Dietary cholesterol promotes repair of demyelinated lesions in the adult brain.
Dietary cholesterol promotes repair of demyelinated lesions in the adult brain.
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DOI：
10.1038/ncomms14241
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发表时间：
2017-01-24
影响因子：
16.6
通讯作者：
Saher G
中科院分区：
文献类型：
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作者：
Berghoff SA;Gerndt N;Winchenbach J;Stumpf SK;Hosang L;Odoardi F;Ruhwedel T;Böhler C;Barrette B;Stassart R;Liebetanz D;Dibaj P;Möbius W;Edgar JM;Saher G
多发性硬化症（MS）是一种炎性脱髓鞘疾病，其中髓鞘再生失败导致持续残疾。胆固醇是发育中的CNS中髓鞘生物合成的限速因素;然而，胆固醇不足是否会导致MS中髓鞘再生失败尚不清楚。在这里，我们展示了脱髓鞘和髓鞘再生小鼠模型中胆固醇、髓鞘形成和神经学参数之间的关系。在铜腙模型中，急性疾病降低血清胆固醇水平，可以通过饮食胆固醇恢复。伴随着血脑屏障损伤，补充胆固醇直接支持少突胶质细胞前体增殖和分化，并恢复生长因子的平衡，创造一个允许的修复环境。这导致轴突损伤减弱，髓鞘再生增强和运动学习改善。值得注意的是，在实验性自身免疫性脑脊髓炎中，胆固醇补充剂不会加剧疾病表达。这些发现强调了饮食胆固醇在炎症性疾病中的安全性，并指出了胆固醇在促进脱髓鞘事件后修复中的先前未被认识的作用。胆固醇在发育过程中对轴突髓鞘形成很重要。在这里，作者表明，在多发性硬化症的cuprizone小鼠模型中，胆固醇水平降低，并且饮食胆固醇补充剂增强髓鞘再生和恢复。
Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes. Cholesterol is important for axonal myelination during development. Here the authors show that cholesterol levels are reduced in a cuprizone mouse model of multiple sclerosis and that dietary cholesterol supplementation enhances remyelination and recovery.