Abbreviated exposure to cuprizone is sufficient to induce demyelination and oligodendrocyte loss (2013)

Undergraduates: Vivian Doan, Dr. Lorelei Taylor

Faculty Advisor: Glenn Matsushima
Department: Biology

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Cuprizone intoxication is one of several animal models used to study demyelination and remyelination. Early treatment protocols exposed mice to cuprizone for six weeks to induce demyelination; however more recent reports have varied exposure times from four to five weeks. The goal of this study was to determine the minimal exposure of cuprizone in C57BL/6 mice that would induce a pathology of robust demyelination and gliosis similar to that described for a five or six week treatment. We found that an abbreviated insult of only three weeks exposure to cuprizone produced extensive demyelination two weeks later (five-week time point), equivalent to that observed with five weeks exposure. The depletion of mature oligodendrocytes, as well as microglia and astrocyte accumulation, showed trends similar to five-week exposure to cuprizone. Once mature oligodendrocytes are perturbed after a three-week treatment period, the progression to demyelination occurs without requiring further exposure. Furthermore, the early removal of cuprizone did not accelerate remyelination suggesting other sequences of events must follow before repair can occur. Thus, a short ¿hit and run¿ CNS insult triggers a cascade of events leading to complete demyelination two weeks later.