title: Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period.
abstract: 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.
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiao L
authors.initials: XL
authors.lastname: Zhan
authors.affiliation: Battalion 14 of Cadet Brigade, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zi Y
authors.initials: ZY
authors.lastname: Ma
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xing S
authors.initials: XS
authors.lastname: Chen
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qi Y
authors.initials: QY
authors.lastname: Cai
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing 400038, China Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China yaozhx@yahoo.com yaozhx@hotmail.com.
authors.forename: Zhong X
authors.initials: ZX
authors.lastname: Yao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001369:Axons / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000503:physiopathology; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology; D013963:Thyroid Hormones / Q000502:physiology / Q000627:therapeutic use*
chemical_list: D013963:Thyroid Hormones; D003471:Cuprizone
keywords: Thyroid hormone; corpus callosum; multiple sclerosis; myelin; oligodendrocyte