Increased expression of gamma-aminobutyric acid type B receptors in the hippocampus of patients with temporal lobe epilepsy.
Malfunctioning of the GABA-ergic system has been postulated as a possible cause of epilepsy. We investigated changes in the mRNA expression of the GABA(B) receptor subtypes GABA(B)-R1 and GABA(B)-R2 and of GABA(B) receptor binding in the hippocampus of patients with temporal lobe epilepsy (TLE) compared with post-mortem controls. In patients with Ammon's horn sclerosis, significant decreases in [3H]CG54626A binding were observed in subfields CA1 and CA3 of the hippocampus proper and the dentate hilus. On the other hand, both GABA(B) receptor mRNAs and receptor binding were enhanced after correction for neuronal loss in dentate granule cells and in the molecular layer, respectively, and the subiculum of patients with and without hippocampal sclerosis. These increases were even more pronounced when correcting the values for cell losses in the respective areas and indicated also increased expression of GABA(B)-R in the dentate hilus. Increased expression of both subtypes of GABA(B) receptors indicates augmented presynaptic inhibition of glutamate release as a possible protective mechanism in TLE.
Furtinger
Sabine
S
Department of Pharmacology, University of Innsbruck, 6020 Innsbruck, Austria.
Pirker
Susanne
S
Czech
Thomas
T
Baumgartner
Christoph
C
Sperk
Günther
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018080:Receptors, GABA-B / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D018080:Receptors, GABA-B