AMPA receptors are the major mediators of excitotoxic death in mature oligodendrocytes

Elizabeth A. Leuchtmann, Andrea E. Ratner, Rattanavijit Vijitruth, Yun Qu, John W. McDonald

Research output: Contribution to journalArticle

Abstract

Myelination of axons is important for central nervous system function, but oligodendrocytes, which constitute CNS myelin, are vulnerable to excitotoxic injury and death. Although mature oligodendrocytes express functional α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) and kainate-type glutamate receptors, the relative roles of these subtypes in excitotoxicity are not well understood. Using recently developed selective antagonists for subtypes of ionotropic non-NMDA receptors, we addressed this issue. By examining the pharmacological, biochemical, and morphologic features of kainite-induced excitotoxic death, we also determined whether it occurs by apoptosis, necrosis, or both. We conclude that when mature oligodendrocytes die after exposure to kainate: (1) AMPA receptors are the most important mediators, (2) kainate receptors play a smaller role, and (3) death occurs predominantly by necrosis, not apoptosis.

Original languageEnglish (US)
Pages (from-to)336-348
Number of pages13
JournalNeurobiology of Disease
Volume14
Issue number3
DOIs
StatePublished - Dec 2003

Keywords

  • AMPA
  • Apoptosis
  • Demyelination
  • Excitotoxicity
  • Glutamate
  • Kainate
  • Murine culture
  • Myelin
  • Necrosis
  • Oligodendrocyte

ASJC Scopus subject areas

  • Neurology

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  • Cite this

    Leuchtmann, E. A., Ratner, A. E., Vijitruth, R., Qu, Y., & McDonald, J. W. (2003). AMPA receptors are the major mediators of excitotoxic death in mature oligodendrocytes. Neurobiology of Disease, 14(3), 336-348. https://doi.org/10.1016/j.nbd.2003.07.004