scholarly journals Adult neurogenesis in natural populations

2001 ◽  
Vol 79 (4) ◽  
pp. 297-302 ◽  
Author(s):  
R Boonstra ◽  
L Galea ◽  
S Matthews ◽  
J M Wojtowicz
Keyword(s):  
Adult Neurogenesis ◽  
Mammalian Species ◽  
Natural Populations ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Biologically Relevant ◽  
Evolutionarily Conserved ◽  
Functional Consequences ◽  
Song Production ◽  
And Function

The dogma that the adult brain produces no new neurons has been overturned, but the critics are still asking, so what? Is adult neurogenesis a biologically relevant phenomenon, or is it perhaps harmful because it disrupts the existing neuronal circuitry? Considering that the phenomenon is evolutionarily conserved in all mammalian species examined to date and that its relevance has been well documented in non-mammalian species, it seems self-evident that neurogenesis in adult mammals must have a role. In birds, it has been established that neurogenesis varies dramatically with seasonal changes in song production. In chickadees, the learning behaviour related to finding stored food is also correlated with seasonal adult neurogenesis. Such studies are still nonexistent in mammals, but the related evidence suggests that neurogenesis does vary seasonally in hamsters and shows sexual differences in meadow voles. To promote studies on natural populations asking fundamental questions of the purpose and function of neurogenesis, we organized a Workshop on "Hippocampal Neurogenesis in Natural Populations" in Toronto in May 2000. The Workshop highlighted recent discoveries in neurogenesis from the lab, and focused on its functional consequences. The consensus at the Workshop was that demonstration of a role for neurogenesis in natural behaviours will ultimately be essential if we are to understand the purpose and function of neurogenesis in humans.Key words: neurogenesis, hippocampus, dentate gyrus, learning, memory, wild population.

scholarly journals Genome-enabled discovery of evolutionary divergence in brains and behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chinar Patil ◽  
Jonathan B. Sylvester ◽  
Kawther Abdilleh ◽  
Michael W. Norsworthy ◽  
Karen Pottin ◽  
...  
Keyword(s):  
Reverse Genetics ◽  
Natural Populations ◽  
Bmp Signaling ◽  
Evolutionary Divergence ◽  
Genetic Changes ◽  
Form And Function ◽  
Brain Gene Expression ◽  
Evolutionarily Conserved ◽  
And Function ◽  
And Behavior

AbstractLake Malawi cichlid fishes exhibit extensive divergence in form and function built from a relatively small number of genetic changes. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. Genome regions near differentiated variants are enriched for craniofacial, neural and behavioral categories. Following leads from genome sequence, we used rock- vs. sand-species and their hybrids to (i) delineate the push–pull roles of BMP signaling and irx1b in the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results demonstrate how divergent genome sequences can predict differences in key evolutionary traits. We highlight the promise of evolutionary reverse genetics—the inference of phenotypic divergence from unbiased genome sequencing and then empirical validation in natural populations.

scholarly journals A Common Language: How Neuroimmunological Cross Talk Regulates Adult Hippocampal Neurogenesis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Odette Leiter ◽  
Gerd Kempermann ◽  
Tara L. Walker
Keyword(s):  
Immune System ◽  
Adult Neurogenesis ◽  
Immune Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Normal Brain ◽  
Intrinsic Cues ◽  
Normal Brain Function ◽  
The Brain

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

scholarly journals Androgens Increase Survival of Adult-Born Neurons in the Dentate Gyrus by an Androgen Receptor-Dependent Mechanism in Male Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (9) ◽  
pp. 3294-3304 ◽  
Author(s):  
D. K. Hamson ◽  
S. R. Wainwright ◽  
J. R. Taylor ◽  
B. A. Jones ◽  
N. V. Watson ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Male Rats ◽  
Male Rat ◽  
Testicular Feminization ◽  
Wild Type ◽  
Adult Born Neurons

