索非那新通过抑制 Wnt/β-catenin 信号通路促进铜绿素小鼠模型的髓鞘再形成

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of chemical neuroanatomy Pub Date : 2023-12-18 DOI:10.1016/j.jchemneu.2023.102375
Xinqi Xu , Xueli Song , Fei Chen , Weixing Yan , Qiqi Meng , Jinfeng Liu , Ruiqin Yao , Yaping Liu , Fuxing Dong
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引用次数: 0

摘要

脱髓鞘疾病是一种以神经系统髓鞘受损为特征的神经系统疾病。促进少突胶质前体细胞(OPC)的增殖和分化对治疗至关重要。非选择性毒蕈碱受体(MR)拮抗剂已被证明能改善啮齿类动物模型中的髓鞘再形成,但其机制仍不清楚。在这项研究中,我们用不同浓度的选择性M3受体阻断剂索利芬那辛(Sol)治疗铜绿素(CPZ)小鼠模型,以确定促进髓鞘再形成的最佳浓度。行为测试和卢克索快蓝(LFB)染色用于观察髓鞘再形成的程度,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)。还采用了 Western 印迹分析法来分析与 Wnt/β-catenin 信号通路相关的分子的表达水平。结果表明,在CPZ诱导的小鼠模型中,溶胶处理能明显促进髓鞘再生和OPCs分化。此外,溶胶还能抑制Wnt/β-catenin信号通路,逆转CPZ对OPCs分化的影响。总之,溶胶可通过抑制Wnt/β-catenin信号通路促进OPCs分化,使其成为治疗中枢性脱髓鞘疾病的潜在疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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.

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来源期刊
Journal of chemical neuroanatomy
Journal of chemical neuroanatomy 医学-神经科学
CiteScore
4.50
自引率
3.60%
发文量
87
审稿时长
62 days
期刊介绍: The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches. Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples. The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
期刊最新文献
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