GABAB1a, GABAB1b AND GABAB2 mRNA variants expression in hippocampus resected from patients with temporal lobe epilepsy

The aim of this study was to investigate the mRNA expression of the two GABAB1 receptor isoforms and the GABAB2 subunit, in human postmortem control hippocampal sections and in sections resected from epilepsy patients using quantitative in situ hybridisation autoradiography. Utilising human control hippocampal sections it was shown that the oligonucleotides employed were specific to the receptor. Hippocampal slices from surgical specimens obtained from patients with hippocampal sclerosis and temporal lobe epilepsy were compared with neurologically normal postmortem control subjects for neuropathology and GABAB mRNA expression. Neuronal loss was observed in most of the hippocampal subregions, but in the subiculum no significant difference was detected. The localisation of GABAB1a and GABAB1b isoform mRNAs in human control hippocampal sections supported and extended earlier studies using the GABAB1 pan probe, which does not distinguish between the two GABAB1 isoforms. Moreover, the GABAB2 mRNA location confirmed the heterodimerisation of the receptor. Thus, although there was an apparent correlation between GABAB1b and GABAB2, GABAB1a exhibited no such relationship. GABAB1b and GABAB2 showed a similar intensity of expression whilst GABAB1a displayed a lower hybridisation signal. Comparison of the expression of the three mRNAs between control and epileptic subjects showed significant decreases or increases in different hippocampal subregions. GABAB isoforms and subunit mRNA expression per remaining neuron was significantly increased in the hilus and dentate gyrus. These results demonstrate that altered GABAB receptor mRNA expression occurs in human TLE; possibly the observed changes may also serve to counteract ongoing hyperexcitability.