Gonadal steroids are potent regulators of adult neurogenesis. We previously reported that androgens, such as testosterone (T) and dihydrotestosterone (DHT), but not estradiol, increased the survival of new neurons in the dentate gyrus of the male rat. These results suggest androgens regulate hippocampal neurogenesis via the androgen receptor (AR). To test this supposition, we examined the role of ARs in hippocampal neurogenesis using 2 different approaches. In experiment 1, we examined neurogenesis in male rats insensitive to androgens due to a naturally occurring mutation in the gene encoding the AR (termed testicular feminization mutation) compared with wild-type males. In experiment 2, we injected the AR antagonist, flutamide, into castrated male rats and compared neurogenesis levels in the dentate gyrus of DHT and oil-treated controls. In experiment 1, chronic T increased hippocampal neurogenesis in wild-type males but not in androgen-insensitive testicular feminization mutation males. In experiment 2, DHT increased hippocampal neurogenesis via cell survival, an effect that was blocked by concurrent treatment with flutamide. DHT, however, did not affect cell proliferation. Interestingly, cells expressing doublecortin, a marker of immature neurons, did not colabel with ARs in the dentate gyrus, but ARs were robustly expressed in other regions of the hippocampus. Together these studies provide complementary evidence that androgens regulate adult neurogenesis in the hippocampus via the AR but at a site other than the dentate gyrus. Understanding where in the brain androgens act to increase the survival of new neurons in the adult brain may have implications for neurodegenerative disorders.

scholarly journals Notch signalling in T cell homeostasis and differentiation

Open Biology ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 190187 ◽  
Author(s):  
Joshua D. Brandstadter ◽  
Ivan Maillard
Keyword(s):  
T Cell ◽  
Relevant Information ◽  
Notch Signalling ◽  
T Cell Homeostasis ◽  
Notch Signalling Pathway ◽  
Cell Responses ◽  
Open Questions ◽  
Evolutionarily Conserved ◽  
Functional Consequences ◽  
And Function

The evolutionarily conserved Notch signalling pathway regulates the differentiation and function of mature T lymphocytes with major context-dependent consequences in host defence, autoimmunity and alloimmunity. The emerging effects of Notch signalling in T cell responses build upon a more established role for Notch in T cell development. Here, we provide a critical review of this burgeoning literature to make sense of what has been learned so far and highlight the experimental strategies that have been most useful in gleaning physiologically relevant information. We outline the functional consequences of Notch signalling in mature T cells in addition to key specific Notch ligand–receptor interactions and downstream molecular signalling pathways. Our goal is to help clarify future directions for this expanding body of work and the best approaches to answer important open questions.

scholarly journals Genome-enabled discovery of evolutionary divergence in brains and behavior 

2021 ◽  
Author(s):  
Chinar Patil ◽  
Jonathan Sylvester ◽  
Kawther Abdilleh ◽  
Michael W. Norsworthy ◽  
Karen Pottin ◽  
...  
Keyword(s):  
Reverse Genetics ◽  
Natural Populations ◽  
Bmp Signaling ◽  
Evolutionary Divergence ◽  
Genetic Changes ◽  
Form And Function ◽  
Brain Gene Expression ◽  
Evolutionarily Conserved ◽  
And Function ◽  
And Behavior

Abstract Lake Malawi cichlid fishes exhibit extensive divergence in form and function built from a relatively small number of genetic changes. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. Genome regions near differentiated variants are enriched for craniofacial, neural and behavioral categories. Following leads from genome sequence, we used rock- vs. sand- species and their hybrids to (i) delineate the push-pull roles of BMP signaling and irx1b in the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results demonstrate how divergent genome sequences can predict differences in key evolutionary traits. We highlight the promise of evolutionary reverse genetics – the inference of divergence in phenotype from genome sequencing in natural populations.

scholarly journals New neurons in old brains: A cautionary tale for the analysis of neurogenesis in post-mortem tissue.

