Sublethal oxygen-glucose deprivation alters hippocampal neuronal AMPA receptor expression and vulnerability to kainate-induced death

Howard S. Ying, Jochen H. Weishaupt, Margaret Grabb, Lorella M.T. Canzoniero, Stefano L. Sensi, Christian T. Sheline, Hannah Monyer, Dennis W. Choi

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies have suggested that rats subjected to transient global brain ischemia develop depressed expression of GluR-B in CA1 hippocampal neurons. The present study was performed to determine whether a similar change in AMPA receptor expression could be triggered in vitro by sublethal oxygen-glucose deprivation in rat hippocampal neuronal cultures. mRNA was extracted from individual hippocampal neurons via patch electrodes and amplified by RT-PCR 24-48 hr after sublethal oxygen-glucose deprivation. Compared with controls, insulted neurons expressed increased levels of GluR- D flop. As an indication that this change in receptor expression was functionally significant, insulted cultures exhibited increased AMPA- or kainate-induced 45Ca2+ accumulation sensitive to Joro spider toxin and increased vulnerability to kainate-induced death. These data support the hypothesis that exposure to ischemia may enhance subsequent hippocampal neuronal vulnerability to AMPA receptor-mediated excitotoxicity by modifying the relative expression of AMPA receptor subunits in a manner that promotes Ca2+ permeability.

Original languageEnglish (US)
Pages (from-to)9536-9544
Number of pages9
JournalJournal of Neuroscience
Volume17
Issue number24
DOIs
StatePublished - 1997

Keywords

  • Calcium accumulation
  • GluR-D
  • Glutamate receptor regulation
  • Ischemia
  • Neuronal vulnerability
  • Single cell RT-PCR

ASJC Scopus subject areas

  • Neuroscience(all)

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