甲状腺激素通过其在缓解期髓鞘再生中的作用减轻了由铜离子螯合剂诱导的脱髓鞘。
Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period.
作者信息
Zhang Mao, Zhan Xiao L, Ma Zi Y, Chen Xing S, Cai Qi Y, Yao Zhong X
机构信息
Department of Physiology, Third Military Medical University, Chongqing 400038, China.
Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China.
出版信息
Exp Biol Med (Maywood). 2015 Sep;240(9):1183-96. doi: 10.1177/1535370214565975. Epub 2015 Jan 10.
Multiple sclerosis (MS) is a disease induced by demyelination in the central nervous system, and the remission period of MS is crucial for remyelination. In addition, abnormal levels of thyroid hormone (TH) have been identified in MS. However, in the clinic, insufficient attention has been paid to the role of TH in the remission period. Indeed, TH not only functions in the development of the brain but also affects myelination. Therefore, it is necessary to observe the effect of TH on remyelination during this period. A model of demyelination induced by cuprizone (CPZ) was used to observe the function of TH in remyelination during the remission period of MS. Through weighing and behavioral tests, we found that TH improved the physical symptoms of mice impaired by CPZ. Supplementation of TH led to the repair of myelin as detected by immunohistochemistry and western blot. In addition, a sufficient TH supply resulted in an increase in myelinated axons without affecting myelin thickness and g ratio in the corpus callosum, as detected by electron microscopy. Double immunostaining with myelin basic protein and neurofilament 200 (NF200) showed that the CPZ-induced impairment of axons was alleviated by TH. Conversely, insufficient TH induced by 6-propyl-2-thiouracil resulted in the enlargement of mitochondria. Furthermore, we found that an adequate supply of TH promoted the proliferation and differentiation of oligodendrocyte lineage cells by immunofluorescence, which was beneficial to remyelination. Further, we found that TH reduced the number of astrocytes without affecting microglia. Conclusively, it was shown that TH alleviated demyelination induced by CPZ by promoting the development of oligodendrocyte lineage cells and remyelination. The critical time for remyelination is the remission period of MS. TH plays a significant role in alleviating demyelination during the remission period in the clinical treatment of MS.
多发性硬化症（MS）是一种由中枢神经系统脱髓鞘引起的疾病，MS的缓解期对髓鞘再生至关重要。此外，已在MS中发现甲状腺激素（TH）水平异常。然而，在临床上，TH在缓解期的作用尚未得到足够重视。事实上，TH不仅在大脑发育中起作用，还影响髓鞘形成。因此，有必要在此期间观察TH对髓鞘再生的影响。使用由铜螯合剂（CPZ）诱导的脱髓鞘模型来观察TH在MS缓解期髓鞘再生中的作用。通过称重和行为测试，我们发现TH改善了受CPZ损害的小鼠的身体症状。免疫组织化学和蛋白质印迹检测显示，补充TH导致髓鞘修复。此外，电子显微镜检测显示，充足的TH供应导致胼胝体中有髓轴突增加，而不影响髓鞘厚度和g比值。用髓鞘碱性蛋白和神经丝200（NF200）进行双重免疫染色显示，TH减轻了CPZ诱导的轴突损伤。相反，由6-丙基-2-硫氧嘧啶诱导的TH不足导致线粒体增大。此外，我们发现充足的TH供应通过免疫荧光促进少突胶质细胞系细胞的增殖和分化，这有利于髓鞘再生。此外，我们发现TH减少了星形胶质细胞的数量，而不影响小胶质细胞。总之，结果表明TH通过促进少突胶质细胞系细胞的发育和髓鞘再生减轻了CPZ诱导的脱髓鞘。髓鞘再生的关键时期是MS的缓解期。TH在MS临床治疗的缓解期减轻脱髓鞘中起重要作用。
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