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 Resjournal_title
Journal of neuroscience researchauthors
Karle J,Woldbye DP,Elster L,Diemer NH,Bolwig TG,Olsen RW,Nielsen Mdoi
10.1002/(SICI)1097-4547(19981215)54:6<863::AID-JNRsubject
Has Abstractpub_date
1998-12-15 00:00:00pages
863-9issue
6eissn
0360-4012issn
1097-4547pii
10.1002/(SICI)1097-4547(19981215)54:6<863::AID-JNRjournal_volume
54pub_type
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