GABA(B1a), GABA(B1b) AND GABA(B2) mRNA variants expression in hippocampus resected from patients with temporal lobe epilepsy

• Published in: Neuroscience Vol. 122; no. 4; pp. 975 - 984
• Main Authors: Princivalle, A P, Duncan, J S, Thom, M, Bowery, N G
• Format: Journal Article
• Language: English
• Published: United States 2003
• Subjects: Adult; Aged; Aged, 80 and over; Epilepsy, Temporal Lobe - genetics; Epilepsy, Temporal Lobe - metabolism; Epilepsy, Temporal Lobe - pathology; Female; Gene Expression Regulation - physiology; Genetic Variation - physiology; Hippocampus - metabolism; Hippocampus - pathology; Humans; Male; Middle Aged; Protein Isoforms - biosynthesis; Protein Isoforms - genetics; Receptors, GABA - biosynthesis; Receptors, GABA - genetics; Receptors, GABA-B - biosynthesis; Receptors, GABA-B - genetics; RNA, Messenger - biosynthesis; RNA, Messenger - genetics
• ISSN: 0306-4522
• DOI: 10.1016/j.neuroscience.2003.08.044

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.