Abstract WMP42: Remote Ischemic Stroke Decreases Quiescence and Increases Neurogenic Activation of Radial Glia-like Precursors in the Subgranular Zone of the Dentate Gyrus in Adult Mice

Adult neurogenesis occurs in two discrete neurogenic niches in the mammalian brain: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampal formation. Under physiologic conditions, neurogenesis in these regions is thought to be important for the maintenance and reorganization of interneurons in the olfactory bulb (SVZ), and the modulation and refinement of existing circuits in the dentate gyrus (SGZ). In rodents, stroke enhances neurogenesis in these regions, and stroke-induced neurogenesis appears to play a role in functional recovery. However, little is known about the behavior of quiescent vs. activated pools of neural stem cells in response to stroke, or the mechanisms of stroke-induced neurogenesis at the cellular level. Here we tested the hypothesis that stroke-induced neurogenesis involves the activation of quiescent stem cell pools, either alone or in combination with further differentiation of activated precursors. We used a genetic labeling strategy for in vivo lineage tracing of quiescent, nestin-expressing radial glia-like (RGL) precursors in the SGZ to elucidate the effect of remote focal ischemic infarction on RGLs at a clonal level. Unilateral infarction of the visual cortex by photothrombosis in transgenic mice caused an increase in the number of differentiated neuronal precursors and a decrease in the number of quiescent RGLs in the ipsilateral SGZ. Furthermore, among activated RGL clones, there was an increase in symmetric and neurogenic RGL divisions in response to stroke, with a concomitant loss of astrogliogenic RGL divisions. These preliminary results suggest that stroke may alter hippocampal neurogenesis from a distance by activating quiescent RGL pools in the SGZ through an as-of-yet unidentified mechanism and pushing them toward a neuronal fate. In turn, this may accelerate the time-dependent depletion of this RGL population. We speculate that this phenomenon contributes to cognitive changes associated with stroke and may represent a target for pharmacological intervention.

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Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1508545112 ◽

2015 ◽

Vol 112 (30) ◽

pp. 9484-9489 ◽

Cited By ~ 59

Author(s):

Gerald J. Sun ◽

Yi Zhou ◽

Ryan P. Stadel ◽

Jonathan Moss ◽

Jing Hui A. Yong ◽

...

Keyword(s):

Dentate Gyrus ◽

Radial Glia ◽

Lineage Tracing ◽

Mammalian Brain ◽

Gabaergic Interneuron ◽

Granule Neurons ◽

Glutamatergic Neurons ◽

Tangential Migration ◽

Neuronal Precursors ◽

Adult Mammalian Brain

In a classic model of mammalian brain formation, precursors of principal glutamatergic neurons migrate radially along radial glia fibers whereas GABAergic interneuron precursors migrate tangentially. These migration modes have significant implications for brain function. Here we used clonal lineage tracing of active radial glia-like neural stem cells in the adult mouse dentate gyrus and made the surprising discovery that proliferating neuronal precursors of glutamatergic granule neurons exhibit significant tangential migration along blood vessels, followed by limited radial migration. Genetic birthdating and morphological and molecular analyses pinpointed the neuroblast stage as the main developmental window when tangential migration occurs. We also developed a partial “whole-mount” dentate gyrus preparation and observed a dense plexus of capillaries, with which only neuroblasts, among the entire population of progenitors, are directly associated. Together, these results provide insight into neuronal migration in the adult mammalian nervous system.

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Postnatal Development of the Hippocampus in Male Albino Rats: A Histomorphometric Study

QJM ◽

10.1093/qjmed/hcaa040 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

A A A Baraka ◽

K A Hafez ◽

A I A Othman ◽

A M M Sadek

Keyword(s):

