Seasonal, gestational and postnatal influences on multiple sclerosis: the beneficial role of a vitamin D supplementation during early life.

摘要

There is now strong evidence linking vitamin D, the steroid hormone of sunlight, and Multiple Sclerosis (MS). Two of the most intriguing findings are the season of birth and childhood sun exposure effects. They both suggest that a vitamin D deficiency during these critical imprinting periods is a risk factor for MS. After having confirmed that people born in November are at lower risk of developing MS, we devised a mouse model of prenatal vitamin D deficiency. We observed that adult offspring born to vitamin D deficient mothers, when compared to control offspring, developed a striking milder and delayed experimental autoimmune encephalomyelitis (EAE) and permanently overexpressed the vitamin D receptor. This unexpected finding led us to conjecture that the newborns, after having known an in utero vitamin D-deficient environment, were highly sensitive ex utero to cholecalciferol-containing diet and interpreted the postnatal food as a vitamin D enriched environment. To validate this hypothesis, we devised a mouse model of postnatal vitamin D supplementation. Interestingly, using the same EAE model, we demonstrated that a delayed onset and less severe symptoms were displayed by postnatally vitamin D-supplemented mice. The latter finding is in accordance with previous animal studies demonstrating that a postnatal vitamin D deficiency induced an earlier onset and an increased symptom severity of EAE and epidemiological reports describing the importance of an adequate supply of vitamin D during early life.