Abstracts

Kindling is a form of epileptogenesis that can be induced with pentylenetetrazol (PTZ). We undertook this study to evaluate the contribution of glutamate and GABA transporters in the process of PTZ kindling., Rats were kindled with PTZ (40 mg/kg) injected i.p. three times per week until two consecutive stage five seizures were observed.
Experiment 1
Animals underwent pentobarbital anesthesia and decapitation at 24 hours (Group A) or at 30 days (Group B) after their last PTZ induced seizure. Rats in Group A and B were compared with each control rats (Group C and D).
Experiment 2
We collected early-established animals (Group E) and kindling resistant animals (Group F). Early-established rats had consecutive stage five seizures with less than 5 injections of PTZ. Kindling resistant animals did not have fully kindled seizures by 12 injections of PTZ. Under anesthesia with sodium pentobarbital brain tissue was collected at 30 days after the last PTZ injection.
We used western blotting to measure the changes in hippocampal glutamate and GABA transporters in all animals., GLAST, GLT-1 and EAAC-1 of Group A were elevated significantly compared with Group C. No change was found in any transporters of Group B compared with Group D. However, at 30 days (Group B) after their last PTZ induced seizure, animals had stage 5 seizure with PTZ. In early-established rats (Group E), levels of EAAC1 and GAT1 were decreased by 30% when compared to kindling resistant animals (Group F). In these animals, the level of GLT-1, GLAST and GAT3 equaled control., Activation of NMDA receptors is critical to the kindling process. Since all glutamate transporters were increased at 24 hours after establishing kindling with PTZ we considered this effect a response to seizure induced glutamate turnover. While animals remain kindled at the chronic phase, the lack of sustained changes in glutamate transporters suggest these proteins are not involved in the maintenance of epileptogenesis. We wonder if the glutamate and GABA transporters might be operant in the convulsion threshold set factor or as a pace factor for kindling., (Supported by a Grant-in-Aid for Encouragement of Young Scientists (17591223) from the Ministry of Education, Science, Sport and Culture, Japan (to T.D.).)