The Mouse Model of Internal Capsule Demyelination: A Novel Tool for Investigating Motor Functional Changes Caused by Demyelination and for Evaluating Drugs That Promote Remyelination

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-02-23 DOI:10.1267/ahc.24-00005

Reiji Yamazaki, Nobuhiko Ohno

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Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterized by remyelination failure and axonal dysfunction. Remyelination by oligodendrocytes is critical for improvement of neurological deficits associated with demyelination. Rodent models of demyelination are frequently used to develop and evaluate therapies for MS. However, a suitable mouse model for assessing remyelination-associated recovery of motor functions is currently unavailable. In this review, we describe the development of the mouse model of internal capsule (IC) demyelination by focal injection of lysolecithin into brain and its application in the evaluation of drugs for demyelinating diseases. This mouse model exhibits motor deficits and subsequent functional recovery accompanying IC remyelination. Notably, this model shows enhancement of functional recovery as well as tissue regeneration when treated with clemastine, a drug that promotes remyelination. The IC demyelination mouse model should contribute to the development of novel drugs that promote remyelination and ameliorate neurological deficits in demyelinating diseases.

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内囊脱髓鞘小鼠模型：研究脱髓鞘引起的运动功能变化和评估促进脱髓鞘药物的新工具

多发性硬化症（MS）是中枢神经系统的一种炎症性脱髓鞘疾病，以再髓鞘化失败和轴突功能障碍为特征。少突胶质细胞的再髓鞘化对改善脱髓鞘引起的神经功能缺损至关重要。脱髓鞘的啮齿动物模型常用于开发和评估多发性硬化症的疗法。然而，目前还没有合适的小鼠模型来评估与再髓鞘化相关的运动功能恢复情况。在这篇综述中，我们介绍了通过向大脑局灶性注射溶血卵磷脂而建立的内囊（IC）脱髓鞘小鼠模型，以及该模型在脱髓鞘疾病药物评估中的应用。这种小鼠模型表现出运动障碍，随后伴随着内囊脱髓鞘的功能恢复。值得注意的是，该模型在使用促进再髓鞘化的药物氯马斯汀（clemastine）治疗后，功能恢复和组织再生均有所增强。集成电路脱髓鞘小鼠模型有助于开发促进脱髓鞘再形成和改善脱髓鞘疾病神经功能缺损的新型药物。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.