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Effect of high‐dose 1.25 dihydroxyvitamin D 3 on remyelination in the cuprizone model
Author(s) -
Nystad Agnes E.,
Wergeland Stig,
Aksnes Lage,
Myhr KjellMorten,
Bø Lars,
Torkildsen Øivind
Publication year - 2014
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12281
Subject(s) - remyelination , calcitriol , medicine , endocrinology , microglia , multiple sclerosis , intraperitoneal injection , placebo , vitamin d and neurology , myelin , immunology , central nervous system , pathology , inflammation , alternative medicine
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 D 3 (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.