Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany.
Int J Mol Sci. 2023 Nov 16;24(22):16420. doi: 10.3390/ijms242216420.
A diverse array of neurological and psychiatric disorders, including multiple sclerosis, Alzheimer's disease, and schizophrenia, exhibit distinct myelin abnormalities at both the molecular and histological levels. These aberrations are closely linked to dysfunction of oligodendrocytes and alterations in myelin structure, which may be pivotal factors contributing to the disconnection of brain regions and the resulting characteristic clinical impairments observed in these conditions. Astrocytes, which significantly outnumber neurons in the central nervous system by a five-to-one ratio, play indispensable roles in the development, maintenance, and overall well-being of neurons and oligodendrocytes. Consequently, they emerge as potential key players in the onset and progression of a myriad of neurological and psychiatric disorders. Furthermore, targeting astrocytes represents a promising avenue for therapeutic intervention in such disorders. To gain deeper insights into the functions of astrocytes in the context of myelin-related disorders, it is imperative to employ appropriate in vivo models that faithfully recapitulate specific aspects of complex human diseases in a reliable and reproducible manner. One such model is the cuprizone model, wherein metabolic dysfunction in oligodendrocytes initiates an early response involving microglia and astrocyte activation, culminating in multifocal demyelination. Remarkably, following the cessation of cuprizone intoxication, a spontaneous process of endogenous remyelination occurs. In this review article, we provide a historical overview of studies investigating the responses and putative functions of astrocytes in the cuprizone model. Following that, we list previously published works that illuminate various aspects of the biology and function of astrocytes in this multiple sclerosis model. Some of the studies are discussed in more detail in the context of astrocyte biology and pathology. Our objective is twofold: to provide an invaluable overview of this burgeoning field, and, more importantly, to inspire fellow researchers to embark on experimental investigations to elucidate the multifaceted functions of this pivotal glial cell subpopulation.
一系列不同的神经和精神疾病，包括多发性硬化症、阿尔茨海默病和精神分裂症，在分子和组织学水平上都表现出明显的髓鞘异常。这些异常与少突胶质细胞功能障碍和髓鞘结构改变密切相关，这可能是导致大脑区域连接中断以及这些疾病中观察到的特征性临床损伤的关键因素。星形胶质细胞在中枢神经系统中的数量比神经元多五倍，在神经元和少突胶质细胞的发育、维持和整体健康中发挥着不可或缺的作用。因此，它们成为许多神经和精神疾病发生和发展的潜在关键因素。此外，针对星形胶质细胞可能是治疗这些疾病的一种有前途的方法。为了更深入地了解星形胶质细胞在髓鞘相关疾病中的功能，必须使用适当的体内模型，以可靠和可重复的方式真实地再现复杂人类疾病的特定方面。其中一种模型是杯状蛋白模型，其中少突胶质细胞的代谢功能障碍引发了一个早期反应，涉及小胶质细胞和星形胶质细胞的激活，最终导致多灶性脱髓鞘。值得注意的是，在停止杯状蛋白中毒后，会发生自发的内源性髓鞘再生过程。在这篇综述文章中，我们提供了一个历史概述，研究了星形胶质细胞在杯状蛋白模型中的反应和潜在功能。在那之后，我们列出了以前发表的阐明星形胶质细胞在这个多发性硬化症模型中的生物学和功能的各个方面的工作。其中一些研究在星形胶质细胞生物学和病理学的背景下进行了更详细的讨论。我们的目标有两个：提供对这个新兴领域的宝贵概述，更重要的是，激励其他研究人员进行实验研究，以阐明这个关键的神经胶质细胞亚群的多方面功能。
