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

Shtaya, Anan, Sadek, Ahmed-Ramadan, Zaben, Malik ORCID:, Seifert, Gerald, Pringle, Ashley, Steinhäuser, Christian and Gray, William Peter ORCID: 2018. AMPA receptors and seizures mediate hippocampal radial glia-like stem cell proliferation. GLIA 66 (11) , pp. 2397-2413. 10.1002/glia.23479

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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. GFAP-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 BrdU pre-labelled 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 invitro. 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
Date Type: Publication
Status: Published
Schools: Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Wiley
ISSN: 0894-1491
Date of First Compliant Deposit: 25 July 2018
Date of Acceptance: 4 June 2018
Last Modified: 11 Nov 2023 03:00

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