NMDA and non-NMDA receptor gene expression following global brain ischemia in rats: effect of NMDA and non-NMDA receptor antagonists.
Transient forebrain or global ischemia in rats induces selective and delayed damage of hippocampal CA1 neurons. In a previous study, we have shown that expression of GluR2, the kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit that governs Ca2+ permeability, is preferentially reduced in CA1 at a time point preceding neuronal degeneration. Postischemic administration of the selective AMPA receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), protects CA1 neurons against delayed death. In this study we examined the effects of NBQX (at a neuroprotective dose) and of MK-801 (a selective NMDA receptor antagonist, not protective in this model) on kainate/AMPA receptor gene expression changes after global ischemia. We also examined the effects of transient forebrain ischemia on expression of the NMDA receptor subunit NMDAR1. In ischemic rats treated with saline, GluR2 and GluR3 mRNAs were markedly reduced in CA1 but were unchanged in CA3 or dentate gyrus. GluR1 and NMDAR1 mRNAs were not significantly changed in any region examined. Administration of NBQX or MK-801 did not alter the ischemia-induced changes in kainate/AMPA receptor gene expression. These findings suggest that NBQX affords neuroprotection by a direct blockade of kainate/AMPA receptors, rather than by a modification of GluR2 expression changes.
Pellegrini-Giampietro
D E
DE
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York.
Pulsinelli
W A
WA
Zukin
R S
RS
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D017403:In Situ Hybridization; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000235:genetics*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015424:Reperfusion
D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline