Kaisu; Weening-Djiksterhuis, Elizabeth; Rodriguez-Mañas, Leocadio; Barbagallo, Mario; Rosendahl, Erik; Sinclair, Alan; Landi, Francesco; Izquierdo, Mikel; Vellas, Bruno; Rolland, Yves

2016-05-01

A taskforce, under the auspices of The International Association of Gerontology and Geriatrics-Global Aging Research Network (IAGG-GARN) and the IAGG European Region Clinical Section, composed of experts from the fields of exercise science and geriatrics, met in Toulouse, in December 2015, with the aim of establishing recommendations of physical activity and exercise for older adults living in long-term care facilities (LTCFs). Due to the high heterogeneity in terms of functional ability and cognitive function that characterizes older adults living in LTCFs, taskforce members established 2 sets of recommendations: recommendations for reducing sedentary behaviors for all LTCF residents and recommendations for defining specific, evidence-based guidelines for exercise training for subgroups of LTCF residents. To promote a successful implementation of recommendations, taskforce experts highlighted the importance of promoting residents' motivation and pleasure, the key factors that can be increased when taking into account residents' desires, preferences, beliefs, and attitudes toward physical activity and exercise. The importance of organizational factors related to LTCFs and health care systems were recognized by the experts. In conclusion, this taskforce report proposes standards for the elaboration of strategies to increase physical activity as well as to prescribe exercise programs for older adults living in LTCFs. This report should be used as a guide for professionals working in LTCF settings. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

Legrand, Marie

2016-01-01

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

Self-reported competence in long term care provision for adult cancer survivors: A cross sectional survey of nursing and allied health care professionals.

Science.gov (United States)

Faithfull, S; Samuel, Carol; Lemanska, Agnieszka; Warnock, Clare; Greenfield, Diana

2016-01-01

Cancer survival is increasing as patients live longer with a cancer diagnosis. This success has implications for health service provision in that increasing numbers of adults who have received cancer therapy are requiring monitoring and long-term health care by a wide range of practitioners. Given these recent trends there is a need to explore staff perceptions and confidence in managing the consequences of cancer diagnosis and treatment in cancer survivors to enhance an integrated cancer service delivery. This study examines the self-reported perceptions of competence in nurses and professionals allied to medicine providing survivorship services caring for adults after cancer treatment in both secondary and primary care. A cross sectional survey of the adult cancer workforce using a self-assessment tool for assessing confidence in providing long-term cancer patient management. This study was a health service evaluation. The study was conducted within the United Kingdom. Respondents were 618 health care professionals of these 368 were specialist adult cancer nurses in oncology and the community setting and 250 cancer allied health professionals. The survey tool was developed with experts in cancer management, nurses professionals allied to medicine such as physiotherapists and dieticians, educationalists, patient groups as well as health service managers. Competence was assessed in 4 domains clinical practice, symptom management, care co-ordination and proactive management. Perceptions of training needs were also ascertained. Data were collected using an Internet survey distributed through cancer services, community settings and professional institutions. In total 618 practitioners who responded were providing services for adults' 1-year post cancer therapy. Practitioners felt confident in managing psychosocial care and communicating with patients. Deficits in self-reported confidence were found in long-term medications management, care planning, long-term and

Effect of long-term exposure to air pollution on anxiety and depression in adults: A cross-sectional study.

Science.gov (United States)

Vert, Cristina; Sánchez-Benavides, Gonzalo; Martínez, David; Gotsens, Xavier; Gramunt, Nina; Cirach, Marta; Molinuevo, José Luis; Sunyer, Jordi; Nieuwenhuijsen, Mark J; Crous-Bou, Marta; Gascon, Mireia

2017-08-01

The association between exposure to air pollutants and mental disorders among adults has been suggested, although results are not consistent. To analyze the association between long-term exposure to air pollution and history of anxiety and depression disorders and of medication use (benzodiazepines and antidepressants) in adults living in Barcelona. A total of 958 adults (45-74 years old) residents in Barcelona, most of them having at least one of their parents diagnosed with dementia (86%), and participating in the ALFA (Alzheimer and Families) study, were included. We used Land Use Regression (LUR) models to estimate long-term residential exposure (period 2009-2014) to PM 2.5 , PM 2.5 absorbance (PM 2.5 abs), PM 10 , PM coarse, NO 2 and NO x . Between 2013 and 2014 participants self-reported their history of anxiety and depression disorders and related medication use. The analysis was focused on those participants reporting outcome occurrence from 2009 onwards (until 2014). We observed an increased odds of history of depression disorders with increasing concentrations of all air pollutants [e.g. an increased odds of depression of 2.00 (95% CI; 1.37, 2.93) for each 10μg/m 3 NO 2 increase]. Such associations were consistent with an increased odds of medication use in relation to higher concentrations of air pollutants [e.g. an increased odds of antidepressants use of 1.23 (1.04, 1.44) for each 20μg/m 3 NO x increase]. Associations regarding anxiety disorders did not reach statistical significance. Our study shows that increasing long-term exposure to air pollution may increase the odds of depression and the use of antidepressants and benzodiazepines. Further studies are needed to replicate our results and confirm this association. Copyright © 2017 Elsevier GmbH. All rights reserved.

Putative Adult Neurogenesis in Old World Parrots: The Congo African Grey Parrot (Psittacus erithacus and Timneh Grey Parrot (Psittacus timneh

Directory of Open Access Journals (Sweden)

Pedzisai Mazengenya

2018-02-01

Full Text Available In the current study, we examined for the first time, the potential for adult neurogenesis throughout the brain of the Congo African grey parrot (Psittacus erithacus and Timneh grey parrot (Psittacus timneh using immunohistochemistry for the endogenous markers proliferating cell nuclear antigen (PCNA, which labels proliferating cells, and doublecortin (DCX, which stains immature and migrating neurons. A similar distribution of PCNA and DCX immunoreactivity was found throughout the brain of the Congo African grey and Timneh grey parrots, but minor differences were also observed. In both species of parrots, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, subventricular zone of the lateral wall of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and the rhombencephalon. The olfactory bulb and telencephalic subdivisions exhibited a higher density of both PCNA and DCX immunoreactive cells than any other brain region. DCX immunoreactive staining was stronger in the telencephalon than in the subtelencephalic structures. There was evidence of proliferative hot spots in the dorsal and ventral poles of the lateral ventricle in the Congo African grey parrots at rostral levels, whereas only the dorsal accumulation of proliferating cells was observed in the Timneh grey parrot. In most pallial regions the density of PCNA and DCX stained cells increased from rostral to caudal levels with the densest staining in the nidopallium caudolaterale (NCL. The widespread distribution of PCNA and DCX in the brains of both parrot species suggest the importance of adult neurogenesis and neuronal plasticity during learning and adaptation to external environmental variations.

Putative Adult Neurogenesis in Old World Parrots: The Congo African Grey Parrot (Psittacus erithacus) and Timneh Grey Parrot (Psittacus timneh).

Science.gov (United States)

Mazengenya, Pedzisai; Bhagwandin, Adhil; Manger, Paul R; Ihunwo, Amadi O

2018-01-01

In the current study, we examined for the first time, the potential for adult neurogenesis throughout the brain of the Congo African grey parrot ( Psittacus erithacus ) and Timneh grey parrot ( Psittacus timneh ) using immunohistochemistry for the endogenous markers proliferating cell nuclear antigen (PCNA), which labels proliferating cells, and doublecortin (DCX), which stains immature and migrating neurons. A similar distribution of PCNA and DCX immunoreactivity was found throughout the brain of the Congo African grey and Timneh grey parrots, but minor differences were also observed. In both species of parrots, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, subventricular zone of the lateral wall of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and the rhombencephalon. The olfactory bulb and telencephalic subdivisions exhibited a higher density of both PCNA and DCX immunoreactive cells than any other brain region. DCX immunoreactive staining was stronger in the telencephalon than in the subtelencephalic structures. There was evidence of proliferative hot spots in the dorsal and ventral poles of the lateral ventricle in the Congo African grey parrots at rostral levels, whereas only the dorsal accumulation of proliferating cells was observed in the Timneh grey parrot. In most pallial regions the density of PCNA and DCX stained cells increased from rostral to caudal levels with the densest staining in the nidopallium caudolaterale (NCL). The widespread distribution of PCNA and DCX in the brains of both parrot species suggest the importance of adult neurogenesis and neuronal plasticity during learning and adaptation to external environmental variations.

Transference and Countertransference Issues Unique to Long-Term Group Psychotherapy of Adult Women Molested as Children: Trials and Rewards.

Science.gov (United States)

Abney, Veronica D.; And Others

1992-01-01

Discusses transference and countertransference issues associated with long-term psychodynamic group treatment of adult women molested as children. Describes and examines these women's transference reactions toward group members and the therapist. Also explores the specific effects of race and ethnicity, sexual orientation, and gender of the…

Olfactory memory is enhanced in mice exposed to extremely low-frequency electromagnetic fields via Wnt/β-catenin dependent modulation of subventricular zone neurogenesis.

Science.gov (United States)

Mastrodonato, Alessia; Barbati, Saviana Antonella; Leone, Lucia; Colussi, Claudia; Gironi, Katia; Rinaudo, Marco; Piacentini, Roberto; Denny, Christine A; Grassi, Claudio

2018-01-10

Exposure to extremely low-frequency electromagnetic fields (ELFEF) influences the expression of key target genes controlling adult neurogenesis and modulates hippocampus-dependent memory. Here, we assayed whether ELFEF stimulation affects olfactory memory by modulating neurogenesis in the subventricular zone (SVZ) of the lateral ventricle, and investigated the underlying molecular mechanisms. We found that 30 days after the completion of an ELFEF stimulation protocol (1 mT; 50 Hz; 3.5 h/day for 12 days), mice showed enhanced olfactory memory and increased SVZ neurogenesis. These effects were associated with upregulated expression of mRNAs encoding for key regulators of adult neurogenesis and were mainly dependent on the activation of the Wnt pathway. Indeed, ELFEF stimulation increased Wnt3 mRNA expression and nuclear localization of its downstream target β-catenin. Conversely, inhibition of Wnt3 by Dkk-1 prevented ELFEF-induced upregulation of neurogenic genes and abolished ELFEF's effects on olfactory memory. Collectively, our findings suggest that ELFEF stimulation increases olfactory memory via enhanced Wnt/β-catenin signaling in the SVZ and point to ELFEF as a promising tool for enhancing SVZ neurogenesis and olfactory function.

Development of the adult neurogenic niche in the hippocampus of mice

Directory of Open Access Journals (Sweden)

Zeina eNicola

2015-05-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Effect of Low-Fat vs. Other Diet Interventions on Long-Term Weight Change in Adults: A Systematic Review and Meta-Analysis

OpenAIRE

Tobias, Deirdre K.; Chen, Mu; Manson, JoAnn E.; Ludwig, David S.; Willett, Walter; Hu, Frank B.

2015-01-01

Background: The effectiveness of low-fat diets for long-term weight loss has been debated for decades, with dozens of randomized trials (RCTs) and recent reviews giving mixed results. Methods: We conducted a random effects meta-analysis of RCTs to estimate the long-term effect of low-fat vs. higher fat dietary interventions on weight loss. Our search included RCTs conducted in adult populations reporting weight change outcomes at ≥1 year, comparing low-fat with higher fat interventions, publi...

The evidence for increased L1 activity in the site of human adult brain neurogenesis.

Directory of Open Access Journals (Sweden)

Alexey A Kurnosov

Full Text Available Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

Informing the Long-Term Learner Model: Motivating the Adult Learner (Phase 1)

Science.gov (United States)

2017-09-28

memory systems: 1) short - term memory , 2) working memory , and 3) long - term memory . The short - term memory stores the information for brief periods of...and the episodic buffer, which is linked to long - term memory . The visual working memory shares parts and interacts with attention (Gazzaley and...Nobre 2012; Zanto et al. 2011). Short - term memory is limited in its importance to

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

Directory of Open Access Journals (Sweden)

Maya Shakèd

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

Detrimental effects of physical inactivity on neurogenesis

Directory of Open Access Journals (Sweden)

Trenton Lippert

2016-01-01

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

Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

International Nuclear Information System (INIS)

Zou, Yani; Leu, David; Chui, Jennifer; Fike, John R.; Huang, Ting-Ting

2013-01-01

Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted

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

Science.gov (United States)

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

2011-05-19

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

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

Directory of Open Access Journals (Sweden)

Oberland Julia

2010-11-01

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

Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis

International Nuclear Information System (INIS)

Kim, Joong-Sun; Lee, Hae-June; Kim, Jong-Choon

2008-01-01

Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis. (author)

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

Science.gov (United States)

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

2004-09-22

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

What are the short-term and long-term effects of occupation-focused and occupation-based occupational therapy in the home on older adults' occupational performance?

DEFF Research Database (Denmark)

Nielsen, Tove Lise; Petersen, Kirsten Schultz; Nielsen, Claus Vinther

2016-01-01

critically appraised 13 of 995 detected papers. Extracted data were presented and summarised descriptively. Results Eight high-quality papers showed that occupation-focused and occupation-based occupational therapy using cognitive, behavioural and environmental strategies may significantly improve......Abstract Title What are the short-term and long-term effects of occupation-focused and occupation-based occupational therapy in the home on older adults’ occupational performance? A systematic review Background There is a lack of evidence-based knowledge about the effectiveness of home......-based occupational therapy for older adults aimed at improving occupational performance by practicing activities and tasks. Aim This review synthesizes and discusses evidence for the effectiveness of occupation-focused and occupation-based occupational therapy for older adults at home. Material and methods Peer...

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

Few long-term consequences after prolonged maternal separation in female Wistar rats.

Directory of Open Access Journals (Sweden)

Stina Lundberg

Full Text Available Environmental factors during the early-life period are known to have long-term consequences for the adult phenotype. An intimate interplay between genes and environment shape the individual and may affect vulnerability for psychopathology in a sex-dependent manner. A rodent maternal separation model was here used to study the long-term effects of different early-life rearing conditions on adult behavior, HPA axis activity and long-term voluntary alcohol intake in female rats. Litters were subjected to 15 min (MS15 or 360 min (MS360 of daily maternal separation during postnatal day 1-21. In adulthood, the behavioral profiles were investigated using the multivariate concentric square field™ (MCSF test or examined for HPA axis reactivity by cat-odor exposure with subsequent characterization of voluntary alcohol intake and associated changes in HPA axis activity. Adult female MS360 offspring showed mostly no, or only minor, effects on behavior, HPA axis reactivity and long-term alcohol intake relative to MS15. Instead, more pronounced effects were found dependent on changes in the natural hormonal cycle or by the choice of animal supplier. However, changes were revealed in corticosterone load after long-term alcohol access, as females subjected to MS360 had higher concentrations of fecal corticosterone. The present findings are in line with and expand on previous studies on the long-term effects of maternal separation in female rats with regard to behavior, HPA axis activity and voluntary alcohol intake. It can also be a window into further studies detailing how early-life experiences interact with other risk and protective factors to impact the adult phenotype and how possible sex differences play a role.

Stage-specific functions of the small Rho GTPases Cdc42 and Rac1 for adult hippocampal neurogenesis

DEFF Research Database (Denmark)

Vadodaria, Krishna C; Brakebusch, Cord; Suter, Ueli

2013-01-01

The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC......) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation......, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases...

Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences.

Science.gov (United States)

Donzis, Elissa J; Tronson, Natalie C

2014-11-01

This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-term complications of splenectomy in adult immune thrombocytopenia.

Science.gov (United States)

Thai, Lan-Huong; Mahévas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Dumas, Guillaume; Khellaf, Mehdi; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

2016-11-01

The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5-528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 [95% confidence interval: 1.13-14.21]). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP.

Long-term Outcome of Arterial Stroke in Children

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2015-05-01

Full Text Available Investigators at University Children’s Hospital, Inselspital, and Universities of Bern, Geneva, Basel, and Zurich, Switzerland compared long-term outcome of children (1 month-16 years and young adults (16.1-45 years with arterial ischemic stroke (AIS using prospective data from the Swiss Neuropediatric Stroke Registry and the Adult Bernese stroke registry, between Jan 2000 and Dec 2008.

Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt : Does the beneficial effect persist?

NARCIS (Netherlands)

van Loon, Rosa Laura E.; Hoendermis, Elke S.; Duffels, Marielle G. J.; Vonk-Noordegraaf, Anton; Mulder, Barbara J. M.; Hillege, Hans L.; Berger, Rolf M. F.

2007-01-01

BACKGROUND: Data on long-term response to bosentan in adults and especially children with pulmonary arterial hypertension (PAH) associated with systemic-to-pulmonary shunt are scarce. METHODS: We studied bosentan efficacy in 30 patients (20 adults, 10 children) with the disease at short- (4 months),

Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: Does the beneficial effect persist?

