Efficacy of vitamin D in treating multiple sclerosis-like neuroinflammation depends on developmental stage

Exp Neurol. 2013 Nov;249:39-48. doi: 10.1016/j.expneurol.2013.08.002. Epub 2013 Aug 13.

Abstract

The association of vitamin D deficiency with higher prevalence, relapse rate and progression of multiple sclerosis (MS) has stimulated great interest in using vitamin D supplementation as a preventative measure and even a therapy for established MS. However, there is a considerable lack of evidence when it comes to an age/developmental stage-dependent efficacy of vitamin D action and a time-window for the most effective prophylactic treatment remains unclear. We studied the effect of vitamin D supplementation in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS, at three different developmental stages in rats. Supplementation treatment was initiated: i) prior to gestation and maintained throughout pre- and early postnatal development (gestation and lactation); ii) after weaning, throughout juvenile/adolescence period and iii) in adult age. We observed a marked attenuation of EAE in juvenile/adolescent rats reflected in a less severe CNS inflammation and demyelination, accompanied by a lower amount of IFN-γ producing MOG-specific T cells. Moreover, the cytokine expression pattern in these rats reflected a more anti-inflammatory phenotype of their peripheral immune response. However, the same supplementation regimen failed to improve the disease outcome both in adult rats and in rats treated during pre- and early post-natal development. Our data demonstrate a developmental stage-dependent efficiency of vitamin D to ameliorate neuroinflammation, suggesting that childhood and adolescence should be the target for the most effective preventive treatment.

Keywords: Developmental stages; EAE; Multiple sclerosis; T cell response; Vitamin D supplementation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Dietary Supplements
  • Disease Progression*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Female
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / physiopathology
  • Rats
  • Treatment Outcome
  • Vitamin D / administration & dosage*

Substances

  • Vitamin D