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

Abstract

1. Metabotropic γ-aminobutyric acid receptors (GABAB) exist both pre- and postsynaptically throughout the brain, mediating the suppression of neurotransmitter release and late inhibitory postsynaptic potentials. Investigation of GABAB 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 GABAB 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 [3H]-GABA in the presence of isoguvacine, and quantitative densitometric analysis were used to investigate GABAB receptor expression (Bmax) and affinity (KD) in 11 HS samples and eight controls. A three-dimensional cell counting technique was used to assess neuronal density in both groups. 4. GABAB 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 GABAB receptor expression appeared significantly upregulated (P<0.05). 5. In HS/TLE, GABAB receptor expression per remaining neurone appears increased in CA1. This finding, and increased [3H]-GABA affinity at CA3 and hilar GABAB receptors, suggests altered GABAB receptor function may occur in human HS/TLE, possibly as a result of synaptic reorganization.