NARCIS (Netherlands)

van Loon, Rosa Laura E.; Hoendermis, Elke S.; Duffels, Marielle G. J.; Vonk-Noordegraaf, Anton; Mulder, Barbara J. M.; Hillege, Hans L.; Berger, Rolf M. F.

2007-01-01

Background Data on long-term response to bosentan in adults and especially children with pulmonary arterial hypertension (PAH) associated with systemic-to-pulmonary shunt are scarce. Methods We studied bosentan efficacy in 30 patients (20 adults, 10 children) with the disease at short- (4 months),

Treatment outcome and long-term stability of skeletal changes following maxillary distraction in adult subjects of cleft lip and palate

OpenAIRE

Satinder Pal Singh; Ashok Kumar Jena; Vidya Rattan; Ashok Kumar Utreja

2012-01-01

Aim : To evaluate the treatment outcome and long-term stability of skeletal changes following maxillary advancement with distraction osteogenesis in adult subjects of cleft lip and palate. Materials and Methods: Total 12 North Indian adult patients in the age range of 17-34 years with cleft lip and palate underwent advancement of maxilla by distraction osteogenesis. Lateral cephalograms recorded prior to distraction, at the end of distraction, 6 months after distraction, and at least 24 month...

Intermediate-term and long-term mortality among acute medical patients hospitalized with community-acquired sepsis

DEFF Research Database (Denmark)

Henriksen, Daniel P; Pottegård, Anton; Laursen, Christian B

2017-01-01

OBJECTIVE: Admission with severe sepsis is associated with an increased short-term mortality, but it is unestablished whether sepsis severity has an impact on intermediate-term and long-term mortality following admission to an acute medical admission unit. PATIENTS AND METHODS: This was a populat......OBJECTIVE: Admission with severe sepsis is associated with an increased short-term mortality, but it is unestablished whether sepsis severity has an impact on intermediate-term and long-term mortality following admission to an acute medical admission unit. PATIENTS AND METHODS......: This was a population-based study of all adults admitted to an acute medical admission unit, Odense University Hospital, Denmark, from September 2010 to August 2011, identified by symptoms and clinical findings. We categorized the mortality periods into intermediate-term (31-180 days) and long-term (181-365, 366...

Ramipril mitigates radiation-induced impairment of neurogenesis in the rat dentate gyrus

International Nuclear Information System (INIS)

Jenrow, Kenneth A; Brown, Stephen L; Liu, Jianguo; Kolozsvary, Andrew; Lapanowski, Karen; Kim, Jae Ho

2010-01-01

Sublethal doses of whole brain irradiation (WBI) are commonly administered therapeutically and frequently result in late delayed radiation injuries, manifesting as severe and irreversible cognitive impairment. Neural progenitors within the subgranular zone (SGZ) of the dentate gyrus are among the most radiosensitive cell types in the adult brain and are known to participate in hippocampal plasticity and normal cognitive function. These progenitors and the specialized SZG microenvironment required for neuronal differentiation are the source of neurogenic potential in the adult dentate gyrus, and provide a continuous supply of immature neurons which may then migrate into the adjacent granule cell layer to become mature granule cell neurons. The extreme radiosensitivity of these progenitors and the SGZ microenvironment suggests the hippocampus as a prime target for radiation-induced cognitive impairment. The brain renin-angiotensin system (RAS) has previously been implicated as a potent modulator of neurogenesis within the SGZ and selective RAS inhibitors have been implicated as mitigators of radiation brain injury. Here we investigate the angiotensin converting enzyme (ACE) inhibitor, ramipril, as a mitigator of radiation injury in this context. Adult male Fisher 344 rats received WBI at doses of 10 Gy and 15 Gy. Ramipril was administered beginning 24 hours post-WBI and maintained continuously for 12 weeks. Ramipril produced small but significant reductions in the deleterious effects of radiation on progenitor proliferation and neuronal differentiation in the rat dentate gyrus following 10 Gy-WBI, but was not effective following 15 Gy-WBI. Ramipril also reduced the basal rate of neurogenesis within the SGZ in unirradiated control rats. Our results indicate that chronic ACE inhibition with ramipril, initiated 24 hours post-irradiation, may reduce apoptosis among SGZ progenitors and/or inflammatory disruption of neurogenic signaling within SGZ microenvironment, and

Long-Term Changes in the Distributions of Larval and Adult Fish in the Northeast U.S. Shelf Ecosystem.

Directory of Open Access Journals (Sweden)

Harvey J Walsh

Full Text Available Many studies have documented long-term changes in adult marine fish distributions and linked these changes to climate change and multi-decadal climate variability. Most marine fish, however, have complex life histories with morphologically distinct stages, which use different habitats. Shifts in distribution of one stage may affect the connectivity between life stages and thereby impact population processes including spawning and recruitment. Specifically, many marine fish species have a planktonic larval stage, which lasts from weeks to months. We compared the spatial distribution and seasonal occurrence of larval fish in the Northeast U.S. Shelf Ecosystem to test whether spatial and temporal distributions changed between two decades. Two large-scale ichthyoplankton programs sampled using similar methods and spatial domain each decade. Adult distributions from a long-term bottom trawl survey over the same time period and spatial area were also analyzed using the same analytical framework to compare changes in larval and adult distributions between the two decades. Changes in spatial distribution of larvae occurred for 43% of taxa, with shifts predominately northward (i.e., along-shelf. Timing of larval occurrence shifted for 49% of the larval taxa, with shifts evenly split between occurring earlier and later in the season. Where both larvae and adults of the same species were analyzed, 48% exhibited different shifts between larval and adult stages. Overall, these results demonstrate that larval fish distributions are changing in the ecosystem. The spatial changes are largely consistent with expectations from a changing climate. The temporal changes are more complex, indicating we need a better understanding of reproductive timing of fishes in the ecosystem. These changes may impact population productivity through changes in life history connectivity and recruitment, and add to the accumulating evidence for changes in the Northeast U.S. Shelf

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

Science.gov (United States)

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

2017-07-01

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

Adult neurogenesis is reduced in the dorsal hippocampus of rats displaying learned helplessness behavior.

Science.gov (United States)

Ho, Y C; Wang, S

2010-11-24

Clinical and preclinical studies suggest that the hippocampus has a role in the pathophysiology of major depression. In the learned helplessness (LH) animal model of depression after inescapable shocks (ISs) animals that display LH behavior have reduced cell proliferation in the hippocampus; this effect can be reversed by antidepressant treatment. Using this model, we compared rats that displayed LH behavior and rats that did not show LH behavior (NoLH) after ISs to determine whether reduced hippocampal cell proliferation is associated with the manifestation of LH behavior or is a general response to stress. Specifically, we examined cell proliferation, neurogenesis, and synaptic function in dorsal and ventral hippocampus of LH and NoLH animals and control rats that were not shocked. The LH rats had showed reduced cell proliferation, neurogenesis, and synaptic transmission in the dorsal hippocampus, whereas no changes were seen in the ventral hippocampus. These changes were not observed in the NoLH animals. In a group of NoLH rats that received the same amount of electrical shock as the LH rats to control for the unequal shocks received in these two groups, we observed changes in Ki-67(+) cells associated with acute stress. We conclude that reduced hippocampal cell proliferation and neurogenesis are associated with the manifestation of LH behavior and that the dorsal hippocampus is the most affected area. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Serum insulin-like growth factor-I (IGF-I) levels during long-term IGF-I treatment of children and adults with primary GH resistance (Laron syndrome).

Science.gov (United States)

Laron, Z; Klinger, B; Silbergeld, A

1999-01-01

Serum IGF-I levels were measured in 14 patients (9 children and 5 adults) with Laron syndrome (LS) during long-term treatment by IGF-I. Recombinant IGF-I (FK-780, Fujisawa Pharmaceutical Co. Ltd., Japan) was administered once daily subcutaneously before breakfast for 3-5 years to the children and for 9 months to the adults. The initial daily dose was 150 micrograms/kg for children and 120 micrograms/kg for adults. Before initiation of treatment the mean overnight fasting levels of serum IGF-I in the children was 3.2 +/- 0.8 nmol/l (mean +/- SEM), rising to 10 +/- 1.7 nmol/l during long-term treatment even on a dose of 120 micrograms/kg/day. The serum IGF-I levels 4 hours after injection rose from 31.2 +/- 3.5 to 48 +/- 2 nmol/l. In the adult patients, the initial basal IGF-I was 4.1 +/- 0.7 nmol/l, rising to 16.1 +/- 3.84 nmol/l after 8-9 months treatment. Serum IGF-I levels at 4 hours after injection rose in the adult patients from 24.1 +/- 5.8 up to 66.8 +/- 15.4 nmol/l. A progressively increasing half-life during long term exogenous administration of IGF-I to patients with Laron syndrome was demonstrated by following serum IGF-I dynamics after injection. Based on the fact that no antibodies to IGF-I were detected and on findings in previous studies, it is speculated that the increasing serum IGF-I levels during long-term IGF-I treatment are caused by an increase in serum IGFBP-3 induced by chronic IGF-I administration. It is concluded that treatment with IGF-I necessitates regular monitoring of serum IGF-I levels; in patients in whom the age adjusted maximal levels are exceeded, a reduction of the daily IGF-I dose is indicated to avoid undesirable effects.

