Accumulating evidence indicates that the medial prefrontal cortex (mPFC) is a site of myelin and oligodendrocyte abnormalities that contribute to psychotic symptoms of
schizophrenia. The development of therapeutic approaches to enhance remyelination, a regenerative process in which new myelin sheaths are formed on demyelinated axons, may be an attractive remedial strategy.
Geissoschizine methyl
ether (GM) in the Uncaria hook, a galenical constituent of the traditional Japanese medicine
yokukansan (
Yi-gan san), is one of the active components responsible for the psychotropic effects of
yokukansan, though little is known about the mechanisms underlying the effects of either that medicine or GM itself. In the present study, we employed a
cuprizone (CPZ)-induced
demyelination model and examined the cellular changes in response to GM administration during the remyelination phase in the mPFC of adult mice. Using the mitotic marker
5-bromo-2'-deoxyuridine (
BrdU), we demonstrated that CPZ treatment significantly increased the number of
BrdU-positive NG2 cells, as well as microglia and mature oligodendrocytes in the mPFC. Newly formed oligodendrocytes were increased by GM administration after CPZ exposure. In addition, GM attenuated a decrease in
myelin basic protein immunoreactivity caused by CPZ administration. Taken together, our findings suggest that GM administration ameliorated the myelin deficit by mature oligodendrocyte formation and remyelination in the mPFC of CPZ-fed mice. The present findings provide experimental evidence supporting the role for GM and its possible use as a remedy for
schizophrenia symptoms by promoting the differentiation of progenitor cells to and myelination by oligodendrocytes.