Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats.
Severe, transient global ischemia of the brain induces delayed damage to specific neuronal populations. Sustained Ca2+ influx through glutamate receptor channels is thought to play a critical role in postischemic cell death. Although most kainate-type glutamate receptors are Ca(2+)-impermeable, Ca(2+)-permeable kainate receptors have been reported in specific kinds of neurons and glia. Recombinant receptors assembled from GluR1 and/or GluR3 subunits in exogenous expression systems are permeable to Ca2+; heteromeric channels containing GluR2 subunits are Ca(2+)-impermeable. Thus, altered expression of GluR2 in development or following a neurological insult or injury to the brain can act as a switch to modify Ca2+ permeability. To investigate the molecular mechanism underlying delayed postischemic cell death, GluR1, GluR2, and GluR3 gene expression was examined by in situ hybridization in postischemic rats. Following severe, transient forebrain ischemia GluR2 gene expression was preferentially reduced in CA1 hippocampal neurons at a time point that preceded their degeneration. The switch in expression of kainate/AMPA receptor subunits coincided with the previously reported increase in Ca2+ influx into CA1 cells. Timing of the switch indicates that it may play a causal role in postischemic cell death.
Pellegrini-Giampietro
D E
DE
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
Zukin
R S
RS
Bennett
M V
MV
Cho
S
S
Pulsinelli
W A
WA
D000704:Analysis of Variance; D000818:Animals; D016375:Antisense Elements (Genetics); D001345:Autoradiography; D015870:Gene Expression; D006624:Hippocampus / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D007700:Kinetics; D046911:Macromolecular Substances; D008297:Male; D011712:Pyramidal Tracts / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000096:biosynthesis / Q000235:genetics*; D013462:Sulfur Radioisotopes; D013997:Time Factors
D016375:Antisense Elements (Genetics); D046911:Macromolecular Substances; D015347:RNA Probes; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D013462:Sulfur Radioisotopes