2021 ◽  
Author(s):  
Dylan J Terstege ◽  
Kwaku Addo-Osafo ◽  
Gordon Campbell Teskey ◽  
Jonathan R Epp
Keyword(s):  
Adult Neurogenesis ◽  
Mammalian Species ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Tissue Fixation ◽  
Post Mortem ◽  
Biological Difference ◽  
High Profile ◽  
Age Related ◽  
Morphological Detail

Adult neurogenesis has primarily been examined in two key regions in the mammalian brain, the subgranular zone of the hippocampus and the subventricular zone. The proliferation and integration of newly generated neurons has been observed widely in adult mammalian species including the human hippocampus. Recent high-profile studies have suggested however, that this process is considerably reduced in humans, occurring in children but declining rapidly and nearly completely in the adult brain. In comparison, rodent studies also show age-related decline but a greater degree of proliferation of new neurons in adult animals. Here, we examine whether differences in tissue fixation, rather than biological difference in human versus rodent studies might account for the diminished levels of neurogenesis sometimes observed in the human brain. To do so we analyzed neurogenesis in the hippocampus of rats that were either perfusion-fixed or the brains extracted and immersion-fixed at various post-mortem intervals. We observed an interaction between animal age and the time delay between death and tissue fixation. While similar levels of neurogenesis were observed in young rats regardless of fixation, older rats had significantly fewer labeled neurons when fixation was not immediate. Furthermore, the morphological detail of the labeled neurons was significantly reduced in the delayed fixation conditions at all ages. This study highlights critical concerns that must be considered when using post-mortem tissue to quantify adult neurogenesis.

scholarly journals Pro-NGF Disrupts Adult Neurogenesis in Humans and Mice Affected by Alzheimer's Disease

2021 ◽  
Author(s):  
Bolanle Olabiyi ◽  
Catherine Fleitas ◽  
Bahira Zammou ◽  
Isidro Ferrer ◽  
Claire Rampon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Neutralizing Antibodies ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Neurotrophin Receptor ◽  
Morris Water Maze Test ◽  
Healthy Humans

Abstract In recent decades, neurogenesis in adult brain has been well demonstrated in a number of animal species, including humans. Interestingly, work with rodents has shown that adult neurogenesis in the dentate gyrus (DG) of the hippocampus is vital for some cognitive aspects, as increasing neurogenesis improves memory while its disruption triggers the opposite effect. Adult neurogenesis declines with age and has been suggested to play a role in impaired progressive learning and memory loss seen in Alzheimer’s disease (AD). Therefore, therapeutic strategies designed to boost adult hippocampal neurogenesis may be beneficial for the treatment of AD. The precursor forms of neurotrophins, such as pro-NGF, display remarkable increase during AD in the hippocampus and entorhinal cortex. In contrast to mature NGF, pro-NGF exerts adverse functions in survival, proliferation and differentiation. Hence, we hypothesized that pro-NGF and its receptor p75NTR contribute to disrupting adult hippocampal neurogenesis during AD. In this study, we took advantage of the availability of mouse models of AD (APP/PS1) and AD human samples to address the role of pro-NGF/p75NTR signalling in different aspects of adult neurogenesis. Neuroprogenitors of adult mice and human DG samples were identified by immunofluorescence with doublecortin (DCX) antibodies. Interestingly, DCX + progenitors in healthy humans and control animals express p75 neurotrophin receptor (p75NTR). However, this expression is notably decreased in AD conditions. In APP/PS1 mice, memory and cognition were severely impaired. In order to assess the contribution of the pro-NGF/p75NTR pathway to these memory deficits, we injected pro-NGF neutralizing antibodies (ANTI-PRONGF) into the DG of control and APP/PS1 mice which memory was evaluated in Morris water maze test. We observed that anti-pro-NGF injection significantly improved the performance of APP/PS1 animals, but not controls. Interestingly, improved memory in APP/PS1 animals after injection of ANTI-PRONGF correlated with an increase in DCX + progenitors in the DG region of these animals. In summary, our results suggest that pro-NGF is involved in disrupting spatial memory in AD, at least in part by blocking adult neurogenesis. Moreover, we propose that adult neurogenesis alteration could serve as alternative approach towards understanding AD pathology, and additionally offer pro-NGF/p75NTR signalling as a promising therapeutic target.

