title: Geissoschizine methyl ether, an alkaloid from the Uncaria hook, improves remyelination after cuprizone-induced demyelination in medial prefrontal cortex of adult mice.
abstract: 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.
authors.affiliation: Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan, morita@naramed-u.ac.jp.
authors.forename: Shoko
authors.initials: S
authors.lastname: Morita
authors.forename: Kouko
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Manabu
authors.initials: M
authors.lastname: Makinodan
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okuda
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Akio
authors.initials: A
authors.lastname: Wanaka
mesh_terms: D000818:Animals; D003471:Cuprizone / Q000494:pharmacology*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy; D026121:Indole Alkaloids; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D004676:Myelin Basic Protein / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects
chemical_list: D026121:Indole Alkaloids; D007211:Indoles; D004676:Myelin Basic Protein; C110832:geissoschizine methylether; D003471:Cuprizone