GABAB receptor autoradiography in hippocampal sclerosis associated with human temporal lobe epilepsy

A Billinton, VH Baird, M Thom, JS Duncan, N Upton, Norman Bowery

Research output: Contribution to journalArticle

23 Citations (Scopus)

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:
Original languageEnglish
Pages (from-to)475-480
Number of pages6
JournalBritish Journal of Pharmacology
Volume132
DOIs
Publication statusPublished - 1 Jan 2001

Keywords

  • receptor autoradiography
  • temporal lobe epilepsy
  • hippocampal sclerosis
  • GABA(B)

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