AMPA receptors are the major mediators of excitotoxic death in mature oligodendrocytes.
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.
Leuchtmann
Elizabeth A
EA
Center for the Study of Nervous System Injury, Washington University School of Medicine, Box 8518, St. Louis, MO 63108, USA.
Ratner
Andrea E
AE
Vijitruth
Rattanavijit
R
Qu
Yun
Y
McDonald
John W
JW
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
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