Increased Expression of GABAA Receptor β-Subunits in the Hippocampus of Patients with Temporal Lobe Epilepsy

• Published in: Journal of neuropathology and experimental neurology Vol. 62; no. 8; pp. 820 - 834
• Main Authors: PIRKER, SUSANNE, SCHWARZER, CHRISTOPH, CZECH, THOMAS, BAUMGARTNER, CHRISTOPH, POCKBERGER, HELMUT, MAIER, HANS, HAUER, BIRGIT, SIEGHART, WERNER, FURTINGER, SABINE, SPERK, GÜNTHER
• Format: Journal Article
• Language: English
• Published: American Association of Neuropathologists, Inc 01-08-2003
• ISSN: 0022-3069; 1554-6578

It has been postulated that dysfunction of the GABA-ergic transmission is causatively related to the development of epilepsy. Animal models of temporal lobe epilepsy (TLE) revealed considerable changes in the expression of GABAA receptor subunits in the hippocampus. Using immunocytochemistry, we investigated the expression of GABAA receptor subunits α1, α3, β1–3, and γ2 in hippocampal specimens obtained at surgery from TLE patients with and without hippocampal sclerosis and in autopsy controls. Consistent with the severe neurodegeneration in the CA1 sector, significant decreases in α1-, α3-, β3-, and γ2-subunit immunoreactivity (IR) were detected in sclerotic but not in nonsclerosic specimens. In contrast, pronounced increases in IR of all 3 β-subunits were observed in most sectors of the hippocampal formation both in sclerotic and nonsclerotic specimens, being especially pronounced in the dentate molecular layer and in the subiculum where subunit α3- and γ2-IR were also elevated. Using in situ hybridization for subunits β2 and β3, increased expression of the respective mRNAs was detected in dentate granule cells of patients with and without hippocampal sclerosis. β-subunits are important constituents of the GABAA receptor and contribute to the binding site of GABA. Our data indicate pronounced adaptive changes in the expression of these GABAA receptor subunits related to seizure activity and indicate altered assembly of GABAA receptors in TLE.