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 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) and kainate-type glutam...

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Bibliographic Details
Published in:	Neurobiology of disease Vol. 14; no. 3; pp. 336 - 348
Main Authors:	Leuchtmann, Elizabeth A, Ratner, Andrea E, Vijitruth, Rattanavijit, Qu, Yun, McDonald, John W
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-12-2003 Elsevier
Subjects:	AMPA Animals Apoptosis Apoptosis - drug effects Apoptosis - physiology Astrocytes - drug effects Astrocytes - metabolism Biomarkers Caspases - metabolism Caspases - pharmacology Cell Death - drug effects Cell Death - physiology Cells, Cultured Coculture Techniques Demyelination Drug Resistance - physiology Excitatory Amino Acid Antagonists - pharmacology Excitotoxicity Glutamate Kainate Kainic Acid - pharmacology Mice Murine culture Myelin Necrosis Nerve Fibers, Myelinated - pathology Nerve Growth Factors - metabolism Nerve Growth Factors - pharmacology Neurotoxins - metabolism Oligodendrocyte Oligodendroglia - drug effects Oligodendroglia - metabolism Receptors, AMPA - antagonists & inhibitors Receptors, AMPA - metabolism Receptors, Kainic Acid - antagonists & inhibitors Receptors, Kainic Acid - metabolism AMPA Kainate Oligodendrocyte Demyelination Myelin Excitotoxicity Murine culture Glutamate Necrosis Apoptosis
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0969-9961 1095-953X
DOI:	10.1016/j.nbd.2003.07.004