title: Effect of high-dose 1.25 dihydroxyvitamin D3 on remyelination in the cuprizone model.
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.
authors.affiliation: Department of Neurology, Norwegian Multiple Sclerosis Competence Centre, Haukeland University Hospital, Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Agnes E
authors.initials: AE
authors.lastname: Nystad
authors.forename: Stig
authors.initials: S
authors.lastname: Wergeland
authors.forename: Lage
authors.initials: L
authors.lastname: Aksnes
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.forename: Lars
authors.initials: L
authors.lastname: Bø
authors.forename: Oivind
authors.initials: O
authors.lastname: Torkildsen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage*; D003471:Cuprizone / Q000008:administration & dosage / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D000070798:Nogo Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse; D003471:Cuprizone; D002117:Calcitriol
keywords: Multiple sclerosis; calcitriol; cuprizone; remyelination; vitamin D