The aim of this study was to investigate the
mRNA expression of the two
GABA(B1) receptor
isoforms and the
GABA(B2) 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
GABA(B)
mRNA expression. Neuronal loss was observed in most of the hippocampal subregions, but in the subiculum no significant difference was detected. The localisation of
GABA(B1a) and
GABA(B1b)
isoform mRNAs in human control hippocampal sections supported and extended earlier studies using the
GABA(B1) pan probe, which does not distinguish between the two
GABA(B1)
isoforms. Moreover, the
GABA(B2)
mRNA location confirmed the heterodimerisation of the receptor. Thus, although there was an apparent correlation between
GABA(B1b) and
GABA(B2),
GABA(B1a) exhibited no such relationship.
GABA(B1b) and
GABA(B2) showed a similar intensity of expression whilst
GABA(B1a) 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.
GABA(B)
isoforms and subunit
mRNA expression per remaining neuron was significantly increased in the hilus and dentate gyrus. These results demonstrate that altered
GABA(B) receptor mRNA expression occurs in human TLE; possibly the observed changes may also serve to counteract ongoing hyperexcitability.