Epigenetic Regulation in the Neurogenic Niche of the Adult Dentate Gyrus

2021 ◽  
pp. 136343
Author(s):  
Ryan N. Sheehy ◽  
Luis J. Quintanilla ◽  
Juan Song
Keyword(s):  
Dentate Gyrus ◽  
Epigenetic Regulation ◽  
Neurogenic Niche

scholarly journals Adult neural stem cells have latent inflammatory potential that is kept suppressed by Tcf4 to facilitate adult neurogenesis

2021 ◽  
Vol 7 (21) ◽  
pp. eabf5606
Author(s):  
Mohammad Shariq ◽  
Vinaya Sahasrabuddhe ◽  
Sreevatsan Krishna ◽  
Swathi Radha ◽  
Nruthyathi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Neural Progenitors ◽  
The Other ◽  
Proliferative Capacity ◽  
Differentiation Potential ◽  
Neurogenic Niche ◽  
Transcription Factor 4

Inflammation is known to adversely affect adult neurogenesis, wherein the source of inflammation is largely thought to be extraneous to the neurogenic niche. Here, we demonstrate that the adult hippocampal neural progenitors harbor an inflammatory potential that is proactively suppressed by transcription factor 4 (Tcf4). Deletion of Tcf4 in hippocampal nestin-expressing progenitors causes loss of proliferative capacity and acquisition of myeloid inflammatory properties. This transformation abolishes their differentiation potential and causes production of detrimental factors that adversely affect niche cells, causing inflammation in the dentate gyrus. Thus, on one hand, Tcf4 deletion causes abrogation of proliferative progenitors leading to reduction of adult neurogenesis, while on the other, their accompanying inflammatory transformation inflicts inflammation in the niche. Taken together, we provide the first evidence for a latent inflammatory potential of adult hippocampal neural progenitors and identify Tcf4 as a critical regulator that facilitates adult neurogenesis via proactive suppression of this detrimental potential.

scholarly journals Enduring Effects of Conditional Brain Serotonin Knockdown, Followed by Recovery, on Adult Rat Neurogenesis and Behavior

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3240
Author(s):  
Maria Sidorova ◽  
Golo Kronenberg ◽  
Susann Matthes ◽  
Markus Petermann ◽  
Rainer Hellweg ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Tryptophan Hydroxylase ◽  
Transgenic Rat ◽  
Compensatory Mechanism ◽  
Shrna Expression ◽  
Neurogenic Niche ◽  
Adult Rat ◽  
And Behavior ◽  
Transgenic Rat Model ◽  
Antidepressant Action

Serotonin (5-hydroxytryptamine, 5-HT) is a crucial signal in the neurogenic niche of the hippocampus, where it is involved in antidepressant action. Here, we utilized a new transgenic rat model (TetO-shTPH2), where brain 5-HT levels can be acutely altered based on doxycycline (Dox)-inducible shRNA-expression. On/off stimulations of 5-HT concentrations might uniquely mirror the clinical course of major depression (e.g., relapse after discontinuation of antidepressants) in humans. Specifically, we measured 5-HT levels, and 5-HT metabolite 5-HIAA, in various brain areas following acute tryptophan hydroxylase 2 (Tph2) knockdown, and replenishment, and examined behavior and proliferation and survival of newly generated cells in the dentate gyrus. We found that decreased 5-HT levels in the prefrontal cortex and raphe nuclei, but not in the hippocampus of TetO-shTPH2 rats, lead to an enduring anxious phenotype. Surprisingly, the reduction in 5-HT synthesis is associated with increased numbers of BrdU-labeled cells in the dentate gyrus. At 3 weeks of Tph2 replenishment, 5-HT levels return to baseline and survival of newly generated cells is unaffected. We speculate that the acutely induced decrease in 5-HT concentrations and increased neurogenesis might represent a compensatory mechanism.

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

2016 ◽  
Vol 113 (18) ◽  
pp. E2536-E2545 ◽  
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.

scholarly journals Stereological characterization of neurogenic niche secretory cell types in the mouse dorsal dentate gyrus

2019 ◽  
Author(s):  
Joshua D. Rieskamp ◽  
Patricia Sarchet ◽  
Bryon M. Smith ◽  
Elizabeth D. Kirby
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Dentate Gyrus ◽  
Cell Density ◽  
Adult Neurogenesis ◽  
Secretory Cell ◽  
Cell Types ◽  
Cell Populations ◽  
Neurogenic Niche ◽  
Adult Mice

AbstractAdult neurogenesis in the dorsal dentate gyrus (DG) subregion of the mammalian hippocampus supports critical cognitive processes related to memory. Local DG cell populations form a neurogenic niche specialized to regulate adult neurogenesis. Recently, DG astrocytes, microglia, endothelia, and neural stem cells have been identified as sources of neurogenesismodulating secreted factors. Accurately estimating the size of these cell populations is useful for elucidating their relative contributions to niche physiology. Previous studies have characterized these cell types individually, but to our knowledge no comprehensive study of all these cell types exists. This is problematic because considerable variability in reported population size complicates comparisons across studies. Here, we apply consistent stereological methods within a single study to estimate cell density for neurogenesis-modulating secretory cell types in the dorsal DG of adult mice. We used immunohistochemical phenotypic markers to quantify cell density and found that stellate astrocytes were the most numerous followed by endothelia, intermediate progenitors, microglia, and neural stem cells. We did not observe any significant sex differences in cell density. We expect our data will facilitate efforts to elucidate the role of DG secretory cell populations in regulating adult neurogenesis.

scholarly journals Epigenetic Regulation by Chromatin Activation Mark H3K4me3 in Primate Progenitor Cells within Adult Neurogenic Niche

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Richard S. Sandstrom ◽  
Michael R. Foret ◽  
Douglas A. Grow ◽  
Eric Haugen ◽  
Christopher T. Rhodes ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Epigenetic Regulation ◽  
Neurogenic Niche ◽  
Chromatin Activation

Malfunctional Reorganization in the Developing Limbo-Prefrontal System in Animals: Implications for Human Psychoses?

2001 ◽  
Vol 12 (1) ◽  
pp. 8-14
Author(s):  
Gertraud Teuchert-Noodt ◽  
Ralf R. Dawirs
Keyword(s):  
Prefrontal Cortex ◽  
Mental Disorders ◽  
Dentate Gyrus ◽  
Cognitive Functions ◽  
Experimental Approach ◽  
Regulatory Mechanisms ◽  
Hippocampal Dentate Gyrus ◽  
Non Invasive ◽  
Invasive Method ◽  
Activity Dependent

Abstract: Neuroplasticity research in connection with mental disorders has recently bridged the gap between basic neurobiology and applied neuropsychology. A non-invasive method in the gerbil (Meriones unguiculus) - the restricted versus enriched breading and the systemically applied single methamphetamine dose - offers an experimental approach to investigate psychoses. Acts of intervening affirm an activity dependent malfunctional reorganization in the prefrontal cortex and in the hippocampal dentate gyrus and reveal the dopamine position as being critical for the disruption of interactions between the areas concerned. From the extent of plasticity effects the probability and risk of psycho-cognitive development may be derived. Advance may be expected from insights into regulatory mechanisms of neurogenesis in the hippocampal dentate gyrus which is obviously to meet the necessary requirements to promote psycho-cognitive functions/malfunctions via the limbo-prefrontal circuit.

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