title: GABA(B) receptor autoradiography in hippocampal sclerosis associated with human temporal lobe epilepsy.
abstract: 1. Metabotropic gamma-aminobutyric acid receptors (GABA(B)) exist both pre- and postsynaptically throughout the brain, mediating the suppression of neurotransmitter release and late inhibitory postsynaptic potentials. Investigation of GABA(B) receptors in rodent models of temporal lobe epilepsy (TLE) suggests that expression or function of these receptors may be altered in the disorder. 2. The aim of the present study was to investigate the expression of GABA(B) receptors in samples of hippocampus surgically resected from patients with hippocampal sclerosis (HS) related intractable TLE, and compare this expression with samples of neurologically normal post-mortem (PM) control hippocampal tissue. Appropriate measures of neuronal loss associated with HS were investigated for comparison with receptor binding data. 3. Receptor autoradiography with [(3)H]-GABA in the presence of isoguvacine, and quantitative densitometric analysis were used to investigate GABA(B) receptor expression (B(max)) and affinity (K(D)) in 11 HS samples and eight controls. A three-dimensional cell counting technique was used to assess neuronal density in both groups. 4. GABA(B) receptor density was significantly reduced in CA1, CA2, CA3, hilus and dentate gyrus, and increased in the subiculum, of HS cases as compared with PM controls. Neuronal loss was significant in all regions measured. When adjusted for neuronal loss, CA1 GABA(B) receptor expression appeared significantly upregulated (P:<0.05). 5. In HS/TLE, GABA(B) receptor expression per remaining neurone appears increased in CA1. This finding, and increased [(3)H]-GABA affinity at CA3 and hilar GABA(B) receptors, suggests altered GABA(B) receptor function may occur in human HS/TLE, possibly as a result of synaptic reorganization.
authors.affiliation: Department of Pharmacology, Division of Neuroscience, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT. andrew.billinton@bbsrc.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Billinton
authors.forename: V H
authors.initials: VH
authors.lastname: Baird
authors.forename: M
authors.initials: M
authors.lastname: Thom
authors.forename: J S
authors.initials: JS
authors.lastname: Duncan
authors.forename: N
authors.initials: N
authors.lastname: Upton
authors.forename: N G
authors.initials: NG
authors.lastname: Bowery
mesh_terms: D000328:Adult; D001345:Autoradiography; D002452:Cell Count; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid