Elsevier

Brain Research

Volume 659, Issues 1–2, 3 October 1994, Pages 67-74
Brain Research

Glutamate-induced overexpression of NMDA receptor messenger RNAs and protein triggered by activation of AMPA/kainate receptors in rat hippocampus following forebrain ischemia

https://doi.org/10.1016/0006-8993(94)90864-8Get rights and content

Abstract

Severe forebrain ischemia induces a large increase in expression of NMDA receptor subunits in rat brain. One week after ischemia, levels of NMDA-R1 mRNAs in the CA1 pyramidal cells of hippocampus are 7 times higher than those observed in control rats. At 7 days postischemia, an enhanced immunostaining of the NMDA-R1 subunit was observed in all hippocampal structures indicating that changes in mRNA levels are accompanied by changes in receptor protein level. Riluzole, a potent inhibitor of glutamate release and CNQX, a selective AMPA/kainate antagonist, drastically reduced the ischemia-induced expression of mRNAs for three NMDA receptor subunits while d-AP5, a selective NMDA antagonist, had essentially no effect. Therefore ischemia-induced expression of NMDA receptor subunits is associated with glutamate release and proceeds via an AMPA/kainate pathway. These results together with those of other groups concerning ischemia effects on AMPA and GABA A receptor levels, suggest an important role of the induced expression of NMDA receptor subunits in the deleterious effects of ischemia.

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