Vitamin K enhances the production of brain sulfatides during remyelination

Abstract

Multiple sclerosis (MS) is a devastating neurological disease, which is characterized by mul-tifocal demyelinating lesions in the central nervous system. The most abundant myelin lipids are galactosylceramides and their sulfated form, sulfatides, which together account for about 27% of the total dry weight of myelin. In this study we investigated the role of Vitamin K in remyelination, by using an animal model for MS, the cuprizone model. Demyelination was induced in C57Bl6/J mice, by feeding them a special diet containing 0.3% cuprizone (w/w) for 6 weeks. After 6 weeks, cuprizone was removed from the diet and mice were allowed to remyelinate for either 1 or 3 weeks, in the absence or presence of Vitamin K (i.p. phylloquinone, 2mg, three times per week). Vitamin K enhanced the production of total brain sulfatides, after both 1 week and 3 weeks of remyelination (n = 5, P-values were <0.0001), when compared with the control group. To determine whether or not there is a synergistic effect between vitamins K and D for the production of brain sulfatides, we employed a similar experiment as above. Vitamin K also increased the production of individual brain sulfatides, including d18:1/18:0, d18:1/20:0, d18:1/24:0, and d18:1/24:1 after 3 weeks of remyelination, when compared to the control group. In addition, Vitamin D enhanced the production of total brain sulfatides, as well as d18:1/18:0, d18:1/24:0, and d18:1/24:1 sulfatides after 3 weeks of remyelination, but no synergistic effect between vitamins K and D for the production of total brain sulfatides was observed.