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Brain Advance Access published online on October 27, 2004
Brain, doi:10.1093/brain/awh302
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Received February 22, 2004
Revised July 28, 2004
Accepted July 30, 2004

Article

Resistance of human adult oligodendrocytes to AMPA/kainate receptor-mediated glutamate injury

Karolina Wosik 1, Francesca Ruffini 1, Guillermina Almazan 2, André Olivier 3, Josephine Nalbantoglu 1, and Jack P. Antel 1*

1 Neuroimmunology Unit, Montreal Neurological Institute, Montreal, Quebec, Canada
2 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
3 Department of Neurosurgery, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada

* To whom correspondence should be addressed.
Jack P. Antel, E-mail: jack.antel{at}mcgill.ca


  Abstract

Summary Multiple sclerosis is an inflammatory disease of the CNS leading to the destruction of oligodendrocytes (OLs), myelin sheaths and axons. The mediators of tissue injury remain unknown. Glutamate, which can be released by activated immune cells or produced within the CNS, has been implicated as a potential mediator of tissue injury in multiple sclerosis. {alpha}-Amino-3-hydroxy-5-methyl-4- isoxazole proprionic acid (AMPA) and kainate are highly toxic when added to rodent OL cultures. Using OLs derived from human adult surgical specimens, we investigated AMPA/kainate receptor expression and the effects of receptor stimulation on the viability of human OLs. We find that human adult OLs in vitro express low levels of ionotropic glutamate receptors and are resistant to excitotoxicity mediated by high and sustained doses of AMPA or kainate, even when receptor desensitization is blocked. In contrast, rat OLs show strong AMPA receptor expression and are susceptible to excitotoxicity, as previously demonstrated. Furthermore, we show in human brain sections that OLs do not express AMPA receptors in situ and that glial expression of AMPA receptors is limited to astrocytes. The apparent lack of glutamate receptor expression on human OLs and their resistance to AMPA/kainate toxicity should be considered when postulating mechanisms of tissue injury in multiple sclerosis.

Keywords: glia; multiple sclerosis; astrocytes; oligodendroglia.
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