Dentate Gyrus ◽

Postnatal Development ◽

Learning And Memory ◽

Hippocampal Formation ◽

Critical Role ◽

Mammalian Brain ◽

Albino Rats ◽

Ammon's Horn ◽

Hippocampus Proper ◽

Ammon’S Horn

Abstract Introduction In recent year deterioration in cognitive, learning, and memory become one of the significant problems in human life. Hippocampus is a pivotal part of the brain’s limbic system which serves a critical role in memory, learning process and regulating the emotions. In most regions of the brain, neurons are generated only at specific periods of early development, and not born in the adulthood. In contrast, hippocampal neurons are generated throughout development and adult life. The hippocampal dentate gyrus was reported to be one of the few regions of the mammalian brain where neurogenesis continue to occur throughout adulthood. The neurogenesis in the dentate gyrus was thought to play an important role in hippocampus-dependent learning and memory. The hippocampal formation is composed of the hippocampus proper, the dentate gyrus and the subiculum. The hippocampus proper is the largest part and is subdivided into fields designated as Cornu Ammonis or Ammon’s horn (CA) from CA1 to CA4. Ammon's horn is continuous with the subiculum, which acts as the main output source of the hippocampal formation. Aim of the Study To study the postnatal development of the hippocampal formation. Materials and Methods Five male albino rats from the following postnatal ages day 1, week 1, week 2, week3 and week 4 were studied by histological, immunohistochemical, and morphometric methods. Results The general architecture of the hippocampus proper with its polymorphic, pyramidal, and molecular layers was present at day1, whereas the details of the adult structure appeared at week 2. In the dentate gyrus, distinct lamination appeared at week 1 and its maturation continued with the production of neurons at the interhilar zone that peaked at week 2. The number and density of pyramidal axons and dendrites increase by age. Astrocytes increased in size and staining affinity for glial filaments, and acquired a stellate shape with age. Furthermore, the number of granule cell layers increased concomitantly with the increase in thickness of the molecular and polymorphic layers of both the hippocampus proper and the dentate gyrus. Conclusion The important sequences of events in the growth and maturation of the hippocampal formation in male albino rat occurred in the first 2 postnatal weeks.

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Red Ginseng Attenuates Aβ-Induced Mitochondrial Dysfunction and Aβ-mediated Pathology in an Animal Model of Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20123030 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3030 ◽

Cited By ~ 10

Author(s):

Soo Jung Shin ◽

Seong Gak Jeon ◽

Jin-il Kim ◽

Yu-on Jeong ◽

Sujin Kim ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hippocampal Formation ◽

Experimental Models ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Red Ginseng ◽

Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aβ) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator or trigger for AD development. Interestingly, red ginseng (RG) has been demonstrated to have beneficial effects on AD pathology. However, there is no evidence showing whether RG extract (RGE) can inhibit the mitochondrial deficit-mediated pathology in the experimental models of AD. The effects of RGE on Aβ-mediated mitochondrial deficiency were investigated in both HT22 mouse hippocampal neuronal cells and the brains of 5XFAD Aβ-overexpressing transgenic mice. To examine whether RGE can affect mitochondria-related pathology, we used immunohistostaining to study the effects of RGE on Aβ accumulation, neuroinflammation, neurodegeneration, and impaired adult hippocampal neurogenesis in hippocampal formation of 5XFAD mice. In vitro and in vivo findings indicated that RGE significantly improves Aβ-induced mitochondrial pathology. In addition, RGE significantly ameliorated AD-related pathology, such as Aβ deposition, gliosis, and neuronal loss, and deficits in adult hippocampal neurogenesis in brains with AD. Our results suggest that RGE may be a mitochondria-targeting agent for the treatment of AD.

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Radial glial cells in the adult dentate gyrus: what are they and where do they come from?

F1000Research ◽

10.12688/f1000research.12684.1 ◽

2018 ◽

Vol 7 ◽

pp. 277 ◽

Cited By ~ 32

Author(s):

Daniel A. Berg ◽

Allison M. Bond ◽

Guo-li Ming ◽

Hongjun Song

Keyword(s):

Stem Cells ◽

Dentate Gyrus ◽

Radial Glia ◽

Neural Precursor Cells ◽

Neural Precursor ◽

Subgranular Zone ◽

Adult Neural Stem Cell ◽

Radial Glial Cells ◽

Embryonic Origin ◽

Radial Glial

Adult neurogenesis occurs in the dentate gyrus in the mammalian hippocampus. These new neurons arise from neural precursor cells named radial glia-like cells, which are situated in the subgranular zone of the dentate gyrus. Here, we review the emerging topic of precursor heterogeneity in the adult subgranular zone. We also discuss how this heterogeneity may be established during development and focus on the embryonic origin of the dentate gyrus and radial glia-like stem cells. Finally, we discuss recently developed single-cell techniques, which we believe will be critical to comprehensively investigate adult neural stem cell origin and heterogeneity.

