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季节、妊娠和产后对多发性硬化症的影响:在生命早期补充维生素 D 的有益作用。

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

机构信息

Aix-Marseille Univ, NICN, CNRS UMR 6184, 13015 Marseille, France.

出版信息

J Neurol Sci. 2011 Dec 15;311(1-2):64-8. doi: 10.1016/j.jns.2011.08.044. Epub 2011 Sep 17.

DOI:10.1016/j.jns.2011.08.044
PMID:21930286
Abstract

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.

摘要

现在有强有力的证据将维生素 D(阳光中的类固醇激素)与多发性硬化症(MS)联系起来。最引人注目的两个发现是出生季节和儿童期阳光暴露的影响。它们都表明,在这些关键的“印记”时期缺乏维生素 D 是 MS 的一个风险因素。在证实 11 月出生的人患 MS 的风险较低之后,我们设计了一种产前维生素 D 缺乏症的小鼠模型。我们观察到,与对照组后代相比,维生素 D 缺乏症母亲所生的成年后代会发展出一种明显较轻和延迟的实验性自身免疫性脑脊髓炎(EAE),并且永久性地过度表达维生素 D 受体。这一意外发现使我们推测,新生儿在经历了宫内维生素 D 缺乏环境后,对外源性胆钙化醇(维生素 D 的一种形式)饮食高度敏感,并将产后食物解释为富含维生素 D 的环境。为了验证这一假设,我们设计了一种产后维生素 D 补充的小鼠模型。有趣的是,使用相同的 EAE 模型,我们证明了产后补充维生素 D 的小鼠表现出发病延迟和症状较轻。后一种发现与先前的动物研究一致,这些研究表明,产后维生素 D 缺乏会导致 EAE 的发病更早且症状更严重,以及描述生命早期充足供应维生素 D 的重要性的流行病学报告。

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