Effect of high-dose 1.25 dihydroxyvitamin D3 on remyelination in the cuprizone model

APMIS. 2014 Dec;122(12):1178-86. doi: 10.1111/apm.12281. Epub 2014 May 26.

Abstract

Vitamin D supplementation is increasingly recommended to patients with multiple sclerosis (MS). To study the effect of high-dose vitamin D on remyelination, female C57Bl/6 mice were demyelinated with dietary 0.2% cuprizone for 7 weeks. The mice received intraperitoneal injections of 1.25-dihydroxyvitamin D3 (calcitriol) or placebo (vehicle) injections twice a week, from week 6, throughout week 9. Mice that received calcitriol had initially increased demyelination (p = 0.021), astrocytosis (p = 0.043), and microglia activation. However, levels of astrocytosis and microglia activation dropped below those of the placebo group during the remyelination phase. There was a significant increase in myelination in the calcitriol group throughout the remyelination phase (p = 0.041), while the remyelination in the placebo group was not significant (p = 0.317). After 3 weeks of remyelination, the calcitriol group had more myelin than the placebo group (p = 0.001). The calcitriol group had a higher density of NOGO-A positive cells throughout the remyelination phase, and the number of NOGO-A positive cells was significantly higher in the calcitriol group at one week of remyelination (p = 0.019). There were no significant differences in extent of T-lymphocyte infiltration. High-dose calcitriol seems to be safe regarding remyelination. Our results indicate that this treatment could actually promote the repair process, possibly through a stimulating effect on oligodendrocyte maturation and astrocyte activation. The potential of calcitriol to stimulate the remyelination process should be investigated further in functional studies.

Keywords: Multiple sclerosis; calcitriol; cuprizone; remyelination; vitamin D.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Calcitriol / administration & dosage*
  • Cuprizone / administration & dosage
  • Cuprizone / toxicity*
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / pathology*
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Female
  • Gliosis / chemically induced
  • Gliosis / pathology
  • Mice
  • Mice, Inbred C57BL
  • Myelin Proteins / metabolism
  • Myelin Sheath / metabolism
  • Nogo Proteins
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism

Substances

  • Myelin Proteins
  • Nogo Proteins
  • Rtn4 protein, mouse
  • Cuprizone
  • Calcitriol