Comprehensive long-term management program for asthma: effect on outcomes in adult African-Americans.

Science.gov (United States)

Kelso, T M; Abou-Shala, N; Heilker, G M; Arheart, K L; Portner, T S; Self, T H

1996-06-01

To determine if a comprehensive long-term management program, emphasizing inhaled corticosteroids and patient education, would improve outcomes in adult African-American asthmatics a nonrandomized control trial with a 2-year intervention was performed in a university-based clinic. Inclusion criteria consisted of (> or = 5) emergency department (ED) visits or hospitalizations (> or = 2) during the previous 2 years. Intervention patients were volunteers; a comparable control group was identified via chart review at hospitals within the same area and time period as the intervention patients. Individualized doses of beclomethasone with a spacer, inhaled albuterol "as needed," and crisis prednisone were the primary therapies. Environmental control, peak flow monitoring, and a partnership with the patient were emphasized. Detailed patient education was an integral part of management. Control patients received usual care from local physicians. ED visits and hospitalizations for 2 years before and 2 years during the intervention period were compared. Quality of life (QOL) measurements were made at baseline and every 6 months in the intervention group. Study group (n = 21) had a significant reduction in ED visits (2.3 +/- 0.2 pre-intervention versus 0.6 +/- 0.2 post-intervention; P = 0.0001). Control group (n = 18) did not have a significant change in ED visits during the 2-year post-intervention period (2.6 +/- 0.2 pre-intervention versus 2.0 +/- 0.2 post-intervention; P = 0.11). Both groups had significant reductions in hospitalizations, but the study group had a greater reduction. Sixty-two percent of study patients had complete elimination of ED visits and hospitalizations, whereas no control patients had total elimination of the need for institutional acute care. QOL in the study patients revealed significant improvements for most parameters. A comprehensive long-term management program emphasizing inhaled corticosteroids combined with other state-of-the-art management

Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors

Directory of Open Access Journals (Sweden)

Jasmine Kolb

2018-04-01

Full Text Available Summary: Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on the activity of intrinsic neurogenic transcription factors remain poorly defined. Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is subject to posttranslational regulation in the SVZ olfactory bulb neurogenic system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells follows downregulation of EGFR signaling and is modulated by methylation of MEIS2 on a conserved arginine, which lies in close proximity to nested binding sites for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1. Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal differentiation. Our results describe a form of posttranscriptional modulation of adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis through posttranslational modification of a transcriptional regulator of cell fate. : A hallmark of adult neurogenesis is its strong dependence on physiological stimuli and environmental signals. Schulte and colleagues show that the nuclear localization and activity of a transcriptional regulator of adult neurogenesis is controlled by posttranslational modification. Their results link intrinsic control over neuron production to external signals and help to explain how adult neurogenesis can occur “on demand.” Keywords: subventricular zone, stem cell niche, posttranslational modification, controlled nuclear import, TALE-homdomain protein, MEIS2, PBX1, CRM1, neurogenesis, stem cell niche

A Long-Term Outcome Study of Selective Mutism in Childhood

Science.gov (United States)

Steinhausen, Hans-Christoph; Wachter, Miriam; Laimbock, Karin; Metzke, Christa Winkler

2006-01-01

Objective: Controlled study of the long-term outcome of selective mutism (SM) in childhood. Method: A sample of 33 young adults with SM in childhood and two age- and gender-matched comparison groups were studied. The latter comprised 26 young adults with anxiety disorders in childhood (ANX) and 30 young adults with no psychiatric disorders during…

Long-term follow-up of reflux nephropathy in adults with vesicoureteral reflux - radiological and pathoanatomical analysis

International Nuclear Information System (INIS)

Koehler, J.; Thysell, H.; Tencer, J.; Forsberg, L.; Hellstroem, M.

2001-01-01

Purpose: To study the long-term development of urographic renal morphology in adults with vesicoureteral reflux, to investigate the relationship between renal damage and reflux grade, and to analyse the association between the long-term urographic outcome and the occurrence of acute pyelonephritis and reflux during follow-up. The purpose was also to try to distinguish between acquired and developmental renal damage, based on analyses of renal histological specimens and urographic features, and to analyse associated congenital urogenital abnormalities and family history of reflux, reflux nephropathy, urological malformation or death from end-stage renal disease. Material and Methods: Renal damage was identified in 100 (83 women) of 115 adults, selected because of documented reflux. Eighty-seven patients had two urographies done (median interval 14.3 years). The extent and progression of renal damage were assessed and features of developmental renal damage were determined. Histological renal specimens were available in 23 patients with renal damage. Results and Conclusions: The extent of renal damage correlated positively with the severity of reflux. No renal damage developed during the follow-up in 45 previously undamaged kidneys and progression of renal damage was rare (4 of 120 previously damaged kidneys), despite persisting reflux in half of the cases and episodes of acute pyelonephritis during follow-up. Thus, repeated renal imaging is rarely justified in adults with reflux nephropathy. Histological examination showed 'chronic pyelonephritis' in all 23 cases and co-existing renal dysplasia in 1 case. The detailed urographic analysis did not reveal support for developmental renal damage. High frequencies of associated congenital urogenital abnormalities and of a positive family history were found. Thus, congenital and/or hereditary factors cannot be discarded as background factors for the development of renal damage

A Conditioning Analysis of Infant Long-Term Memory.

Science.gov (United States)

Sullivan, Margaret W.; And Others

1979-01-01

Assesses the long-term retention of conditioned operant footkicks by three-month-old infants. Views a conditioning analysis as a logical means by which to bridge the gap between animal and adult human models of memory. (Author/RH)

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

Science.gov (United States)

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

2017-01-01

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

Treatment outcome and long-term stability of skeletal changes following maxillary distraction in adult subjects of cleft lip and palate.

Science.gov (United States)

Singh, Satinder Pal; Jena, Ashok Kumar; Rattan, Vidya; Utreja, Ashok Kumar

2012-04-01

To evaluate the treatment outcome and long-term stability of skeletal changes following maxillary advancement with distraction osteogenesis in adult subjects of cleft lip and palate. Total 12 North Indian adult patients in the age range of 17-34 years with cleft lip and palate underwent advancement of maxilla by distraction osteogenesis. Lateral cephalograms recorded prior to distraction, at the end of distraction, 6 months after distraction, and at least 24 months (mean 25.5 ± 1.94 months) after distraction osteogenesis were used for the evaluation of treatment outcome and long-term stability of the skeletal changes. Descriptive analysis, ANOVA, and post-hoc test were used, and P-value 0.05 was considered as a statistically significant level. Maxillary distraction resulted in significant advancement of maxilla (Pmaxillary distraction. The position of the mandible and facial heights were stable during distraction. During the first 6 months of the post-distraction period, the maxilla showed relapse of approximately 30%. However, after 6 months post distraction, the relapse was very negligible. Successful advancement of maxilla was achieved by distraction osteogenesis in adult subjects with cleft lip and palate. Most of the relapse occurred during the first 6 months of post-distraction period, and after that the outcomes were stable.

Animal-Assisted Therapy and Application to Older Adults in Long Term Care

Directory of Open Access Journals (Sweden)

Kimberly Ann Mercer

2015-05-01

Full Text Available In the past thirty years animal-assisted therapy (AAT has moved beyond anecdotal status to a scientific evidence-based intervention. AAT comes in many shapes and sizes. There are a variety of animals which can be used such as dogs, cats, rabbits, horses, guinea pigs, goats, dolphins, and even fish aquariums. Loneliness is a common theme among older adults in long term care (LTC. Many older adults living in LTC facilities feel isolated. Some have little contact with family members or friends. Many describe feelings of loneliness and withdraw from social activities and interaction with others. Some feel as if they have nothing to look forward to and find no useful purpose in life.  The absence of having another to care for or nurture can also be distressing. The purpose of this project was to explore the use of AAT as an intervention to decrease loneliness in residents living in a LTC setting by introducing visits from a Sphynx cat registered by the Delta Society as a therapy animal. The project sample consisted of seven participants all over the age of 60 years who resided in a LTC facility in Texas. Pre-intervention and post-intervention checklists and open-ended questions were employed to collect data from participants. Analysis of the project findings revealed a notable decrease in loneliness.

