GABA(B(1)) mRNA expression in hippocampal sclerosis associated with human temporal lobe epilepsy.
GABA(B) receptors act to inhibit neurotransmitter release from presynaptic terminals, and mediate the late inhibitory postsynaptic potential. Studies of GABA(B) receptor function in rodent models of temporal lobe epilepsy (TLE) suggest that GABA(B) receptor expression and/or function may be perturbed. GABA(B(1)) mRNA levels were investigated in 10 hippocampal resection samples obtained at surgery from intractable hippocampal sclerosis (HS) associated TLE patients and five neurologically normal post-mortem (PM) control samples. In situ hybridisation with a 35S-dATP-labelled oligonucleotide was carried out to measure mRNA levels, along with three-dimensional cell counting, for assessment of neuronal density in hippocampal subregions. GABA(B(1)) mRNA was significantly up-regulated in the subiculum of HS samples as compared with PM controls. When adjusted for the characteristic neuronal density changes observed in HS, GABA(B(1)) mRNA was significantly up-regulated in CA1, hilus and dentate gyrus granule cell layer of HS samples as compared with PM controls. The possibility of increased GABA(B(1)) expression suggests that changes in GABA(B) receptor mechanisms may be involved in the pathogenesis of human HS-associated TLE.
Billinton
A
A
Department of Pharmacology, Division of Neuroscience, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, B15 2TT, Birmingham, UK. andrew.billinton@bbsrc.ac.uk
Baird
V H
VH
Thom
M
M
Duncan
J S
JS
Upton
N
N
Bowery
N G
NG
D000328:Adult; D002452:Cell Count; D004833:Epilepsy, Temporal Lobe / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D018080:Receptors, GABA-B / Q000235:genetics*; D012598:Sclerosis
D012333:RNA, Messenger; D018080:Receptors, GABA-B