Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats

Domenico E. Pellegrini-Giampietro, R. Suzanne Zukin, Michael V. L. Bennett, Sunghee Cho, William A. Pulsinelli

Research output: Contribution to journalArticle

341 Citations (Scopus)

Abstract

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 Ca2+-impermeable, Ca2+-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 Ca2+-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/AMP A 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.

Original languageEnglish (US)
Pages (from-to)10499-10503
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number21
StatePublished - 1992

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Glutamate Receptors
Kainic Acid Receptors
Hippocampus
Cell Death
Ischemia
Gene Expression
Neurons
Kainic Acid
Adenosine Monophosphate
Prosencephalon
Brain Ischemia
Neuroglia
Brain Injuries
In Situ Hybridization
Permeability
Population

Keywords

  • α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
  • Excitotoxicity
  • Kainate

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats. / Pellegrini-Giampietro, Domenico E.; Zukin, R. Suzanne; Bennett, Michael V. L.; Cho, Sunghee; Pulsinelli, William A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 21, 1992, p. 10499-10503.

Research output: Contribution to journalArticle

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