Abstracts

RATIONALE:We measured mRNA (northern blot) and glutamate transporters (western blot) GLAST, GLT-1, EAAC-1 and the ?-aminobutyric acid (GABA) transporters GAT-1 and GAT-3 within hippocampal tissue of rats. METHODS: Animals used had amygdalar kainic acid injection 60 days before and had chronic recurrent seizures. Functional consequences of molecular changes were measured with in vivo microdialysis in freely moving animals challenged with potassium-induced depolarization. RESULTS: Glial glutamate transporters GLAST and GLT-1 were down regulated. In contrast, mRNA and proteins for EAAC-1 and GAT-3 were increased, while GAT-1 mRNA and proteins were not changed. During the interictal state, extracellular glutamate concentration was increased, while GABA levels were decreased. Depolarization induced by potassium infusion through the dialysis probe caused the glutamate-GABA ratio to increase and recovery time to basal glutamate levels to be delayed. Redox state favoring oxidation was corroborated by demonstration of impaired free radical scavenging potential in hippocampal regions giving rise to chronic behavioral seizures. CONCLUSIONS: Our data suggest that chronic epileptogenesis in rats with chronic seizures induced by kainic acid is related to collapse of extracellular glutamate regulation caused by both the molecular down-regulation and the functional failure of the transport of glutamate.