Abstracts

GABAA receptors are the most abundant inhibitory neurotransmitter receptors in forebrain, and many studies indicate that alterations in these receptors may play an important role in epileptogenesis. Previous studies from our laboratory found alterations in GABA receptor function and gene expression in dentate gyrus (DG) following pilocarpine-induced seizures. In the present study we aimed at studying the effect of early-life seizures on GABAA receptors in different areas of hippocampus such as CA1, CA3 and DG and compare the changes in two different models of temporal lobe epilepsy. Twenty days old rat pups (P20) were subjected to pilocarpine or KA induced status epilepticus (SE). Seven days after SE induction, rats were sacrificed and using antisense RNA amplification (aRNA) technique expression of 16 different GABAAR subunit mRNAs was examined in acutely dissected DG, CA1 and CA3. Total GABAAR subunit mRNA expression was increased 3 fold in DG, 2 fold in CA1 and 1.5 fold in CA3 in Pilocarpine-injected rats and increased 2 fold in DG, decreased 1.5 fold in CA1 and no change in CA3 in KA-injected rats as compared to control rats. GABAAR subunits [alpha]1, [alpha]2, [beta]1, [epsilon] were increased in DG in both KA and Pilocarpine group of rats. Levels of [alpha]2, [alpha]6, [beta]1, [epsilon] were decreased in CA1, whereas levels of [alpha]2, [alpha]6, [beta]2, [epsilon] was increased in CA3 in KA-injected rats. Level of [alpha]2 in CA3 and level of [beta]2 in CA1 were increased in pilocarpine-injected rats. The alterations in GABAAR subunit mRNA expression in DG were identical in the KA and Pilocarpine-models, but subunit expression differed between models in CA1 and CA3 regions. These findings suggest that acute changes of GABA receptor subunit mRNA expression in DG after both KA and Pilocarpine-induced SE may play a similar role in epileptogenesis in immature rat. However, changes in GABA receptor subunit mRNA expression in CA1 and CA3seem to be model-dependent. (Supported by NIH NS38595 to ABK.)