Remyelination is enhanced by Astragalus polysaccharides through inducing the differentiation of oligodendrocytes from neural stem cells in cuprizone model of demyelination
Remyelination is enhanced by Astragalus polysaccharides through inducing the differentiation of oligodendrocytes from neural stem cells in cuprizone model of demyelination
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DOI：
10.1016/j.brainres.2021.147459
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发表时间：
2021-03
期刊：
影响因子：
2.9
通讯作者：
N. Ye;J. Cruz;Xiaoyan Peng;Jinyun Ma;Ai-Ming Zhang;Xiaodong Cheng
中科院分区：
文献类型：
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作者：
N. Ye;J. Cruz;Xiaoyan Peng;Jinyun Ma;Ai-Ming Zhang;Xiaodong Cheng
脱髓鞘是多发性硬化症的标志。促进髓鞘再生是治疗多发性硬化症的重要策略。我们前期的研究表明，黄芪的主要生物活性成分黄芪多糖(APS)对实验性自身免疫性脑脊髓炎小鼠脱髓鞘有一定的预防作用。为了探讨黄芪多糖对小鼠脱髓鞘的影响及其机制，本研究建立了铜试剂诱导的小鼠脱髓鞘模型，并对其进行了治疗。结果表明，黄芪多糖可减轻脱髓鞘所致的神经行为功能障碍，并能有效促进体内髓鞘再生。为探讨促进再髓鞘形成的机制是否与神经干细胞的分化有关，采用实时荧光定量聚合酶链式反应、免疫印迹和免疫组织化学方法，检测了小鼠痂状体组织中神经干细胞、星形胶质细胞、少突胶质细胞和神经元的生物标志物。结果表明，黄芪多糖抑制神经干细胞的干性，减少神经干细胞向星形胶质细胞的分化，促进神经干细胞向少突胶质细胞和神经元的分化。这一现象在体外培养的C17.2神经干细胞分化模型中得到了证实。由于Sonic hedgehog信号通路在神经干细胞分化为少突胶质细胞过程中起关键作用，我们在体内和体外检测了该通路中关键分子的表达水平，最终发现APS激活了这一信号通路。综上所述，APS可能首先激活Sonic Hedgehog信号通路，然后诱导NSCs分化为少突胶质细胞，并促进再髓鞘形成，提示APS可能是治疗MS的潜在候选细胞。
Demyelination is the hallmark of multiple sclerosis (MS). Promoting remyelination is an important strategy to treat MS. Our previous study showed thatAstragalus polysaccharides(APS), the main bioactive component ofAstragalus membranaceus, could prevent demyelination in experimental autoimmune encephalomyelitis mice. To investigate the effects of APS on remyelination and the underlying mechanisms, in this study we set up a cuprizone-induced demyelination model in mice and treated them with APS. It was found that APS relieved the neurobehavioral dysfunctions caused by demyelination, and efficaciously facilitated remyelinationin vivo. In order to determine whether the mechanism of enhancing remyelination was associated with the differentiation of neural stem cells (NSCs), biomarkers of NSCs, astrocytes, oligodendrocytes and neurons were measured in the corpus callosum tissues of mice through Real-time PCR, Western blot and immunohistochemistry assays. Data revealed that APS suppressed the stemness of NSCs, reduced the differentiation of NSCs into astrocytes, and promoted the differentiation into oligodendrocytes and neurons. This phenomenon was confirmed in the differentiation model of C17.2 NSCs culturedin vitro.Since Sonic hedgehog signaling pathway has been proven to be crucial to the differentiation of NSCs into oligodendrocytes, we examined expression levels of the key molecules in this pathwayin vivoandin vitro, and eventually found APS activated this signaling pathway. Together, our results demonstrated that APS probably activated Sonic hedgehog signaling pathway first, then induced NSCs to differentiate into oligodendrocytes and promoted remyelination, which suggested that APS might be a potential candidate in treating MS.