Steven M. LeVine, Ph.D.

Multiple sclerosis is a neurological disorder that can lead to sensory and motor deficits. Autoimmune reactions against myelin antigens are thought to induce oxidative stress. The oligodendrocyte produces myelin and it is thought to be particularly vulnerable to oxidative stress since it has a high concentration of iron together with a high concentration of lipids, which are prone to lipid peroxidation. We hypothesize that the oligodendrocyte has specialized defense mechanisms designed to counter oxidative stress. Furthermore, we suggest that during multiple slcoersis there is an ongoing battle between inflammatory mediators that target oligodendrocytes/myelin and the defense mechanisms that counter this stress, and the balance between pathogenic and protective forces determines whether oligodendrocytes die or survive. We are utilizing the animal model of multiple sclerosis called experimental autoimmune encephalomyelitis to investigate the endogenous protective mechanisms within oligodendrocytes. In addition to multiple sclerosis, we are investigating a second demyelinating called globoid cell leukodystrophy (a.k.a., Krabbe disease) and the pathogenic reactions of various toxins.

(Left) Iron catalyzes the formation of free radicals [dot on L (lipid) or O (oxygen)] which are reactive and can lead to lipid peroxidation. Molecules surrounded by circles promote oxidative stress and have a pro-pathogenic role. Molecules surrounded by rectangles are inert. Glutathione peroxidase converts reduced glutathione (GSH) and hydrogen peroxide (H2O2) into oxidized glutathione (GSSG) and water, while glutathione peroxidase and glutathione S-transferase convert GSH and lipid hydroperoxide (LO2H) into GSSH, water and lipid alcohol (LOH).

(Above) Iron histochemistry reveals an abundance of staining in both oligodendrocytes and myelin.