TY - JOUR AU - Sun Jing-xian AU - Zhu Ke-ying AU - Wang Yu-meng AU - Wang Dan-jie AU - Zhang Mi-zhen AU - Sarlus Heela AU - Benito-Cuesta Irene AU - Zhao Xiao-qiang AU - Zou Zao-feng AU - Zhong Qing-yang AU - Feng Yi AU - Wu Shuai AU - Wang Yan-qing AU - Harris Robert A. AU - Wang Jun PY - 2023 TI - Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function JF - Acta Pharmacologica Sinica; Vol 44, No 4 (April 2023): Acta Pharmacologica Sinica Y2 - 2023 KW - N2 - 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. UR - http://www.chinaphar.com/article/view/10802