Contribution of aberrant GluK2-containing kainate receptors to chronic seizures in temporal lobe epilepsy.
Cell Reports. 2014-07-01; 8(2): 347-354
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1. Cell Rep. 2014 Jul 24;8(2):347-54. doi: 10.1016/j.celrep.2014.06.032. Epub 2014
Contribution of aberrant GluK2-containing kainate receptors to chronic seizures
in temporal lobe epilepsy.
Peret A(1), Christie LA(1), Ouedraogo DW(1), Gorlewicz A(2), Epsztein J(1), Mulle
C(2), Crépel V(3).
(1)INSERM, INMED, U901, 13009 Marseille, France; Aix-Marseille Université, UMR
901, 13009 Marseille, France.
(2)Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of
Bordeaux, 33000 Bordeaux, France.
(3)INSERM, INMED, U901, 13009 Marseille, France; Aix-Marseille Université, UMR
901, 13009 Marseille, France. Electronic address: .
Kainate is a potent neurotoxin known to induce acute seizures. However, whether
kainate receptors (KARs) play any role in the pathophysiology of temporal lobe
epilepsy (TLE) is not known. In TLE, recurrent mossy fiber (rMF) axons form
abnormal excitatory synapses onto other dentate granule cells that operate via
KARs. The present study explores the pathophysiological implications of KARs in
generating recurrent seizures in chronic epilepsy. In an in vitro model of TLE,
seizure-like activity was minimized in mice lacking the GluK2 subunit, which is a
main component of aberrant synaptic KARs at rMF synapses. In vivo, the frequency
of interictal spikes and ictal discharges was strongly reduced in GluK2(-/-) mice
or in the presence of a GluK2/GluK5 receptor antagonist. Our data show that
aberrant GluK2-containing KARs play a major role in the chronic seizures that
characterize TLE and thus constitute a promising antiepileptic target.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
PMID: 25043179 [Indexed for MEDLINE]