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Lineage tracing reveals the hierarchical relationship between neural stem cell populations in the mouse forebrain

Scientific Reports ◽

10.1038/s41598-019-54143-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Nadia Sachewsky ◽

Wenjun Xu ◽

Tobias Fuehrmann ◽

Derek van der Kooy ◽

Cindi M. Morshead

Keyword(s):

Neural Development ◽

Lineage Tracing ◽

Mammalian Brain ◽

Cell Populations ◽

Neural Repair ◽

Hierarchical Relationship ◽

Asymmetric Divisions ◽

Stem Cell Populations ◽

Adult Mammalian Brain

AbstractSince the original isolation of neural stem cells (NSCs) in the adult mammalian brain, further work has revealed a heterogeneity in the NSC pool. Our previous work characterized a distinct, Oct4 expressing, NSC population in the periventricular region, through development and into adulthood. We hypothesized that this population is upstream in lineage to the more abundant, well documented, GFAP expressing NSC. Herein, we show that Oct4 expressing NSCs give rise to neurons, astrocytes and oligodendrocytes throughout the developing brain. Further, transgenic inducible mouse models demonstrate that the rare Oct4 expressing NSCs undergo asymmetric divisions to give rise to GFAP expressing NSCs in naïve and injured brains. This lineage relationship between distinct NSC pools contributes significantly to an understanding of neural development, the NSC lineage in vivo and has implications for neural repair.

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Adult hippocampal neurogenesis of mammals: evolution and life history

Biology Letters ◽

10.1098/rsbl.2008.0511 ◽

2008 ◽

Vol 5 (1) ◽

pp. 141-144 ◽

Cited By ~ 50

Author(s):

Irmgard Amrein ◽

Hans-Peter Lipp

Keyword(s):

Hippocampal Formation ◽

Mammalian Species ◽

Critical Role ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Mammalian Brain ◽

Spatial Learning And Memory ◽

Species Specific ◽

Species Being

Substantial production of new neurons in the adult mammalian brain is restricted to the olfactory system and the hippocampal formation. Its physiological and behavioural role is still debated. By comparing adult hippocampal neurogenesis (AHN) across many mammalian species, one might recognize a common function. AHN is most prominent in rodents, but shows considerable variability across species, being lowest or missing in primates and bats. The latter finding argues against a critical role of AHN in spatial learning and memory. The common functional denominator across all species investigated thus far is a strong decline of AHN from infancy to midlife. As predicted by Altman and colleagues in 1973, this implies a role in transforming juvenile unpredictable to predictable behaviour, typically characterizing mammalian behaviour once reproductive competence has been attained. However, as only a fraction of mammalian species has been investigated, further comparative studies are necessary in order to recognize whether AHN has a common unique function, or whether it mediates species-specific hippocampal functions.

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Plantar Stimulations during 3-Day Hindlimb Unloading Prevent Loss of Neural Progenitors and Maintain ERK1/2 Activity in the Rat Hippocampus

Life ◽

10.3390/life11050449 ◽

2021 ◽

Vol 11 (5) ◽

pp. 449

Author(s):

Anna S. Berezovskaya ◽

Sergey A. Tyganov ◽

Svetlana D. Nikolaeva ◽

Alexandra A. Naumova ◽

Boris S. Shenkman ◽

...

Keyword(s):

Dentate Gyrus ◽

Cognitive Functions ◽

Simulated Microgravity ◽

Hippocampal Neurogenesis ◽

Neural Progenitors ◽

Hindlimb Unloading ◽

Subgranular Zone ◽

Physically Active ◽

Active Life ◽

Reduced Physical Activity

Adult neurogenesis is a flexible process that depends on the environment and correlates with cognitive functions. Cognitive functions are impaired by various factors including space flight conditions and reduced physical activity. Physically active life significantly improves both cognition and the hippocampal neurogenesis. Here, we analyzed how 3-day simulated microgravity caused by hindlimb unloading (HU) or dynamic foot stimulation (DFS) during HU can affect the hippocampal neurogenesis. Adult Wistar rats were recruited in the experiments. The results demonstrated a decrease in the number of doublecortine (DCX) positive neural progenitors, but proliferation in the subgranular zone of the dentate gyrus was not changed after 3-day HU. Analysis of the effects of DFS showed restoration of neural progenitor population in the subgranular zone of the dentate gyrus. Additionally, we analyzed activity of the cRaf/ERK1/2 pathway, which is one of the major players in the regulation of neuronal differentiation. The results demonstrated inhibition of cRaf/ERK1/2 signaling in the hippocampus of HU rats. In DFS rats, no changes in the activity of cRaf/ERK1/2 were observed. Thus, we demonstrated that the process of neurogenesis fading during HU begins with inhibition of the formation of immature neurons and associated ERK1/2 signaling activity, while DFS prevents the development of mentioned alterations.

