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 journalArticlepeer-review

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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