Abstracts

Abnormal neurogenesis secondary to [italic]status epilepticus[/italic] (SE) is thought to be involved in epileptogenesis. Previous studies from our laboratory have shown that the use of the group I metabotropic glutamate receptor (mGluR) antagonist AIDA limits epileptogenesis and prevents SE-induced neurogenesis in the dentate gyrus and hilus. The goal of this study was therefore to explore the specific role of group I mGluR in the abnormal neurogenesis. In this study, group I mGluRs were activated by two agonists. The first agonist, ([italic]S[/italic])-3,5-dihydroxyphenylglycine (DHPG), activates both subtype 1 and 5 of the group I mGluRs and the second, 2-chloro-5-hydroxyphenylglycine (CHPG), selectively activates subtype 5., The agonists were given by intra-cerebro ventricular injection (ICV) in adult (P60) male Sprague-Dawley rats. The agonists were diluted in saline solution (S) and given at doses of 0.83 [mu]mol/10 [mu]l for DHPG and 3.33 [mu]mol/10 [mu]l for CHPG. Control rats received the same volume of S. To assess neurogenesis, rats of each experimental and control group were given two injections of 5-bromodeoxyuridine (BrdU, 50 mg/kg, intraperitoneal) within a two-hour interval and sacrificed 24 hrs after the second injection. This was done at three time-points after agonist injection (7, 14 and 56 days). Immunohistochemical treatment and cell counting techniques were then performed on the brain tissue., No acute convulsion was observed in the different groups. Animals tolerated well their treatment. BrdU-positive cells were found in the subgranular zone (SGZ) of the dentate gyrus (DG) in all groups including controls. An increase of 64% in BrdU-positive cells was observed 7 days after CHPG injection and of 11% post DHPG compared to control rats. Fourteen days after agonist injection the levels were at 47% and 38% for CHPG and DHPG respectively. At 56 days post-injection these levels were lower than that of the controls with a decrease in BrdU-positive cells of 28% for CHPG and of 64% for DHPG compared to controls., These results show that the activation of group I mGluR plays a role in neurogenesis in the adult rat hippocampus. It seems that group I mGluR subtype 5 might have a more important implication than subtype 1 in the activation of neurogenesis in the adult rat hippocampus. We now need to define their contribution in SE., (Supported by Savoy Fundation.)