Abstract：
Demyelinating diseases are a type of neurological disorder characterized by the damage to the myelin sheath in the central 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)-induced demyelination mouse model with different concentrations of Solifenacin (Sol), a selective M3 receptor antagonist, 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 (PDGFR-α). 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 demyelination mouse model. 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 nervous system demyelinating diseases.
摘要：
脱髓鞘疾病是一种神经系统疾病，其特征是神经系统中髓鞘的损伤。促进少突胶质细胞前体细胞（OPCs）的增殖和分化对于治疗至关重要。非选择性毒蕈碱受体（MR）拮抗剂已被证明可以改善啮齿动物模型中的髓鞘再生，尽管机制尚不清楚。在这项研究中,我们用不同浓度的索利那新（Sol）处理铜（CPZ）小鼠模型，选择性M3受体阻断剂,以确定促进髓鞘再生的最佳浓度。使用行为测试和Luxol坚固蓝（LFB）染色观察髓鞘再生的程度，而免疫荧光用于测量髓鞘相关蛋白的表达水平，包括髓鞘碱性蛋白（MBP）和血小板衍生生长因子受体α（PDGFRα）。采用蛋白质印迹分析来分析与Wnt/β-连环蛋白信号通路相关的分子的表达水平。结果表明,Sol处理显著促进CPZ诱导小鼠模型的髓磷脂再生和OPCs分化。此外,溶胶处理抑制Wnt/β-catenin信号通路并逆转CPZ对OPCs分化的影响。总之,溶胶可能通过抑制Wnt/β-catenin信号通路促进OPCs分化,使其成为中枢脱髓鞘疾病的潜在治疗选择。
