Mature myelin basic protein-expressing oligodendrocytes are insensitive to kainate toxicity

Paul A. Rosenberg, Weimin Dai, Xiao Dong Gan, Sanjida Ali, Jennifer Fu, Stephen A. Back, Russell M. Sanchez, Michael M. Segal, Pamela L. Follett, Frances E. Jensen, Joseph J. Volpe

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

We examined the vulnerability to excitotoxicity of rat oligodendrocytes in dissociated cell culture at different developmental stages. Mature oligodendrocytes that express myelin basic protein were resistant to excitotoxic injury produced by kainate, whereas earlier stages in the oligodendrocyte lineage were vulnerable to this insult. To test the hypothesis that the sensitivity of immature oligodendrocytes and the resistance of mature oligodendrocytes to kainate toxicity were due to differences in membrane responsiveness to kainate, we used whole-cell patch-clamp recording. Oligodendrocyte precursors in cultures vulnerable to kainate toxicity responded to 500 μM kainate with large inward currents, whereas mature myelin basic protein-expressing oligodendrocytes in cultures resistant to kainate toxicity showed no clear response to application of this agonist. We assayed expression of glutamate receptor subunits (GluR) -2, -4, -6, -7, and KA2 using immunoblot analysis and found that expression of all of these glutamate receptors was significantly down-regulated in mature oligodendrocytes. These results suggest a striking developmental regulation of glutamate receptors in oligodendrocytes and suggest that the vulnerability of oligodendrocytes to non-N-methyl-D-aspartate receptor-mediated excitotoxicity might be much greater in developing oligodendrocytes than after the completion of myelination.

Original languageEnglish (US)
Pages (from-to)237-245
Number of pages9
JournalJournal of Neuroscience Research
Volume71
Issue number2
DOIs
StatePublished - Jan 15 2003

Keywords

  • Cerebral palsy
  • Excitotoxicity
  • Glutamate
  • Hypoxia
  • Ischemia
  • Periventricular leukomalacia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Rosenberg, P. A., Dai, W., Gan, X. D., Ali, S., Fu, J., Back, S. A., Sanchez, R. M., Segal, M. M., Follett, P. L., Jensen, F. E., & Volpe, J. J. (2003). Mature myelin basic protein-expressing oligodendrocytes are insensitive to kainate toxicity. Journal of Neuroscience Research, 71(2), 237-245. https://doi.org/10.1002/jnr.10472