Abstracts

RATIONALE: GLAST knockout mice have severe seizures induced by kindling or by pentylenetetrazole, an effect possibly related to intensely enhanced glutamatergic excitatory synaptic transmission. These changes may be related to altered expression of glutamate receptors METHODS: We performed western blots to measure alterations in glutamate receptors both in the hippocampus and frontal cortex of GLAST knockout mice; wild type mice (C57BL-6J) were controls. RESULTS: Expression of hippocampal non-NMDA receptors (Glu-R1, Glu-R2 & 3) in GLAST (-/-) mice was increased, while NMDA receptors (NMDA-R1, R2A & R2B) levels were equal to control. Cortical levels of the non-NMDA receptors were decreased, while NMDA receptors were increased when compared to that of the wild type. CONCLUSIONS: In general, increased expression of Glu-R2 suppresses glutamate receptor-mediated Ca++ influx. With decreased NMDA-R1 & 2A,2B, increased Glu-R2 expression would have a compensatory role to limit excitotoxicity induced by glutamate receptor mediated Ca++ influx in the hippocampus. Expression of NMDA-R1 & 2A,2B in the hippocampus equal to the wild type supports the observation that amygdaloid kindling is not more rapid than controls. We suggest that increased severity of seizures in GLAST knockout mice might be derived from increased expression of Glu-R1 in the hippocampus coupled with decreased cortical expresson of Glu-R2 and increased NMDA-R1 & 2A,2b expression.