Oligodendrocytes are highly susceptible to oxidative stress that is the primary feature of the most common pathological conditions affecting the CNS, such as stroke, spinal cord and head injuries, Multiple Sclerosis, and possibly abnormalities associated with aging, e.g. Alzheimer disease. The experimental strategy of this research is to delineate molecular pathways activated by oxidative stress that initially impair the ability of oligodendrocytes to maintain the myelin sheaths, and ultimately lead to cell death. The aim is to gain control of these pathways through the modulation of gene expression by antisense technology, as well as through the administration of assorted antioxidants and other pharmaceuticals. This, in turn, will provide a foundation for the development of medical strategies that would prevent or diminish white matter destruction following pathological incidents, and hence, minimize neurological deficits. Structural characterization of myelin-associated glycoprotein gene core promoter .
Selenium is required for normal upregulation of myelin genes in differentiating oligodendrocytes.
Vulnerability of oligodendrocytes to anoxia. Delayed oligodendrocyte degeneration induced by brief exposure to hydrogen peroxide. Chromatin fragmentation in oxidatively stressed oligodendrocytes. Oxidative stress induces delayed degeneration of oligodendrocytes. Implications for inflammatory demyelination.