title: AMPA receptors are the major mediators of excitotoxic death in mature oligodendrocytes.
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 alpha-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.
authors.affiliation: Center for the Study of Nervous System Injury, Washington University School of Medicine, Box 8518, St. Louis, MO 63108, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Leuchtmann
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Ratner
authors.forename: Rattanavijit
authors.initials: R
authors.lastname: Vijitruth
authors.forename: Yun
authors.initials: Y
authors.lastname: Qu
authors.forename: John W
authors.initials: JW
authors.lastname: McDonald
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers; D020169:Caspases / Q000378:metabolism / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004351:Drug Resistance / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D009336:Necrosis; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020169:Caspases; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D009414:Nerve Growth Factors; D009498:Neurotoxins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors