Abstracts

Studies have shown that [italic]status epilepticus[/italic] (SE) increases neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) in adult rat. It has been hypothesised that the newly generated neurons contribute to the abnormal reorganisation of the hippocampal circuitry and the development of chronic epilepsy. Moreover, increasing evidence suggests that massive glutamate release, as occurs during SE, play an important role in the regulation of neurogenesis. The goal of the present study was to investigate the effects of a selective antagonist of group I metabotropic glutamate receptors (mGluRs), 1-aminoindan-1,5-dicarboxylic acid (AIDA), on neurogenesis in the kainic acid (KA) model of temporal lobe epilepsy. SE was induced in adult male rats by intraperitoneal (i.p.) injection of KA. One group of rats received two doses of KA (8.0 mg/kg, i.p.) given at one-hour interval. Another group received a double dose of KA and AIDA (1.8 mg/kg, i.p.) and control groups received either AIDA alone (A) or saline (S) solution. The rats were monitored daily, for two hours a day, over a period of 45 consecutive days in order to observe the occurrence of spontaneous recurrent seizures (SRS). In order to assess neurogenesis, five rats of each experimental and control groups received, at different time points (7, 14 and 56 days) post-SE, two injections of 5-bromodeoxyuridine (BrdU, 50 mg/kg i.p.) within a two-hour interval and were sacrificed 24 hr later for immunohistochemical treatment. Seven days post-SE, the KA rats showed a 4-fold increase in the number of BrdU-positive cells in the SGZ compared to control rats (p[lt]0.001) and a 9-fold increase compared to KA+AIDA rats (p[lt]0.001). No difference was observed between the KA+AIDA and control rats, suggesting that AIDA reduced abnormal neurogenesis at this time point. Fourteen and 56 days post-SE, the number of BrdU-positive cells in the SGZ of the KA rats returned to control levels. The AIDA-treated rats also showed significantly less frequent SRS compared to KA-treated rats (p[lt]0.001). The results showed that KA-induced SE increased the process of neurogenesis in the adult rat and that AIDA was able to reduce the process. Overall the results suggest that mGluRs I are involved in adult neurogenesis and blocking this mechanism might play a significant role in preventing epileptogenesis in adult rats. (Supported by Savoy Fundation.)