Increased expression of GABA(A) receptor beta-subunits in the hippocampus of patients with temporal lobe epilepsy.
It has been postulated that dysfunction of the GABA-ergic transmission is causatively related to the development of epilepsy. Animal models of temporal lobe epilepsy (TLE) revealed considerable changes in the expression of GABA(A) receptor subunits in the hippocampus. Using immunocytochemistry, we investigated the expression of GABA(A) receptor subunits alpha1, alpha3, beta1-3, and gamma2 in hippocampal specimens obtained at surgery from TLE patients with and without hippocampal sclerosis and in autopsy controls. Consistent with the severe neurodegeneration in the CA1 sector, significant decreases in alpha1-, alpha3-, beta3-, and gamma2-subunit immunoreactivity (IR) were detected in sclerotic but not in nonsclerosic specimens. In contrast, pronounced increases in IR of all 3 beta-subunits were observed in most sectors of the hippocampal formation both in sclerotic and nonsclerotic specimens, being especially pronounced in the dentate molecular layer and in the subiculum where subunit alpha3- and gamma2-IR were also elevated. Using in situ hybridization for subunits beta2 and beta3, increased expression of the respective mRNAs was detected in dentate granule cells of patients with and without hippocampal sclerosis. Beta-subunits are important constituents of the GABA(A) receptor and contribute to the binding site of GABA. Our data indicate pronounced adaptive changes in the expression of these GABA(A) receptor subunits related to seizure activity and indicate altered assembly of GABA(A) receptors in TLE.
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D002675:Child, Preschool; D003720:Densitometry / Q000295:instrumentation / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D012598:Sclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology
D021122:Protein Subunits; D011963:Receptors, GABA-A; D010751:Phosphopyruvate Hydratase