2. Academic Validation
  3. Solifenacin promotes remyelination in cuprizone mouse model by inhibiting the Wnt/β-catenin signaling pathway

Solifenacin promotes remyelination in cuprizone mouse model by inhibiting the Wnt/β-catenin signaling pathway

  • J Chem Neuroanat. 2023 Dec 18:102375. doi: 10.1016/j.jchemneu.2023.102375.
Xinqi Xu 1,  Xueli Song 2,  Fei Chen 1,  Weixing Yan 2,  Qiqi Meng 2,  Jinfeng Liu 3,  Ruiqin Yao 2,  Yaping Liu 4,  Fuxing Dong 5
Affiliations

Affiliations

  • 1 The First Clinical College, Xuzhou Medical University, Xuzhou, 221004, Jiangsu Province, China.
  • 2 Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu Province, China.
  • 3 School of Life Science, Xuzhou Medical University, Xuzhou, 221004, Jiangsu Province, China.
  • 4 National Demonstration Center for Experimental Basic Medical Science Education (Xuzhou Medical University), Xuzhou, 221004, Jiangsu Province, China.
  • 5 Public Experimental Research Center, Xuzhou Medical University, Xuzhou, 221004, Jiangsu Province, China. Electronic address: [email protected].
PMID: 38123002 DOI: 10.1016/j.jchemneu.2023.102375
Abstract

Demyelinating diseases are a type of neurological disorder characterized by the damage to the myelin sheath in the nervous system. Promoting the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) is crucial for treatment. Non-selective muscarinic receptor (MR) antagonists have been shown to improve remyelination in rodent models, although the mechanisms are still unclear. In this study, we treated cuprizone (CPZ) mouse models with different concentrations of Solifenacin (Sol), a selective M3 receptor blocker, to determine the optimal concentration for promoting remyelination. Behavioral tests and Luxol fast blue (LFB) staining were used to observe the extent of remyelination, while immunofluorescence was used to measure the expression levels of myelin-related proteins, including myelin basic protein (MBP) and platelet-derived growth factor receptor alpha (PDGFRα). Western blot analysis was employed to analyze the expression levels of molecules associated with the Wnt/β-catenin signaling pathway. The results showed that Sol treatment significantly promoted myelin regeneration and OPCs differentiation in CPZ-induced mouse models. Additionally, Sol treatment inhibited the Wnt/β-catenin signaling pathway and reversed the effects of CPZ on OPCs differentiation. In conclusion, Sol may promote the differentiation of OPCs by inhibiting the Wnt/β-catenin signaling pathway, making it a potential therapeutic option for central demyelinating diseases.

Keywords

Demyelinating; Solifenacin; Wnt/β-catenin; differentiation; oligodendrocyte precursor cells.

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