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Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice

Nature Communications ◽

10.1038/ncomms11773 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 36

Author(s):

Hongsheng Zhang ◽

Eunchai Kang ◽

Yaqing Wang ◽

Chaojuan Yang ◽

Hui Yu ◽

...

Keyword(s):

Neuronal Development ◽

Synapse Formation ◽

Critical Role ◽

Memory Loss ◽

Long Term Potentiation ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Mammalian Brain ◽

Neural Function

AbstractSeveral genome- and proteome-wide studies have associated transcription and translation changes ofCRMP2(collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brainin vivo. Here we show that brain-specificCrmp2knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss ofCrmp2in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown ofcrmp2specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

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Effects and Potential Mechanisms of Alcohol Use Disorder on the Fate Determination of Newly Born Neurons in the Hippocampus

Alcohol and Alcoholism ◽

10.1093/alcalc/agaa083 ◽

2020 ◽

Vol 55 (6) ◽

pp. 598-602

Author(s):

Zahra Shabani ◽

Mohsen Jafarzadeh Gharehziaaddin

Keyword(s):

Hippocampal Neurogenesis ◽

Adult Brain ◽

Adult Hippocampal Neurogenesis ◽

Mammalian Brain ◽

Extrinsic Factors ◽

Proliferation And Differentiation ◽

Underlying Mechanisms

Abstract In the adult mammalian brain, new functional neurons are generated throughout life because of sustained proliferation and differentiation of neural stem cells (NSCs). The subventricular zone (SVZ), lining the lateral ventricle, and the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus are the two major neurogenic regions in the adult brain. This process is not fixed but is highly modulated by numerous intrinsic and extrinsic factors. Neurogenesis has become in the focus of interest for its involvement in repairing the damaged brain and this motivates researchers to detect controlling mechanisms of this process. Recent evidence suggests that alcohol usage can directly influence adult hippocampal neurogenesis, but its mechanisms remain a matter for debate. Thus, this review summarizes in vivo/in vitro studies on the role of alcohol in hippocampal neurogenesis during adulthood and clarifies its underlying mechanisms by highlighting neurotransmitters and their receptors.

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Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1514652113 ◽

2016 ◽

Vol 113 (18) ◽

pp. E2536-E2545 ◽

Cited By ~ 54

Author(s):

Jonathan Moss ◽

Elias Gebara ◽

Eric A. Bushong ◽

Irene Sánchez-Pascual ◽

Ruadhan O’Laoi ◽

...

Keyword(s):

Stem Cells ◽

Dentate Gyrus ◽

Radial Glia ◽

Molecular Layer ◽

Cell Activity ◽

Local Environment ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Granule Cell Layer ◽

Neurogenic Niche

Adult hippocampal neurogenesis relies on the activation of neural stem cells in the dentate gyrus, their division, and differentiation of their progeny into mature granule neurons. The complex morphology of radial glia-like (RGL) stem cells suggests that these cells establish numerous contacts with the cellular components of the neurogenic niche that may play a crucial role in the regulation of RGL stem cell activity. However, the morphology of RGL stem cells remains poorly described. Here, we used light microscopy and electron microscopy to examine Nestin-GFP transgenic mice and provide a detailed ultrastructural reconstruction analysis of Nestin-GFP–positive RGL cells of the dentate gyrus. We show that their primary processes follow a tortuous path from the subgranular zone through the granule cell layer and ensheathe local synapses and vasculature in the inner molecular layer. They share the ensheathing of synapses and vasculature with astrocytic processes and adhere to the adjacent processes of astrocytes. This extensive interaction of processes with their local environment could allow them to be uniquely receptive to signals from local neurons, glia, and vasculature, which may regulate their fate.

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