Universität zu Köln

Foerstera, Benjamin, Belaidi, Abdel Ali, Juettner, Rene, Bernert, Carola, Tsokos, Michael, Lehmann, Thomas-N., Horn, Peter, Dehnicke, Christoph, Schwarz, Guenter ORCID: 0000-0002-2118-9338 and Meier, Jochen C. (2010). Irregular RNA splicing curtails postsynaptic gephyrin in the cornu ammonis of patients with epilepsy. Brain, 133. S. 3778 - 3795. OXFORD: OXFORD UNIV PRESS. ISSN 0006-8950

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Abstract

Anomalous hippocampal inhibition is involved in temporal lobe epilepsy, and reduced gephyrin immunoreactivity in the temporal lobe epilepsy hippocampus has been reported recently. However, the mechanisms responsible for curtailing postsynaptic gephyrin scaffolds are poorly understood. Here, we have investigated gephyrin expression in the hippocampus of patients with intractable temporal lobe epilepsy. Immunohistochemical and western blot analyses revealed irregular gephyrin expression in the cornu ammonis of patients with temporal lobe epilepsy and four abnormally spliced gephyrins lacking several exons in their G-domains were isolated. Identified temporal lobe epilepsy gephyrins have oligomerization deficits and they curtail hippocampal postsynaptic gephyrin and GABA(A) receptor alpha 2 while interacting with regularly spliced gephyrins. We found that cellular stress (alkalosis and hyperthermia) induces exon skipping in gephyrin messenger RNA, which is responsible for curtailed postsynaptic gephyrin and GABA(A) receptor alpha 2 scaffolds. Accordingly, we did not obtain evidence for gephyrin gene mutations in patients with temporal lobe epilepsy. Cellular stress such as alkalosis, for example arising from seizure activity, could thus facilitate the development of temporal lobe epilepsy by reducing GABA(A) receptor alpha 2-mediated hippocampal synaptic transmission selectively in the cornu ammonis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Foerstera, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Belaidi, Abdel Ali UNSPECIFIED UNSPECIFIED UNSPECIFIED Juettner, Rene UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernert, Carola UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsokos, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Thomas-N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Horn, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Dehnicke, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Guenter UNSPECIFIED orcid.org/0000-0002-2118-9338 UNSPECIFIED Meier, Jochen C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-491167
DOI:	10.1093/brain/awq298
Journal or Publication Title:	Brain
Volume:	133
Page Range:	S. 3778 - 3795
Date:	2010
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	0006-8950
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TEMPORAL-LOBE EPILEPSY; GABA(A) RECEPTOR SUBTYPES; GABAERGIC SYNAPTIC-TRANSMISSION; GLYCINE RECEPTOR; HIPPOCAMPAL-NEURONS; TONIC INHIBITION; INTRACELLULAR PH; MOUSE MODEL; SYNAPSES; RAT Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49116