Direct and indirect effects of nutritional status, physical function and cognitive function on activities of daily living in Japanese older adults requiring long-term care.

Science.gov (United States)

Kamo, Tomohiko; Nishida, Yuusuke

2014-10-01

To identify the direct and indirect effects of nutritional status, physical function, and cognitive function on activities of daily living in Japanese older adults requiring long-term care. In total, 179 participants aged ≥ 65 years who were eligible for long-term care insurance (mean age 85.5 ± 7.8 years) were recruited for this study. Nutritional status (Mini Nutritional Assessment, Short Form) and physical function (Short Physical Performance Battery) were examined. Activities of daily living, cognitive function and frailty were assessed using the Barthel Index, Mini-Mental State Examination and Clinical Frailty Scale, respectively. Path analysis was used to determine relationships between these factors and the activities of daily living. For Japanese older adults requiring long-term care, pathways were modeled for nutritional status, physical function and the activities of daily living. The total effect of nutritional status was 0.516 (Pphysical function on the activities of daily living was 0.458 (Pphysical function in aged Japanese people requiring long-term care. These findings suggest that maintaining good nutritional status and nutritional support might delay physical function decline, and prolong the activities of daily living. © 2013 Japan Geriatrics Society.

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

Science.gov (United States)

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

2016-12-01

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

Increased radial glia quiescence, decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon.

Science.gov (United States)

Edelmann, Kathrin; Glashauser, Lena; Sprungala, Susanne; Hesl, Birgit; Fritschle, Maike; Ninkovic, Jovica; Godinho, Leanne; Chapouton, Prisca

2013-09-01

The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia. Copyright © 2013 Wiley Periodicals, Inc.

Human Adult Stem Cells Maintain a Constant Phenotype Profile Irrespective of Their Origin, Basal Media, and Long Term Cultures

Directory of Open Access Journals (Sweden)

Indumathi Somasundaram

2015-01-01

Full Text Available The study aims to identify the phenotypic marker expressions of different human adult stem cells derived from, namely, bone marrow, subcutaneous fat, and omentum fat, cultured in different media, namely, DMEM-Low Glucose, Alpha-MEM, DMEM-F12 and DMEM-KO and under long term culture conditions (>P20. We characterized immunophenotype by using various hematopoietic, mesenchymal, endothelial markers, and cell adhesion molecules in the long term cultures (Passages-P1, P3, P5, P9, P12, P15, and P20. Interestingly, data revealed similar marker expression profiles irrespective of source, basal media, and extensive culturing. This demonstrates that all adult stem cell sources mentioned in this study share similar phenotypic marker and all media seem appropriate for culturing these sources. However, a disparity was observed in the markers such as CD49d, CD54, CD117, CD29, and CD106, thereby warranting further research on these markers. Besides the aforesaid objective, it is understood from the study that immunophenotyping acts as a valuable tool to identify inherent property of each cell, thereby leading to a valuable cell based therapy.

Alterations in Brain Inflammation, Synaptic Proteins, and Adult Hippocampal Neurogenesis during Epileptogenesis in Mice Lacking Synapsin2.

Directory of Open Access Journals (Sweden)

Deepti Chugh

Full Text Available Synapsins are pre-synaptic vesicle-associated proteins linked to the pathogenesis of epilepsy through genetic association studies in humans. Deletion of synapsins causes an excitatory/inhibitory imbalance, exemplified by the epileptic phenotype of synapsin knockout mice. These mice develop handling-induced tonic-clonic seizures starting at the age of about 3 months. Hence, they provide an opportunity to study epileptogenic alterations in a temporally controlled manner. Here, we evaluated brain inflammation, synaptic protein expression, and adult hippocampal neurogenesis in the epileptogenic (1 and 2 months of age and tonic-clonic (3.5-4 months phase of synapsin 2 knockout mice using immunohistochemical and biochemical assays. In the epileptogenic phase, region-specific microglial activation was evident, accompanied by an increase in the chemokine receptor CX3CR1, interleukin-6, and tumor necrosis factor-α, and a decrease in chemokine keratinocyte chemoattractant/ growth-related oncogene. Both post-synaptic density-95 and gephyrin, scaffolding proteins at excitatory and inhibitory synapses, respectively, showed a significant up-regulation primarily in the cortex. Furthermore, we observed an increase in the inhibitory adhesion molecules neuroligin-2 and neurofascin and potassium chloride co-transporter KCC2. Decreased expression of γ-aminobutyric acid receptor-δ subunit and cholecystokinin was also evident. Surprisingly, hippocampal neurogenesis was reduced in the epileptogenic phase. Taken together, we report molecular alterations in brain inflammation and excitatory/inhibitory balance that could serve as potential targets for therapeutics and diagnostic biomarkers. In addition, the regional differences in brain inflammation and synaptic protein expression indicate an epileptogenic zone from where the generalized seizures in synapsin 2 knockout mice may be initiated or spread.

Long-term selenium status in humans

International Nuclear Information System (INIS)

Baskett, C.K.; Spate, V.L.; Mason, M.M.; Nichols, T.A.; Williams, A.; Dubman, I.M.; Gudino, A.; Denison, J.; Morris, J.S.

2001-01-01

The association of sub-optimal selenium status with increased risk factors for some cancers has been reported in two recent epidemiological studies. In both studies the same threshold in selenium status was observed, below which, cancer incidence increased. To assess the use of nails as a biologic monitor to measure the long-term selenium status, an eight-year longitudinal study was undertaken with a group of 11 adult subjects, 5 women and 6 men. Selenium has been measured by instrumental neutron activation analysis. Differences between fingernails and toenails with be discussed. In addition, the results will be discussed in the context of the long-term stability of the nail monitor to measure selenium status during those periods when selenium determinants are static; and the changes that occur as a result of selenium supplementation. (author)

Plasticity of hippocampal stem/progenitor cells to enhance neurogenesis in response to kainate-induced injury is lost by middle age

OpenAIRE

Hattiangady, Bharathi; Rao, Muddanna S.; Shetty, Ashok K.

2008-01-01

A remarkable up-regulation of neurogenesis through increased proliferation of neural stem/progenitor cells (NSCs) is a well-known plasticity displayed by the young dentate gyrus (DG) following brain injury. To ascertain whether this plasticity is preserved during aging, we quantified DG neurogenesis in the young adult, middle-aged and aged F344 rats after kainic acid induced hippocampal injury. Measurement of new cells that are added to the dentate granule cell layer (GCL) between post-injury...

Predictors of long-term smoking cessation: results from the global adult tobacco survey in Poland (2009–2010

Directory of Open Access Journals (Sweden)

Kaleta Dorota

2012-11-01

Full Text Available Abstract Background Expanding the information on determinants of smoking cessation is crucial for developing and implementing more effective tobacco control measures at the national as well as European levels. Data on smoking cessation and its social correlates among adults from middle-income countries of Central and Eastern Europe are still poorly reported in the literature. The aim of the study was to analyze the association of socio-demographic indicators with long term tobacco smoking cessation (quit smoking for at least one year prior to interview among adults. Moreover, we evaluated motives for giving up smoking from former smokers. Methods Data on former as well as current smokers’ socio-demographic and smoking-related characteristics were derived from the Global Adult Tobacco Survey (GATS. GATS is a cross-sectional, nationally representative household survey implemented in Poland between 2009 and 2010. GATS collected data on a representative sample of 7,840 individuals including 1,206 individuals who met the criteria of long-term smoking cessation and 2,233 current smokers. Smoking cessation rate was calculated as the number of former smokers divided by the number of ever smokers. Logistic regression analyses were used to obtain odds ratios (ORs and 95% confidence interval (CI of the broad number of variables on successful cessation of smoking. Results Among females the quit rate was 30.4% compared to 37.9% in males (p  Conclusion Results indicated that smoking cessation policies focused on younger age groups are vital for curbing tobacco epidemic in Poland and should become a public health main concern. There is also the need for interventions to raise awareness on smoking health risks and quitting benefits are crucial to increase cessation potential among adult smokers. Nevertheless further effort needs to be done to prevent smoking uptake.

