The link between excitotoxic oligodendroglial death and demyelinating diseases

Trends Neurosci. 2001 Apr;24(4):224-30. doi: 10.1016/s0166-2236(00)01746-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity / drug effects
  • Autoimmunity / physiology*
  • Cell Death / drug effects
  • Cell Death / physiology
  • Demyelinating Diseases / drug therapy
  • Demyelinating Diseases / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Glutamic Acid / metabolism*
  • Humans
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology
  • Neurotoxins / antagonists & inhibitors
  • Neurotoxins / metabolism*
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism*
  • Optic Nerve / drug effects
  • Optic Nerve / pathology
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism
  • Receptors, Kainic Acid / antagonists & inhibitors
  • Receptors, Kainic Acid / metabolism


  • Gluk2 kainate receptor
  • Neurotoxins
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Glutamic Acid