Antisense oligonucleotide to GABA(A) receptor gamma2 subunit induces limbic status epilepticus.

Abstract:

:Gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. A deficiency of GABAergic inhibition mediated via the GABAA receptor complex has for a long time been suspected to be a central factor in epileptogenesis. Status epilepticus is a condition of sustained and prolonged excitation of neuronal circuits, as detected by epileptiform discharges in the electroencephalogram (EEG). Reduction of GABAA receptor-mediated hippocampal inhibition has been implicated in the development of status epilepticus. The present study provides direct evidence of a link between the GABAA receptor and epilepsy. We show that selective inhibition of the expression of the GABAA receptor gamma2 subunit in the rat hippocampus by means of antisense oligonucleotides leads to spontaneous electrographic seizures that evolve into profound limbic status epilepticus, ultimately resulting in severe neurodegenerative changes. Concurrent treatment with diazepam prevents the development of status epilepticus and markedly reduces neuronal cell loss. These findings strongly support the hypothesis that the GABAA receptor is critically involved in the pathogenesis of seizures and status epilepticus.

journal_name

J Neurosci Res

authors

Karle J,Woldbye DP,Elster L,Diemer NH,Bolwig TG,Olsen RW,Nielsen M

doi

10.1002/(SICI)1097-4547(19981215)54:6<863::AID-JNR

subject

Has Abstract

pub_date

1998-12-15 00:00:00

pages

863-9

issue

6

eissn

0360-4012

issn

1097-4547

pii

10.1002/(SICI)1097-4547(19981215)54:6<863::AID-JNR

journal_volume

54

pub_type

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