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 kai nate 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 the ir own transporters. However, acute and chronic alterations in glutamate ho meostasis can result in overactivation of AM PA and kainate receptors and s ubsequent excitotoxic oligodendroglial death. Furthermore, demyelinating le sions caused by excitotoxins can be similar to those observed in multiple s clerosis. This, together with the effect of AMPA and kainate receptor antag onists in ameliorating the neurological score of animals with experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis), indic ates that oligodendrocyte excitotoxicity could be involved in the pathogene sis of demyelinating disorders.