A Hypothesis About the Role of Adult Neurogenesis in Hippocampal Function

Physiology ◽  
2004 ◽  
Vol 19 (5) ◽  
pp. 253-261 ◽  
Author(s):  
Alejandro F. Schinder ◽  
Fred H. Gage
Keyword(s):  
Adult Neurogenesis ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Hippocampal Function ◽  
Hippocampal Plasticity ◽  
Functional Relevance ◽  
And Function ◽  
Precise Role

The functional relevance of adult hippocampal neurogenesis has long been a matter of intense experimentation and debate, but the precise role of new neurons has not been sufficiently elaborated. Here we propose a hypothesis in which specific features of newly generated neurons contribute to hippocampal plasticity and function and discuss the most recent and relevant findings in the context of the proposed hypothesis.

scholarly journals proNGF Involvement in the Adult Neurogenesis Dysfunction in Alzheimer’s Disease

2021 ◽  
Vol 22 (19) ◽  
pp. 10744
Author(s):  
Bolanle Fatimat Olabiyi ◽  
Catherine Fleitas ◽  
Bahira Zammou ◽  
Isidro Ferrer ◽  
Claire Rampon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Neutralizing Antibodies ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Neurotrophin Receptor ◽  
Morris Water Maze Test ◽  
Healthy Humans

In recent decades, neurogenesis in the adult brain has been well demonstrated in a number of animal species, including humans. Interestingly, work with rodents has shown that adult neurogenesis in the dentate gyrus (DG) of the hippocampus is vital for some cognitive aspects, as increasing neurogenesis improves memory, while its disruption triggers the opposite effect. Adult neurogenesis declines with age and has been suggested to play a role in impaired progressive learning and memory loss seen in Alzheimer’s disease (AD). Therefore, therapeutic strategies designed to boost adult hippocampal neurogenesis may be beneficial for the treatment of AD. The precursor forms of neurotrophins, such as pro-NGF, display remarkable increase during AD in the hippocampus and entorhinal cortex. In contrast to mature NGF, pro-NGF exerts adverse functions in survival, proliferation, and differentiation. Hence, we hypothesized that pro-NGF and its p75 neurotrophin receptor (p75NTR) contribute to disrupting adult hippocampal neurogenesis during AD. To test this hypothesis, in this study, we took advantage of the availability of mouse models of AD (APP/PS1), which display memory impairment, and AD human samples to address the role of pro-NGF/p75NTR signaling in different aspects of adult neurogenesis. First, we observed that DG doublecortin (DCX) + progenitors express p75NTR both, in healthy humans and control animals, although the percentage of DCX+ cells are significantly reduced in AD. Interestingly, the expression of p75NTR in these progenitors is significantly decreased in AD conditions compared to controls. In order to assess the contribution of the pro-NGF/p75NTR pathway to the memory deficits of APP/PS1 mice, we injected pro-NGF neutralizing antibodies (anti-proNGF) into the DG of control and APP/PS1 mice and animals are subjected to a Morris water maze test. Intriguingly, we observed that anti-pro-NGF significantly restored memory performance of APP/PS1 animals and significantly increase the percentage of DCX+ progenitors in the DG region of these animals. In summary, our results suggest that pro-NGF is involved in disrupting spatial memory in AD, at least in part by blocking adult neurogenesis. Moreover, we propose that adult neurogenesis alteration should be taken into consideration for better understanding of AD pathology. Additionally, we provide a new molecular entry point (pro-NGF/p75NTR signaling) as a promising therapeutic target in AD.

scholarly journals Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

2021 ◽  
Vol 22 (7) ◽  
pp. 3342
Author(s):  
Hansruedi Büeler
Keyword(s):  
Stem Cell ◽  
Mood Disorders ◽  
Adult Neurogenesis ◽  
Cell Function ◽  
Natural Aging ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Induced Mood ◽  
Newborn Neurons

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.

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