Proteomics Unit at University of Bergen (PROBE), Department of Biomedicine, University of Bergen, Norway; Kristian Gerhard Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Neurochem Int. 2018 Jan;112:267-277. doi: 10.1016/j.neuint.2017.08.008. Epub 2017 Aug 14.
Dietary supplementation of vitamin D is commonly recommended to patients with multiple sclerosis. We recently found that high-dose of the hormonally active 1,25-dihydroxyvitamin-D (1,25D) promotes myelin repair in the cuprizone model for de- and remyelination. In the present study, we quantified 5062 proteins, of which 125 were differentially regulated in brain tissue from 1,25D treated mice during remyelination, compared to placebo. Proteins upregulated in the early remyelination phase were involved in calcium binding, e.g. calretinin (>1.3 fold, p < 0.005), S10A5 and secretagogin, and involved in mitochondrial function, e.g. NADH-ubiquinone oxidoreductase chain 3, and acyl-coenzyme A synthetase. Calretinin, S10A5 and secretagogin expression levels were characterized using immunohistochemistry. Calretinin immunoreactivity was significantly increased (>3 fold, p = 0.016) in the medial septal nuclei of 1,25D treated mice in the early remyelination phase. Our results indicate that vitamin D may influence remyelination by mechanisms involving an increase in calretinin expression and potentially other calcium binding proteins.
膳食补充维生素 D 通常被推荐给多发性硬化症患者。我们最近发现，大剂量的具有生物活性的 1,25-二羟维生素 D（1,25D）可促进脱髓鞘和再髓鞘模型中环己酮诱导的髓鞘修复。在本研究中，我们定量分析了 5062 种蛋白质，其中有 125 种在 1,25D 治疗的小鼠再髓鞘过程中的脑组织中与安慰剂相比存在差异调节。在早期再髓鞘阶段上调的蛋白质参与钙结合，例如钙结合蛋白（calretinin，>1.3 倍，p<0.005）、S10A5 和分泌素，以及涉及线粒体功能，例如 NADH-泛醌氧化还原酶链 3 和酰基辅酶 A 合成酶。使用免疫组织化学方法对 calretinin、S10A5 和分泌素的表达水平进行了表征。在早期再髓鞘阶段，1,25D 治疗的小鼠中，中隔核的 calretinin 免疫反应性显著增加（>3 倍，p=0.016）。我们的结果表明，维生素 D 可能通过增加 calretinin 表达和潜在的其他钙结合蛋白的机制来影响髓鞘修复。
