Experimental modelsFriday, October 04, 2013, 15:30 - 17:00
High dose vitamin D3 improves remyelination and oligodendrocyte maturation in the cuprizone modelA.E. Nystad, S. Wergeland, L. Aksnes, K.M. Myhr, L. Bø, Ø. Torkildsen (Bergen, NO)
Background: Studies have suggested that vitamin D is not only involved in the pathogenesis of multiple sclerosis (MS), but may also influence disease activity. Several authors have recommended that supplementation of vitamin D should be included in the treatment of the disease. Some studies, however, suggests that high dose vitamin D supplements could have negative effects on the remyelination. By using the cuprizone model for de- and remyelination, we aimed to determine the effects of high dose vitamin D3 on the repair process.
Methods: 48 five week old female C57B1/6 mice were used for this experiment. To induce demyelination 0.2 % cuprizone was added to milled mouse chow. Cuprizone exposure was discontinued after seven weeks. The mice received intra-abdominal injections of 1.25-dihydroxy-vitamin D3 or placebo injections twice a week, from week six and throughout week nine. The animals were sacrificed at four time points, week 6, 7, 8 and 10. The brains were removed and post-fixed in 4% paraformaldehyde. Sections were then stained for myelin (Luxol Fast Blue), oligodendrocytes (NOGO-A), astrocytes (GFAP), microglia (MAC3), T-lymphocytes (CD3) and axonal damage (APP).
Results: After 7 weeks of demyelination, the mice given vitamin D3 had more myelin loss than mice given placebo injections. The remaining myelin in the mice given placebo had, however, an unstructured pattern, typical for damaged myelin. After 3 weeks of remyelination the vitamin D group had more myelin than the placebo group (p=0.001). The vitamin D group had a higher number of mature oligodendrocytes throughout the experiment. Mice that received vitamin D had initially increased astrocytosis (p= 0.043) and microglia activation, compared to the placebo group. However, levels of astrocytosis and microglia activation dropped below the placebo group during the remyelination phase. There were no significant differences in the degree of T-lymphocyte infiltration or axonal damage at any time point.
Discussion and conclusion: High dose vitamin D3 appears to have positive effects on remyelination. It seems that vitamin D stimulates oligodendrocyte maturation and removal of damaged myelin debris, through a stimulating effect on astrocytes and microglia recruitment. In conclusion our results point to a possible new mechanism of action for vitamin D in demyelinating diseases and indicate that high dose vitamin D3 has an essential role in myelin repair.
Nothing to disclose
KM Myhr’s work is supported by KG Jebsen Foundation and The University of Bergen, Bergen Norway