AMPA receptors are the major mediators of excitotoxic death in mature oligodendrocytes |
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Authors: | Leuchtmann Elizabeth A Ratner Andrea E Vijitruth Rattanavijit Qu Yun McDonald John W |
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Institution: | Center for the Study of Nervous System Injury, Washington University School of Medicine, Box 8518, St. Louis, MO 63108, USA. |
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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. |
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Keywords: | AMPA Demyelination Excitotoxicity Glutamate Kainate Myelin Murine culture Oligodendrocyte Necrosis Apoptosis |
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