期刊
EXPERIMENTAL NEUROLOGY
卷 249, 期 -, 页码 39-48出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2013.08.002
关键词
Vitamin D supplementation; Developmental stages; EAE; Multiple sclerosis; T cell response
资金
- Biogens Idec
- Wenner-Gren Foundation
- Swedish Research Council
- Swedish Brain Foundation
- Swedish Association of Persons with Neurological Disabilities
- Harald and Greta Jeanssons Foundation
- Ake Wibergs Foundation
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-gamma 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. (C) 2013 The Authors. Published by Elsevier Inc All rights reserved.
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