Journal of Multiple Sclerosis

Nobiletin Induces Oligodendrocyte Lineage Precursor Cells in a Cuprizone-Administered Demyelination Animal Model

Mitsunari Nakajima, Risei Shimizu, Kohei Furuta, Mami Sugino, Takashi Watanabe, Rui Aoki, Satoshi Okuyama and Yoshiko Furukawa

We investigated the effect of nobiletin on the oligodendroglial cell lineage in a cuprizone-induced demyelination animal model. Nobiletin, a polymethoxyflavone, was administered to the model animal for 3 consecutive weeks (50 mg/kg, intraperitoneally, 2 times/week). Immunohistochemical analysis of the corpus callosum and/or Western blotting analysis of brain extracts revealed that cuprizone administration reduced immunoreactivity for myelin-basic protein (MBP), a marker for mature oligodendrocytes, and increased immunoreactivity for platelet derived-growth factor receptor (PDGFR)-α, a marker for oligodendrocyte precursor cells (OPCs). Nobiletin treatment did not affect these changes in the cuprizone-fed mice. Nobiletin treatment, however, increased the immunoreactivity against proteolipid protein (PLP)/DM-20, a marker for mature oligodendrocytes, OPCs, and oligodendrocyte lineage precursor cells, and also augmented immunoreactivity against oligodendrocyte transcription factor 2 (olig2), a marker for OPCs and their precursor cells. These findings suggest that nobiletin promotes the production of oligodendrocyte lineage precursor cells in a demyelination animal model, and that nobiletin treatment might be suitable for individuals with demyelination diseases such as multiple sclerosis.