title: Efficacy of vitamin D in treating multiple sclerosis-like neuroinflammation depends on developmental stage.
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.
authors: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: milena.zeitelhofer-adzemovic@ki.se.
authors: Milena Z
authors: MZ
authors: Adzemovic
authors: Manuel
authors: M
authors: Zeitelhofer
authors: Sonja
authors: S
authors: Hochmeister
authors: Sven A
authors: SA
authors: Gustafsson
authors: Maja
authors: M
authors: Jagodic
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D019587:Dietary Supplements; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D014807:Vitamin D
keywords: Developmental stages; EAE; Multiple sclerosis; T cell response; Vitamin D supplementation