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Kainate enhances hippocampal precursor cell proliferation and survival in vitro, while Kainate induced seizures additionally recruits quiescent progenitors in vivo

Kainate enhances hippocampal precursor cell proliferation and survival in vitro, while Kainate induced seizures additionally recruits quiescent progenitors in vivo
Kainate enhances hippocampal precursor cell proliferation and survival in vitro, while Kainate induced seizures additionally recruits quiescent progenitors in vivo
It is widely accepted that hippocampal neurogenesis persists throughout life and is altered by acute seizures. Kainate is often used to model temporal lobe epilepsy and hippocampal damage. Kainate-induced status epilepticus transiently enhances hippocampal neurogenesis but the mechanisms are not well understood. Therefore, we examined the effects of Kainate on hippocampal precursors in vitro. We also investigated the acute effects of Kainate/seizures on a pre-labelled clone of proliferating hippocampal precursors in vivo. Cultured hippocampal cells were prepared from Wistar rats P7-10 and exposed to 5µM Kainate. BrdU and Ki-67 were used to measure cell proliferation while caspase-3, Propidium iodide, MitoTracker, and Time-lapse microscopy were used to study cell survival. Nestin and TuJ1 were used to label precursor cells and neuroblasts, respectively. To examine Kainate effects in vivo, a clone of proliferating cells in the dentate gyrus was pre-labelled with BrdU 24 hours before Kainate-induced status epilepticus and examined 6-72 h later. In vitro, we found that Kainate increased the proliferation rate of nestin-positive postnatal hippocampal precursors, via AMPA receptors. It also enhanced the survival of nestin and TuJ1 cells with a proportional increase in neuroblasts. Consistently, Kainate/seizures in vivo increased cell proliferation in the subgranular zone (SGZ) and granule cell layer (GCL) of the adult dentate gyrus, without enhancing cell death. Kainate/seizures recruited un-labelled quiescent cells in the SGZ. In contrast it increased the proliferation of the pre-labelled population only in the GCL. Kainate/seizures drove significantly more BrdU+ cells to become postmitotic in the GCL but not in the SGZ. Doublecortin positive cells increased in the GCL by 72 h after Kainate. We conclude that Kainate enhances hippocampal precursor proliferation and survival without increasing cell death, while seizures recruit a quiescent cell population in the SGZ.
a-development, neurogenesis and gliogenesis, cell lineage, cell fate specification
Federation of European Neuroscience Societies (FENS)
Shtaya, A.
a8b99cef-13c3-4a43-a799-d6d13799ab2b
Pringle, A.
6339ed95-c491-43a8-b2fb-2384466dc80d
Gray, W.P.
e0ba5a65-bd74-4a4f-b640-5abf64fbb377
Shtaya, A.
a8b99cef-13c3-4a43-a799-d6d13799ab2b
Pringle, A.
6339ed95-c491-43a8-b2fb-2384466dc80d
Gray, W.P.
e0ba5a65-bd74-4a4f-b640-5abf64fbb377

Shtaya, A., Pringle, A. and Gray, W.P. (2008) Kainate enhances hippocampal precursor cell proliferation and survival in vitro, while Kainate induced seizures additionally recruits quiescent progenitors in vivo. In FENS Forum 2008. vol. 4, Federation of European Neuroscience Societies (FENS)..

Record type: Conference or Workshop Item (Paper)

Abstract

It is widely accepted that hippocampal neurogenesis persists throughout life and is altered by acute seizures. Kainate is often used to model temporal lobe epilepsy and hippocampal damage. Kainate-induced status epilepticus transiently enhances hippocampal neurogenesis but the mechanisms are not well understood. Therefore, we examined the effects of Kainate on hippocampal precursors in vitro. We also investigated the acute effects of Kainate/seizures on a pre-labelled clone of proliferating hippocampal precursors in vivo. Cultured hippocampal cells were prepared from Wistar rats P7-10 and exposed to 5µM Kainate. BrdU and Ki-67 were used to measure cell proliferation while caspase-3, Propidium iodide, MitoTracker, and Time-lapse microscopy were used to study cell survival. Nestin and TuJ1 were used to label precursor cells and neuroblasts, respectively. To examine Kainate effects in vivo, a clone of proliferating cells in the dentate gyrus was pre-labelled with BrdU 24 hours before Kainate-induced status epilepticus and examined 6-72 h later. In vitro, we found that Kainate increased the proliferation rate of nestin-positive postnatal hippocampal precursors, via AMPA receptors. It also enhanced the survival of nestin and TuJ1 cells with a proportional increase in neuroblasts. Consistently, Kainate/seizures in vivo increased cell proliferation in the subgranular zone (SGZ) and granule cell layer (GCL) of the adult dentate gyrus, without enhancing cell death. Kainate/seizures recruited un-labelled quiescent cells in the SGZ. In contrast it increased the proliferation of the pre-labelled population only in the GCL. Kainate/seizures drove significantly more BrdU+ cells to become postmitotic in the GCL but not in the SGZ. Doublecortin positive cells increased in the GCL by 72 h after Kainate. We conclude that Kainate enhances hippocampal precursor proliferation and survival without increasing cell death, while seizures recruit a quiescent cell population in the SGZ.

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More information

Published date: 2008
Additional Information: FENS Abstracts.Poster board A54 - Session 009 - Lineage Abstract n° 009.24.
Keywords: a-development, neurogenesis and gliogenesis, cell lineage, cell fate specification

Identifiers

Local EPrints ID: 70234
URI: http://eprints.soton.ac.uk/id/eprint/70234
PURE UUID: c9b6ebb3-7994-4bc2-93ba-c5fd5fbfba7f
ORCID for A. Pringle: ORCID iD orcid.org/0000-0003-2421-4380

Catalogue record

Date deposited: 22 Mar 2010
Last modified: 13 Dec 2021 02:39

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Contributors

Author: A. Shtaya
Author: A. Pringle ORCID iD
Author: W.P. Gray

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