Enhanced remyelination during late pregnancy: involvement of the GABAergic system

Pregnant women with MS experience fewer relapses, especially during the third trimester. In this study, we explore the cellular and molecular events that bring about the protective effect of late pregnancy on the course of de/remyelination in rats. Using cellular, molecular, and ultrastructural methods, we explored remyelination in response to a focal demyelination in the corpus callosum of late pregnant, virgin, and postpartum rats. We further explored the role of GABA(A) receptor (GABA(A)R) in the promyelinating effect observed during late pregnancy. Remyelination in response to a gliotoxin-induced demyelination in the corpus callosum was enhanced in late pregnant rats when compared to that seen in virgin and postpartum rats. This pregnancy-associated promyelinating effect was lost when either the GABA(A)R was blocked or when 5 alpha-reductase, the rate limiting enzyme for the endogenous GABA(A)R activator allopregnanolone, was inhibited. Taken together, these data suggest that the pregnancy-associated pro-myelination operates, at least in part, through a GABAergic activated system.