Postsynaptic density protein 95 antisense oligodeoxynucleotides inhibits the activation of MLK3 and JNK3 via the GluR6•PSD-95•MLK3 signaling module after transient cerebral ischemia in rat hippocampus

In this study, we investigated the effect of PSD-95 antisense oligodeoxynucleotides on the phosphorylation of MLK3, JNK3 and interactions of MLK3 and PSD-95 with kainate receptor (GluR6) by immunoprecipitation and immunoblotting. Transient (15 min) brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats. The antisense oligodeoxynucleotides of PSD-95 were administrated to the SD rats once per day for 3 days before ischemia. Our data show that the antisense oligodeoxynucleotides could inhibit phosphorylation of MLK3 and JNK3 and decrease the interactions of MLK3 and PSD-95 with GluR6. These results indicate that PSD-95 plays an important role in the formation of the GluR6(.)PSD-95(.)MLK3 signaling module and MLK3 and JNK3 activation in postischemic rat hippocampus. (C) 2004 Elsevier Ireland Ltd. All rights reserved.