In order to investigate the molecular mechanism underlying high seizure susceptibility of GLAST knockout mice, we carried out Western blotting for the expression of GLT-1, EAAC-1, and several kinds of glutamate receptors in the hippocampus and the cortex. Although no significant difference was observed between GLAST (+/+) and (-/-) mice in terms of expression of GLT-1 and EAAC-1 in the hippocampus, these proteins were over-expressed in the frontal cortex in GLAST (-/-) mice (GLT-1, about 210% increase; EAAC-1, about 180% increase). Expression of hippocampal Glu-R1 and Glu-R2 in GLAST (-/-) mice was remarkably increased (Glu-R1, about 140% increase; Glu-R2, about 160% increase), while Glu-R3 and NMDA receptors levels (NMDA-R1, 2A and 2B) were equal to those in control. Cortical levels of Glu-R1, -R2 and -R3 receptors in GLAST (-/-) mice were remarkably decreased (Glu-R1, about 60% decrease; Glu-R2, about 60% decrease; Glu-R3, about 70% decrease), while NMDA receptors were remarkably increased in comparison to those in GLAST (+/+) mice (N-R1, about 150% increase; N-R2A, about 150% increase; N-R2B, about 140% increase). These data suggest that the increased susceptibility to seizures in GLAST (-/-) mice might be derived from increased expression of Glu-R1 in the hippocampus coupled with decreased cortical expression of Glu-R2 and increased NMDA-R1 and -2A, -2B expression.
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