OLIGODENDROCYTES FROM FOREBRAIN ARE HIGHLY VULNERABLE TO AMPA KAINATERECEPTOR-MEDIATED EXCITOTOXICITY/

Little is known of the molecular mechanisms that trigger oligodendrocy te death and demyelination in many acute central nervous system insult s. Since oligodendrocytes express functional lpha-amino-3-hydroxy-5-me thyl-4-isoxazolepropionic acid (AMPA)/kainate-type glutamate receptors , we examined the possibility that oligodendrocyte death can be mediat ed by glutamate receptor overactivation. Oligodendrocytes in primary c ultures from mouse forebrain were selectively killed by low concentrat ions of AMPA, kainate or glutamate, or by deprivation of oxygen and gl ucose. This toxicity could be blocked by the AMPA/kainate receptor ant agonist 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX).,ln vi vo, differentiated oligodendrocytes in subcortical white matter expres sed AMPA receptors and were selectively injured by microstereotaxic in jection of AMPA but not NMDA. These data suggest that oligodendrocytes share with neurons a high vulnerability to AMPA/kainate receptor-medi ated death, a mechanism that may contribute to white matter injury in CNS disease.