Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function  

作　　者：Jing-xian Sun Ke-ying Zhu Yu-meng Wang Dan-jie Wang Mi-zhen Zhang Heela Sarlus Irene Benito-Cuesta Xiao-qiang Zhao Zao-feng Zou Qing-yang Zhong Yi Feng Shuai Wu Yan-qing Wang Robert A.Harris Jun Wang 

机构地区：[1]Department of Integrative Medicine and Neurobiology,School of Basic Medical Science,Institutes of Integrative Medicine,State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Shanghai Medical College,Fudan University,Shanghai 200032,China [2]Department of Clinical Neuroscience,Karolinska Institutet,Center for Molecular Medicine,Karolinska University Hospital at Solna,Stockholm,Sweden [3]Department of General Surgery,Jiading Hospital of Traditional Chinese Medicine,Shanghai 201800,China [4]Department of Neurology,Zhongshan Hospital,Fudan University,Shanghai 200032,China

出　　处：《Acta Pharmacologica Sinica》2023年第4期766-779,共14页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82074538,81671597);the Innovative Research Team of High-Level Local Universities in Shanghai(2019-2023);the Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01);the Development Project of Shanghai Peak Disciplines-Integrated Chinese and Western Medicine.KZ was sponsored by China Scholarship Council(201700260280).

摘　　要：The transient receptor potential vanilloid 1(TRPV1)is a non-selective cation channel that is activated by capsaicin(CAP),the main component of chili pepper.Despite studies in several neurological diseases,the role of TRPV1 in demyelinating diseases remains unknown.Herein,we reported that TRPV1 expression was increased within the corpus callosum during demyelination in a cuprizone(CPZ)-induced demyelination mouse model.TRPV1 deficiency exacerbated motor coordinative dysfunction and demyelination in CPZ-treated mice,whereas the TRPV1 agonist CAP improved the behavioral performance and facilitated remyelination.TRPV1 was predominantly expressed in Iba1+microglia/macrophages in human brain sections of multiple sclerosis patients and mouse corpus callosum under demyelinating conditions.TRPV1 deficiency decreased microglial recruitment to the corpus callosum,with an associated increase in the accumulation of myelin debris.Conversely,the activation of TRPV1 by CAP enhanced the recruitment of microglia to the corpus callosum and potentiated myelin debris clearance.Using real-time live imaging we confirmed an increased phagocytic function of microglia following CAP treatment.In addition,the expression of the scavenger receptor CD36 was increased,and that of the glycolysis regulators Hif1a and Hk2 was decreased.We conclude that TRPV1 is an important regulator of microglial function in the context of demyelination and may serve as a promising therapeutic target for demyelinating diseases such as multiple sclerosis.

关 键 词：TRPV1 CAPSAICIN microglia REMYELINATION phagocytosis 

分 类 号：R285.5[医药卫生—中药学]