Long-Term Effects of a Screening Intervention for Depression on Suicide Rates among Japanese Community-Dwelling Older Adults.

Science.gov (United States)

Oyama, Hirofumi; Sakashita, Tomoe

2016-04-01

To explore the long-term impact of a universal screening intervention for depression on suicide rates among older community-dwelling adults, with gender as an effect modifier. Controlled cohort study reporting long-term follow-up of previous research. Two sets of three municipalities in Japan were assigned as intervention and control regions and compared with the surrounding zone and prefecture. Intervention area residents aged 60 years and older (14,291) were invited to participate in a 2-year intervention (2005-2006). Four population-based dynamic cohorts of residents aged 65 years and older (1999-2010) were included as subjects, 6 years before and after the intervention started. At-risk residents within the intervention region (4,918) were invited for a two-step screening program; 2,552 participated in the program linked with care/support services for 2 years. An education program open to the public was held. Changes in suicide from a 6-year baseline to the 2-year intervention and a 4-year follow-up in the intervention region (11,700 adults ≥65 years) were compared with a matched control and two comparison areas using mixed-effects negative binomial regression models. Suicide rates among older adults exposed to screening were compared with those of the control region. Suicide rates in the intervention region decreased by 48%, which was significantly greater than in the three comparison areas. The program's benefits lasted longer for women than men. Screening exposure may be associated with decreased suicide risk over the 4-year follow-up. Universal screening may decrease suicide rates among older adults, with potential gender differences in treatment response. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Dexamethasone and Long-Term Outcome of Tuberculous Meningitis in Vietnamese Adults and Adolescents

Science.gov (United States)

Török, M. Estée; Bang, Nguyen Duc; Chau, Tran Thi Hong; Yen, Nguyen Thi Bich; Thwaites, Guy E.; Thi Quy, Hoang; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Thi Thanh Hoang, Hoang; Wolbers, Marcel; Farrar, Jeremy J.

2011-01-01

Background Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown. Methods Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability. Results 545 patients were randomised to receive either dexamethasone (274 patients) or placebo (271 patients). 50 patients (9.2%) were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07) but five-year survival rates were similar (0.54 versus 0.51, p = 0.51) in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07) but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36). The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7%) and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32). Conclusions Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM. Trial Registration ClinicalTrials.gov NCT01317654 NCT01317654?term = tuberculous+meningitis&rank = 3 PMID:22174748

Long-term care financing: lessons from France.

Science.gov (United States)

Doty, Pamela; Nadash, Pamela; Racco, Nathalie

2015-06-01

POLICY POINTS: France's model of third-party coverage for long-term services and supports (LTSS) combines a steeply income-adjusted universal public program for people 60 or older with voluntary supplemental private insurance. French and US policies differ: the former pay cash; premiums are lower; and take-up rates are higher, in part because employer sponsorship, with and without subsidization, is more common-but also because coverage targets higher levels of need and pays a smaller proportion of costs. Such inexpensive, bare-bones private coverage, especially if marketed as a supplement to a limited public benefit, would be more affordable to those Americans currently most at risk of "spending down" to Medicaid. An aging population leads to a growing demand for long-term services and supports (LTSS). In 2002, France introduced universal, income-adjusted, public long-term care coverage for adults 60 and older, whereas the United States funds means-tested benefits only. Both countries have private long-term care insurance (LTCI) markets: American policies create alternatives to out-of-pocket spending and protect purchasers from relying on Medicaid. Sales, however, have stagnated, and the market's viability is uncertain. In France, private LTCI supplements public coverage, and sales are growing, although its potential to alleviate the long-term care financing problem is unclear. We explore whether France's very different approach to structuring public and private financing for long-term care could inform the United States' long-term care financing reform efforts. We consulted insurance experts and conducted a detailed review of public reports, academic studies, and other documents to understand the public and private LTCI systems in France, their advantages and disadvantages, and the factors affecting their development. France provides universal public coverage for paid assistance with functional dependency for people 60 and older. Benefits are steeply income

Health-Related Quality of Life: Expanding a Conceptual Framework to Include Older Adults Who Receive Long-Term Services and Supports

Science.gov (United States)

Zubritsky, Cynthia; Abbott, Katherine M.; Hirschman, Karen B.; Bowles, Kathryn H.; Foust, Janice B.; Naylor, Mary D.

2013-01-01

For older adults receiving long-term services and supports (LTSS), health-related quality of life (HRQoL) has emerged as a critical construct to examine because of its focus on components of well-being, which are affected by progressive changes in health status, health care, and social support. HRQoL is a health-focused quality of life (QOL)…

Health-related quality of life of young adults with Turner syndrome following a long-term randomized controlled trial of recombinant human growth hormone

Directory of Open Access Journals (Sweden)

Van Vliet Guy

2011-05-01

Full Text Available Abstract Background There are limited long-term randomized controlled trials of growth hormone (GH supplementation to adult height and few published reports of the health-related quality of life (HRQOL following treatment. The present follow-up study of young adults from a long-term controlled trial of GH treatment in patients with Turner syndrome (TS yielded data to examine whether GH supplementation resulted in a higher HRQOL (either due to taller stature or from the knowledge that active treatment and not placebo had been received or alternatively a lower HRQOL (due to medicalization from years of injections. Methods The original trial randomized 154 Canadian girls with TS aged 7-13 years from 13 centres to receive either long-term GH injections at the pharmacologic dose of 0.3 mg/kg/week or to receive no injections; estrogen prescription for induction of puberty was standardized. Patients were eligible for the follow-up study if they were at least 16 years old at the time of follow-up. The instrument used to study HRQOL was the SF-36, summarized into physical and mental component scales (PCS and MCS; higher scores indicate better HRQOL. Results Thirty-four of the 48 eligible participants (71% consented to participate; data were missing for one patient. Both groups (GH and no treatment had normal HRQOL at this post-treatment assessment. The GH group had a (mean ± SD PCS score of 56 ± 5; the untreated group 58 ± 4; mean score for 16-24 year old females in the general population 53.5 ± 6.9. The GH group had a mean MCS score of 52 ± 6; the untreated group 49 ± 13; mean score for 16-24 year old females in the general population 49.6 ± 9.8. Secondary analyses showed no relationship between HRQOL and height. Conclusions We found no benefit or adverse effect on HRQOL either from receiving or not receiving growth hormone injections in a long-term randomized controlled trial, confirming larger observational studies. We suggest that it remains

Autonomy and Acceptance of Long-Term Care

Science.gov (United States)

Hsu, Hui-Chuan; Ting, Yu-Shan; Jiang, Ting-Wen; Chien, Ming-Chih; Chien, Chih-Hsin

2009-01-01

This study explored the relationship between four types of autonomy (health autonomy, informational autonomy, living autonomy, and financial autonomy) and the acceptance of five types of long-term care (adult day care, respite care, assisted living, unit care, and group home) for the elderly in Taiwan. Data were collected from 167 middle-aged and…

Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis

Directory of Open Access Journals (Sweden)

Hedwig S. Kruitwagen

2017-04-01

Full Text Available Summary: Hepatic steatosis is a highly prevalent liver disease, yet research is hampered by the lack of tractable cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of liver organoids for modeling genetic diseases. To examine the possibility of using organoids to model steatosis, we established a long-term feline liver organoid culture with adult liver stem cell characteristics and differentiation potential toward hepatocyte-like cells. Next, organoids from mouse, human, dog, and cat liver were provided with fatty acids. Lipid accumulation was observed in all organoids and interestingly, feline liver organoids accumulated more lipid droplets than human organoids. Finally, we demonstrate effects of interference with β-oxidation on lipid accumulation in feline liver organoids. In conclusion, feline liver organoids can be successfully cultured and display a predisposition for lipid accumulation, making them an interesting model in hepatic steatosis research. : In this study Kruitwagen and colleagues establish and characterize a feline liver organoid culture, which has adult stem cell properties and can be differentiated toward hepatocyte-like cells. They propose liver organoids as a tool to model hepatic steatosis and show that feline liver organoids accumulate more lipids than human organoids when provided with excess fatty acids. Keywords: feline liver organoids, adult liver stem cells, hepatic steatosis, disease modeling, feline hepatic lipidosis, species differences

Behavioural Effects of Adult Vitamin D Deficiency in BALB/c Mice Are not Associated with Proliferation or Survival of Neurons in the Adult Hippocampus.

