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AMPA receptors and seizures mediate hippocampal radial glia-like stem cell proliferation.

Shtaya, A; Sadek, A-R; Zaben, M; Seifert, G; Pringle, A; Steinhäuser, C; Gray, WP (2018) AMPA receptors and seizures mediate hippocampal radial glia-like stem cell proliferation. Glia, 66 (11). pp. 2397-2413. ISSN 1098-1136 https://doi.org/10.1002/glia.23479
SGUL Authors: Shtaya, Anan BY

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Abstract

Neurogenesis is sustained throughout life in the mammalian brain, supporting hippocampus-dependent learning and memory. Its permanent alteration by status epilepticus (SE) is associated with learning and cognitive impairments. The mechanisms underlying the initiation of altered neurogenesis after SE are not understood. Glial fibrillary acidic protein-positive radial glia (RG)-like cells proliferate early after SE, but their proliferation dynamics and signaling are largely unclear. We have previously reported a polarized distribution of AMPA receptors (AMPARs) on RG-like cells in vivo and postulated that these may signal their proliferation. Here, we examined the acute effects of kainate on hippocampal precursor cells in vitro and in kainate-induced SE on proliferating and quiescent clones of 5-bromo-2-deoxyuridine prelabeled hippocampal precursors in vivo. In vitro, we found that 5 μM kainate shortened the cell cycle time of RG-like cells via AMPAR activation and accelerated cell cycle re-entry of their progeny. It also shifted their fate choice expanding the population of RG-like cells and reducing the population of downstream amplifying neural progenitors. Kainate enhanced the survival of all precursor cell subtypes. Pharmacologically, kainate's proliferative and survival effects were abolished by AMPAR blockade. Functional AMPAR expression was confirmed on RG-like cells in vitro. In agreement with these observations, kainate/seizures enhanced the proliferation and expansion predominantly of constitutively cycling RG-like cell clones in vivo. Our results identify AMPARs as key potential players in initiating the proliferation of dentate RG-like cells and unravel a possible receptor target for modifying the radial glia-like cell response to SE.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Shtaya, A, Sadek, A‐R, Zaben, M, et al. AMPA receptors and seizures mediate hippocampal radial glia‐like stem cell proliferation. Glia. 2018; 66: 2397– 2413, which has been published in final form at https://doi.org/10.1002/glia.23479. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Keywords: AMPARs, Kainate, epilepsy, precursors, radial glia-like, rat, Animals, Animals, Newborn, Benzodiazepines, Cell Death, Cell Proliferation, Cells, Cultured, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Hippocampus, Kainic Acid, Ki-67 Antigen, Male, Membrane Potentials, Nerve Tissue Proteins, Neuroglia, Quinoxalines, Rats, Rats, Wistar, Receptors, AMPA, Seizures, Stem Cells, Hippocampus, Neuroglia, Cells, Cultured, Stem Cells, Animals, Animals, Newborn, Rats, Rats, Wistar, Seizures, Kainic Acid, Benzodiazepines, Quinoxalines, Receptors, AMPA, Nerve Tissue Proteins, Ki-67 Antigen, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Cell Death, Cell Proliferation, Membrane Potentials, Male, AMPARs, epilepsy, Kainate, precursors, radial glia-like, rat, AMPARs, Kainate, epilepsy, precursors, radial glia-like, rat, 1109 Neurosciences, Neurology & Neurosurgery
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Glia
ISSN: 1098-1136
Language: eng
Dates:
DateEvent
30 November 2018Published
25 October 2018Published Online
4 June 2018Accepted
Projects:
Project IDFunderFunder ID
G0801418Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/L010305/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0300356Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 30357924
Web of Science ID: WOS:000451832700010
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110339
Publisher's version: https://doi.org/10.1002/glia.23479

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