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Altered expression of 3-containing GABAA receptors in the neocortex of patients with focal epilepsy


Loup, F; Picard, F; Andre, V M; Kehrli, P; Yonekawa, Y; Wieser, H G; Fritschy, J M (2006). Altered expression of 3-containing GABAA receptors in the neocortex of patients with focal epilepsy. Brain : a journal of neurology, 129(12):3277-3289.

Abstract

Impaired transmission in GABAergic circuits is thought to contribute to the pathogenesis of epilepsy. Although it is well established that major reorganization of GABAA receptor subtypes occurs in the hippocampus of patients with medically refractory temporal lobe epilepsy (TLE), it is unclear whether this disorder is also associated with alterations in GABAA receptor subtypes in the neocortex. Here we have investigated immunohistochemically the subunit composition and neocortical distribution of three major GABAA receptor subtypes using antibodies specifically recognizing the subunits α1, α2, α3, β2/3 and γ2. Cortical tissue was obtained at surgery from patients with TLE and hippocampal sclerosis (HS; n = 9), TLE associated with neocortical lesions (non-HS; n = 12) and frontal lobe epilepsy (FLE; n = 5), with post-mortem samples serving as controls (n = 4). A distinct laminar and neuronal expression pattern of the α-subunit variants was found across the neocortical regions examined in the temporal and frontal lobes in both control and patient tissue samples. In the five patients with FLE, GABAA receptor subunit staining was unchanged as compared to controls. In patients with TLE we observed a marked decrease in α3-subunit staining in the superficial neocortical layers (I-III), but no change in the deep layers (V and VI) or in the expression pattern of the α1 and α2-subunits. Reduced expression in α3-containing GABAA receptors was detected in six out of nine patients of the HS group and four out of twelve patients of the non-HS group. Histopathological changes were present in eight out of the ten patients with decreased α3-subunit staining. The selective reduction in α3-containing GABAA receptors was confirmed using semiquantitative measurements of optical density (OD). The specific changes unique to α3-subunit expression in the superficial neocortical layers of patients with TLE suggest that this subtype is of particular significance in the reorganization of cortical GABAergic systems in focal epilepsy

Abstract

Impaired transmission in GABAergic circuits is thought to contribute to the pathogenesis of epilepsy. Although it is well established that major reorganization of GABAA receptor subtypes occurs in the hippocampus of patients with medically refractory temporal lobe epilepsy (TLE), it is unclear whether this disorder is also associated with alterations in GABAA receptor subtypes in the neocortex. Here we have investigated immunohistochemically the subunit composition and neocortical distribution of three major GABAA receptor subtypes using antibodies specifically recognizing the subunits α1, α2, α3, β2/3 and γ2. Cortical tissue was obtained at surgery from patients with TLE and hippocampal sclerosis (HS; n = 9), TLE associated with neocortical lesions (non-HS; n = 12) and frontal lobe epilepsy (FLE; n = 5), with post-mortem samples serving as controls (n = 4). A distinct laminar and neuronal expression pattern of the α-subunit variants was found across the neocortical regions examined in the temporal and frontal lobes in both control and patient tissue samples. In the five patients with FLE, GABAA receptor subunit staining was unchanged as compared to controls. In patients with TLE we observed a marked decrease in α3-subunit staining in the superficial neocortical layers (I-III), but no change in the deep layers (V and VI) or in the expression pattern of the α1 and α2-subunits. Reduced expression in α3-containing GABAA receptors was detected in six out of nine patients of the HS group and four out of twelve patients of the non-HS group. Histopathological changes were present in eight out of the ten patients with decreased α3-subunit staining. The selective reduction in α3-containing GABAA receptors was confirmed using semiquantitative measurements of optical density (OD). The specific changes unique to α3-subunit expression in the superficial neocortical layers of patients with TLE suggest that this subtype is of particular significance in the reorganization of cortical GABAergic systems in focal epilepsy

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:9 June 2006
Deposited On:09 Oct 2018 13:42
Last Modified:27 Apr 2019 07:01
Publisher:Oxford University Press
ISSN:0006-8950
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/brain/awl287
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093brainawl287 (Library Catalogue)
PubMed ID:17046856

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