Directory of Open Access Journals (Sweden)

Natalie J Groves

Full Text Available Epidemiological studies have shown that up to one third of adults have insufficient levels of vitamin D and there is an association between low vitamin D concentrations and adverse brain outcomes, such as depression. Vitamin D has been shown to be involved in processes associated with neurogenesis during development. Therefore, the aim of this study was to test the hypothesis that adult vitamin D (AVD deficiency in BALB/c mice was associated with (a adult hippocampal neurogenesis at baseline, b following 6 weeks of voluntary wheel running and (c a depressive-like phenotype on the forced swim test (FST, which may be linked to alterations in hippocampal neurogenesis. We assessed proliferation and survival of adult born hippocampal neurons by counting the number of cells positive for Ki67 and doublecortin (DCX, and incorporation of 5-Bromo-2'-Deoxyuridine (BrdU within newly born mature neurons using immunohistochemistry. There were no significant effects of diet on number of Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly increased number of Ki67+ cells and BrdU incorporation, and decreased immobility time in the FST, after voluntary wheel running. A significant correlation was found in control mice between immobility time in the FST and level of hippocampal neurogenesis, however, no such correlation was found for AVD-deficient mice. We conclude that AVD deficiency was not associated with impaired proliferation or survival of adult born neurons in BALB/c mice and that the impact on rodent behaviour may not be due to altered neurogenesis per se, but to altered function of new hippocampal neurons or processes independent of adult neurogenesis.

Chinese herbal medicine for Alzheimer's disease: Clinical evidence and possible mechanism of neurogenesis.

Science.gov (United States)

Yang, Wen-Ting; Zheng, Xia-Wei; Chen, Shuang; Shan, Chun-Shuo; Xu, Qing-Qing; Zhu, Jia-Zhen; Bao, Xiao-Yi; Lin, Yan; Zheng, Guo-Qing; Wang, Yan

2017-10-01

Currently, there is lack of cure or disease-modifying treatment for Alzheimer's disease (AD). Chinese herbal medicine (CHM) is purported to ameliorate AD progression, perhaps by promoting hippocampal neurogenesis. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for AD based on high-quality randomized controlled trials (RCTs) and reviewed its possible mechanisms of neurogenesis according to animal-based researches. Twenty eligible studies with 1767 subjects were identified in eight database searches from inception to February 2017. The studies investigated the CHM versus placebo (n=3), CHM versus donepezil (n=9 with 10 comparisons), CHM plus donepezil versus donepezil (n=3), CHM versus a basic treatment (n=3), and CHM plus basic treatment versus basic treatment (n=2). Adverse events were reported in 11 studies, analyzed but not observed in 3 studies, and not analyzed in 6 studies. The main findings of present study are that CHM as adjuvant therapy exerted an additive anti-AD benefit, whereas the efficacy of CHM as a monotherapy was inconclusive. Additionally, CHMs were generally safe and well tolerated in AD patients. Active molecules in frequent constituents of CHMs can alter multiple critical signaling pathways regulating neurogenesis. Thus, the present evidence supports, to a limited extent, the conclusion that CHM can be recommended for routine use in AD patients and its possible mechanism enhances adult hippocampal neurogenesis through activating the multi-signal pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Infectious Diseases in Older Adults of Long-Term Care Facilities: Update on Approach to Diagnosis and Management.

Science.gov (United States)

Jump, Robin L P; Crnich, Christopher J; Mody, Lona; Bradley, Suzanne F; Nicolle, Lindsay E; Yoshikawa, Thomas T

2018-04-01

The diagnosis, treatment, and prevention of infectious diseases in older adults in long-term care facilities (LTCFs), particularly nursing facilities, remains a challenge for all health providers who care for this population. This review provides updated information on the currently most important challenges of infectious diseases in LTCFs. With the increasing prescribing of antibiotics in older adults, particularly in LTCFs, the topic of antibiotic stewardship is presented in this review. Following this discussion, salient points on clinical relevance, clinical presentation, diagnostic approach, therapy, and prevention are discussed for skin and soft tissue infections, infectious diarrhea (Clostridium difficile and norovirus infections), bacterial pneumonia, and urinary tract infection, as well as some of the newer approaches to preventive interventions in the LTCF setting. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Long-Term Care Services for Veterans

Science.gov (United States)

2017-02-14

includes but is not limited to home physical , occupational, or speech therapy ; wound care; and intravenous (IV) care. A VA physician determines that a...restoring/rehabilitating the veteran’s health, such as skilled nursing care, physical therapy , occupational therapy , and IV therapy Same as HBPC... geriatric evaluation,  palliative care,  adult day health care,  homemaker/home health aide care,  respite care, Long-Term Care Services for

Matching Diabetes and Alcoholism: Oxidative Stress, Inflammation, and Neurogenesis Are Commonly Involved

Directory of Open Access Journals (Sweden)

Jorge M. Barcia

2015-01-01

Full Text Available Diabetes and alcohol misuse are two of the major challenges in health systems worldwide. These two diseases finally affect several organs and systems including the central nervous system. Hippocampus is one of the most relevant structures due to neurogenesis and memory-related processing among other functions. The present review focuses on the common profile of diabetes and ethanol exposure in terms of oxidative stress and proinflammatory and prosurvival recruiting transcription factors affecting hippocampal neurogenesis. Some aspects around antioxidant strategies are also included. As a global conclusion, the present review points out some common hits on both diseases giving support to the relations between alcohol intake and diabetes.

Short-term and long-term collaboration benefits on individual recall in younger and older adults

Science.gov (United States)

Stern, Yaakov

2011-01-01

A recent study of younger adults suggests that, compared to repeated individual recall trials, repeated collaborative recall trials produce better individual recall after a short delay (Blumen & Rajaram, 2008). Our study was designed to determine if such collaboration benefits would remain after a one-week delay, in both younger and older adults. Sixty younger (M age = 24.60) and 60 older (M age = 67.35) adults studied a list of words and then completed either two collaborative recall trials followed by two individual recall trials, or four individual recall trials. A five-min delay was inserted between the first three recall trials. The fourth recall trial was administered 1 week later. Collaborative recall was completed in groups of three individuals working together. Both younger and older adults benefitted from repeated collaborative recall trials to a greater extent than repeated individual recall trials, and such collaboration benefits remained after a one-week delay. This is the first demonstration of collaboration benefits on later individual recall at delays as long as 1 week, in both younger and older adults. Findings are discussed within the context of the negative effects of collaboration associated with group memory (collaborative inhibition) and the positive effects of collaboration associated with later individual memory (collaboration benefits). PMID:21264617

Cardiovascular responses to orthostasis: methods, assessments, and their association with falls in older adults in long-term care

OpenAIRE

Shaw, Brett Harrison

2013-01-01

Background: Orthostatic hypotension (OH) refers to a significant decline in blood pressure that occurs upon assuming an upright posture and represents an intrinsic risk factor for falls in older adults. Methods: Beat-to-beat blood pressure and cerebral blood flow velocity responses were assessed during a passive seated orthostatic stress test (PSOST). In healthy controls, PSOST responses were compared to head up tilt (the ‘gold-standard’). In a cohort of long-term care residents, data from PS...

Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature Aging

Directory of Open Access Journals (Sweden)

Alexander J. Stankiewicz

2017-10-01

Full Text Available Chronic high caloric intake (HCI is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior. A remarkable decline in adult neurogenesis in 1-year old HCI animals, amounting to only 21% of that in age-matched Control, exceeds age-dependent decline observed in normal 3-year old zebrafish. This is associated with misalignment or reduced amplitude of daily patterns for principal cell cycle regulators, cyclins A and B, and p20, in brain tissue. Together, these data establish HCI in zebrafish as a model for metabolically induced premature aging of sleep, circadian functions, and adult neurogenesis, allowing for a high throughput approach to mechanistic studies and drug trials in a diurnal vertebrate.

