Long-term increase of GluR2 α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunit in the dispersed dentate gyrus after intrahippocampal kainate injection in the mouse

Abstract

Intrahippocampal injection of a subtoxic dose of kainate in mice has been shown to induce a dispersion of granule cells of the dentate gyrus, which is a characteristic morphological change often seen in human hippocampal sclerosis. In addition, it has been shown recently that such injections lead to recurrent hippocampal seizures and changes in glucose metabolism, which are reminiscent of temporal lobe epilepsy. Previous reports on human hippocampal sclerosis have shown an increase of the expression of the GluR2 α-amino-3-hydroxy-5-methylisoxazole-4-propionate subunits in the dispersed granule cell somata. However, no such changes have been observed so far in animal models of epilepsy with hippocampal sclerosis. In this study, the expression of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunits was examined by immunohistochemistry following intrahippocampal injection of kainate in mice and rats. In mice, such injection induced a persistent increase of GluR2 immunoreactivity in the granule cells for up to 180 days. By contrast, GluR1 immunoreactivity was transiently increased during the first four days after the injection and progressively decreased thereafter. By contrast, intrahippocampal injection of kainate in rats did not result in granule cell dispersion and no changes in GluR1 immunoreactivity or GluR2 immunoreactivity were observed. These results show that, in addition to morphological, clinical and metabolical similarities, intrahippocampal injection of kainate results in a persistent increase of GluR2 associated with granule cell dispersion, as in human hippocampal sclerosis. These data suggest the existence of common mechanisms between granule cell dispersion and regulation of GluR2 subunits associated with hippocampal sclerosis.