The link between excitotoxic oligodendroglial death and demyelinating diseases.
Oligodendrocytes, the myelinating cells of CNS axons, are highly vulnerable to excitotoxic signals mediated by glutamate receptors of the AMPA and kainate classes. Receptors in these cells are commonly activated by glutamate that is released from axons and glial cells. In addition, oligodendrocytes contribute to the control of extracellular glutamate levels by means of their own transporters. However, acute and chronic alterations in glutamate homeostasis can result in overactivation of AMPA and kainate receptors and subsequent excitotoxic oligodendroglial death. Furthermore, demyelinating lesions caused by excitotoxins can be similar to those observed in multiple sclerosis. This, together with the effect of AMPA and kainate receptor antagonists in ameliorating the neurological score of animals with experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis), indicates that oligodendrocyte excitotoxicity could be involved in the pathogenesis of demyelinating disorders.
Departamento de Neurociencias, Universidad del País Vasco, 48940 Leioa, Spain. onpmaalc@lg.ehu.es
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Matute
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Alberdi
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Domercq
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Pérez-Cerdá
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Pérez-Samartín
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Sánchez-Gómez
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000097806:GluK2 Kainate Receptor
D018698:Glutamic Acid; D009498:Neurotoxins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor