Oligodendrocytes from forebrain are highly vulnerable to AMPA/kainate receptor-mediated excitotoxicity

JW Mcdonald, SP Althomsons, KL Hyrc, DW Choi… - Nature medicine, 1998 - nature.com
JW Mcdonald, SP Althomsons, KL Hyrc, DW Choi, MP Goldberg
Nature medicine, 1998nature.com
Little is known of the molecular mechanisms that trigger oligodendrocyte death and
demyelination in many acute central nervous system insults. Since oligodendrocytes
express functional α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate-
type glutamate receptors, we examined the possibility that oligodendrocyte death can be
mediated by glutamate receptor overactivation. Oligodendrocytes in primary cultures from
mouse forebrain were selectively killed by low concentrations of AM PA, kainate or …
Abstract
Little is known of the molecular mechanisms that trigger oligodendrocyte death and demyelination in many acute central nervous system insults. Since oligodendrocytes express functional α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate-type glutamate receptors, we examined the possibility that oligodendrocyte death can be mediated by glutamate receptor overactivation. Oligodendrocytes in primary cultures from mouse forebrain were selectively killed by low concentrations of AM PA, kainate or glutamate, or by deprivation of oxygen and glucose. This toxicity could be blocked by the AMPA/kainate receptor antagonist 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX). In vivo, differentiated oligodendrocytes in subcortical white matter expressed AMPA receptors and were selectively injured by microstereotaxic injection of AMPA but not NMDA. These data suggest that oligodendrocytes share with neurons a high vulnerability to AMPA/kainate receptor-mediated death, a mechanism that may contribute to white matter injury in CNS disease.
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