Slowing down demyelination: the effect of a nerve growth factor mimetic on oligodendrocyte death (2009)

Undergraduate: Jason Phillippi

Faculty Advisor: Glenn Matsushima
Department: Chemistry

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Demyelination and associated oligodendrocyte apoptosis in the brain play an important role in pathologies such as multiple sclerosis. ProNGF is known to bind p75NTR receptors and to induce cell death of mature oligodendrocytes in culture. The cuprizone-induced demyelination features apoptotic oligodendrocytes and it is a model that provides a convenient method of analyzing the processes of demyelination and remyelination over a highly reproducible time course. In this study, we examine whether a novel small nonpeptidyl proNGF mimetic, C31, abrogates apoptosis of oligodendrocytes in mice exposed to cuprizone intoxication. At three and five weeks of cuprizone treatment, cellular profiles in the corpus callosum were analyzed using immunohistochemical methods. At three weeks, mice treated with C31 were found to have significantly greater numbers of mature oligodendrocyte than mice without C31. C31 appeared to specificially affect oligodendrocytes as other cell populations were unaffected. Increased survival of oligodendrocytes was not found at five weeks of cuprizone treatment. Thus, C31 appeared to have a protective effect; however, this was temporary and limited. These studies are encouraging and additional testing of C31 are ongoing to determine whether it could provide therapeutic benefits in demyelinating diseases.