ALTERATIONS IN GLUTAMATE TRANSPORTER PROTEIN-LEVELS IN KINDLING-INDUCED EPILEPSY

There is increasing evidence that levels of glutamate are elevated in certain brain regions immediately prior to and during induction and pr opagation of seizures. Modulation of high-affinity glutamate uptake is a potential mechanism responsible for the elevated levels observed wi th seizures. To date, three distinct Na+-dependent glutamate transport ers have been cloned from rat and rabbit: GLT-1, GLAST, and EAAC-1. We performed a series of experiments to determine whether levels of thes e transporters are altered in amygdala-kindled rats. Levels of GLT-1, GLAST, and EAAC-1 were examined in three brain regions (hippocampus, p iriform cortex/amygdala, and limbic forebrain) by quantitative immunob lotting using subtype-specific antibodies. GLAST protein was down-regu lated in the piriform cortex/amygdala region of kindled rats as early as 24 h after one stage 3 seizure and persisting through multiple stag e 5 seizures. In contrast, kindling induced an increase in EAAC-1 leve ls in piriform cortex/amygdala and hippocampus once the animals had re ached the stage 5 level. No changes in GLT-1 were observed in any regi on examined. Changes in transporter levels could contribute to the cha nges in glutamate levels seen with kindling.