Treatment outcome and long-term stability of skeletal changes following maxillary distraction in adult subjects of cleft lip and palate

Directory of Open Access Journals (Sweden)

Satinder Pal Singh

2012-01-01

Full Text Available Aim : To evaluate the treatment outcome and long-term stability of skeletal changes following maxillary advancement with distraction osteogenesis in adult subjects of cleft lip and palate. Materials and Methods: Total 12 North Indian adult patients in the age range of 17-34 years with cleft lip and palate underwent advancement of maxilla by distraction osteogenesis. Lateral cephalograms recorded prior to distraction, at the end of distraction, 6 months after distraction, and at least 24 months (mean 25.5 ± 1.94 months after distraction osteogenesis were used for the evaluation of treatment outcome and long-term stability of the skeletal changes. Descriptive analysis, ANOVA, and post-hoc test were used, and P-value 0.05 was considered as a statistically significant level. Results: Maxillary distraction resulted in significant advancement of maxilla (P<0.001. Counterclockwise rotation of the palatal plane took place after maxillary distraction. The position of the mandible and facial heights were stable during distraction. During the first 6 months of the post-distraction period, the maxilla showed relapse of approximately 30%. However, after 6 months post distraction, the relapse was very negligible. Conclusions: Successful advancement of maxilla was achieved by distraction osteogenesis in adult subjects with cleft lip and palate. Most of the relapse occurred during the first 6 months of post-distraction period, and after that the outcomes were stable.

Conditional reduction of adult born doublecortin-positive neurons reversibly impairs selective behaviours

Directory of Open Access Journals (Sweden)

Lillian eGarrett

2015-11-01

Full Text Available Adult neurogenesis occurs in the adult mammalian subventricular zone (SVZ along the walls of the lateral ventricles and the subgranular zone (SGZ of the hippocampal dentate gyrus. While a burgeoning body of research implicates adult neurogenesis in olfactory bulb (OB - and hippocampal-related behaviors, the precise function continues to elude. To further assess the behavioral importance of adult neurogenesis, we herein generated a novel inducible transgenic mouse model of adult neurogenesis reduction where mice with CreERT2 under doublecortin (DCX promoter control were crossed with mice where diphtheria toxin A (DTA was driven by the Rosa26 promoter. Activation of DTA, through the administration of tamoxifen (TAM, results in a specific reduction of DCX+ immature neurons in both the hippocampal dentate gyrus and OB. We show that the decrease of DCX+ cells causes impaired social discrimination ability in both young adult (from 3 months and middle (from 10 months aged mice. Furthermore, these animals showed an age-independent altered coping behavior in the Forced Swim Test without clear changes in anxiety-related behavior. Notably, these behavior changes were reversible on repopulating the neurogenic zones with DCX+ cells on cessation of the tamoxifen treatment, demonstrating the specificity of this effect. Overall, these results support the notion that adult neurogenesis plays a role in social memory and in stress coping but not necessarily in anxiety-related behavior.

Long-term results of splenectomy in adult chronic immune thrombocytopenia.

Science.gov (United States)

Guan, Yue; Wang, Shixuan; Xue, Feng; Liu, Xiaofan; Zhang, Lei; Li, Huiyuan; Yang, Renchi

2017-03-01

We performed this study in adult patients with chronic primary immune thrombocytopenia to explore the long-term efficacy and safety of splenectomy. Data of 174 patients who underwent splenectomy in our hospital from 1994 to 2014 were analyzed. After splenectomy, 126 (72.4%) patients achieved a complete response (CR) and 28 (16.1%) achieved a response (R). Thirty-two (20.8%) responders relapsed with a median time of 24 months. Compared with non-responders and recurrent patients, the stable responders were younger and had higher preoperation and postoperation peak platelet count, later peak platelet count emergence time, and more megakaryocytes. Corticosteroid-dependent patients were more likely to response to splenectomy than those refractory to corticosteroid. We performed a relapse-free survival analysis among the 154 responders. In univariate analyses, corticosteroid dependent and time from diagnosis to splenectomy ≤24 months showed predictive value to persistent response. But only corticosteroid dependent was a significant predictor in multivariate analysis. The 30-d complication rate after the surgery was 25.9%. There were five (2.9%) patients experienced thrombosis and three (1.7%) refractory patients died during follow-up. Splenectomy was a safe treatment with a cure rate of 58.0%. Corticosteroid dependent showed predictive value to persistent response. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ramipril mitigates radiation-induced impairment of neurogenesis in the rat dentate gyrus

Directory of Open Access Journals (Sweden)

Lapanowski Karen

2010-02-01

Full Text Available Abstract Background Sublethal doses of whole brain irradiation (WBI are commonly administered therapeutically and frequently result in late delayed radiation injuries, manifesting as severe and irreversible cognitive impairment. Neural progenitors within the subgranular zone (SGZ of the dentate gyrus are among the most radiosensitive cell types in the adult brain and are known to participate in hippocampal plasticity and normal cognitive function. These progenitors and the specialized SZG microenvironment required for neuronal differentiation are the source of neurogenic potential in the adult dentate gyrus, and provide a continuous supply of immature neurons which may then migrate into the adjacent granule cell layer to become mature granule cell neurons. The extreme radiosensitivity of these progenitors and the SGZ microenvironment suggests the hippocampus as a prime target for radiation-induced cognitive impairment. The brain renin-angiotensin system (RAS has previously been implicated as a potent modulator of neurogenesis within the SGZ and selective RAS inhibitors have been implicated as mitigators of radiation brain injury. Here we investigate the angiotensin converting enzyme (ACE inhibitor, ramipril, as a mitigator of radiation injury in this context. Methods Adult male Fisher 344 rats received WBI at doses of 10 Gy and 15 Gy. Ramipril was administered beginning 24 hours post-WBI and maintained continuously for 12 weeks. Results Ramipril produced small but significant reductions in the deleterious effects of radiation on progenitor proliferation and neuronal differentiation in the rat dentate gyrus following 10 Gy-WBI, but was not effective following 15 Gy-WBI. Ramipril also reduced the basal rate of neurogenesis within the SGZ in unirradiated control rats. Conclusions Our results indicate that chronic ACE inhibition with ramipril, initiated 24 hours post-irradiation, may reduce apoptosis among SGZ progenitors and/or inflammatory

Long-Term Implications of Welfare Reform for the Development of Adolescents and Young Adults

Science.gov (United States)

Chase-Lansdale, P. Lindsay; Cherlin, Andrew J.; Guttmannova, Katarina; Fomby, Paula; Ribar, David C.; Coley, Rebekah Levine

2011-01-01

We draw upon the 3-wave longitudinal dataset called Welfare Children and Families: A Three-City Study to examine the long-term implications for adolescents and young adults (N=783) of mothers’ welfare receipt and labor force participation from 1999 to 2005. In general, changes in mothers’ work and welfare patterns were not associated with deterioration or improvement in youth development (ages 16 to 20 years at wave 3). The few significant associations suggested that youth whose mothers increased employment (net of welfare participation) were more likely to show declines in serious behavior problems and delinquency compared to youth whose mothers were unemployed or employed part-time during the study period. Welfare roll exits (controlling for employment experiences) were unrelated to adolescent and young adult outcomes. Mothers’ employment transitions were linked to improvements in household income and mothers’ self esteem in addition to reductions in financial strain and their own illegal activities. However, these associations did not explain the relation between maternal employment and youths’ improved behavior. These results do not support the predictions of either the supporters or the opponents of welfare reform, an outcome we discuss. PMID:21966077

Long-term control medication use and asthma control status among children and adults with asthma.

Science.gov (United States)

Zahran, Hatice S; Bailey, Cathy M; Qin, Xiaoting; Johnson, Carol

2017-12-01

Uncontrolled asthma decreases quality of life and increases health care use. Most people with asthma need daily use of long-term control (LTC) medications for asthma symptoms and to prevent asthma attacks. Ongoing assessment of a person's level of asthma control and medication use is important in determining the effectiveness of current treatment to decrease the frequency and intensity of symptoms and functional limitations. To assess the use of LTC medication among children and adults with current asthma and identify contributing factors for LTC medication use. We used the 2006-2010 Behavioral Risk Factor Surveillance System (BRFSS) child and adult Asthma Call-back Survey (ACBS) data to assess the level of asthma control and LTC medication use. Asthma control was classified as well controlled and uncontrolled using guideline-based measures. We used multivariable logistic regression models to identify contributing factors for LTC medication use and having uncontrolled asthma. Among persons with current asthma, 46.0% of children and 41.5% of adults were taking LTC medications and 38.4% of children and 50.0% of adults had uncontrolled asthma. Among children who had uncontrolled asthma (38.4%), 24.1% were taking LTC medications and 14.3% were not taking LTC medications. Among adults who had uncontrolled asthma (50.0%), 26.7% were taking LTC medications and 23.3% were not taking LTC medications. Using BRFSS ACBS data to assess the level of asthma control and LTC medication use can identify subpopulations of persons with asthma who receive suboptimal treatment, for which better asthma-related medical treatment and management are needed.

Aminopropyl carbazole analogues as potent enhancers of neurogenesis.

Science.gov (United States)

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

2013-11-15

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