Collapse of extracellular glutamate regulation during epileptogenesis: down-regulation and functional failure of glutamate transporter function in rats with chronic seizures induced by kainic acid

We used northern and western blotting to measure the quantity of glutamate and GABA transporters mRNA and their proteins within the hippocampal tissue of rats with epileptogenesis. Chronic seizures were induced by amygdalar i njection of kainic acid 60 days before death. We found that expression of t he mRNA and protein of the glial glutamate transporters GLAST and GLT-1 wer e down-regulated in the kainic acid-administered group. In contrast, EAAC-1 and GAT-3 mRNA and their proteins were increased, while GAT-1 mRNA and pro tein were not changed. We performed in vivo microdialysis in the freely mov ing state. During the interictal state, the extracellular glutamate concent ration was increased, whereas the GABA level was decreased in the kainic ac id group. Following potassium-induced depolarization, glutamate overflow wa s higher and the recovery time to the basal release was prolonged in the ka inic acid group relative to controls. Our data suggest that epileptogenesis in rats with kainic acid-induced chronic seizures is associated with the c ollapse of extracellular glutamate regulation caused by both molecular down -regulation and functional failure of glutamate transport.