Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned.
Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned.
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DOI：
10.3389/fncel.2014.00073
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发表时间：
2014
影响因子：
5.3
通讯作者：
Stangel M
中科院分区：
文献类型：
--
作者：
Gudi V;Gingele S;Skripuletz T;Stangel M
虽然星形胶质细胞增多症和小胶质细胞激活是多发性硬化(MS)和其他中枢神经系统(CNS)损害的特征，但这些事件的确切功能尚不完全清楚。动物模型有助于了解中枢神经系统不同细胞类型之间的复杂相互作用，并揭示髓鞘损伤和修复的一般机制。所谓的铜酮模型是一种中枢神经白质和灰质脱髓鞘的毒性模型，缺乏自身免疫成分。铜可诱导成熟少突胶质细胞的凋亡，导致星形胶质细胞和小胶质细胞的强烈脱髓鞘和深度激活，不同白质和灰质区域之间存在区域异质性。尽管该模型不适用于研究自身免疫介导的脱髓鞘，但对于阐明脱髓鞘，特别是再髓鞘形成的基本细胞和分子机制非常有帮助，而不依赖于与外周免疫细胞的相互作用。吞噬和清除受损的髓鞘似乎是小胶质细胞在该模型中的主要作用之一，众所周知，清除髓鞘碎片是成功再髓鞘形成的先决条件。此外，小胶质细胞提供了几个信号来支持重新髓鞘形成。星形胶质细胞在脱髓鞘和再髓鞘形成过程中的作用尚不清楚。既有支持性的，也有破坏性的功能。使用铜试剂模型，我们可以证明星形胶质细胞和小胶质细胞之间存在着重要的串扰。在这篇综述中，我们重点讨论了神经胶质反应和相互作用在铜试剂模型中的作用。与其他动物模型相比，对人类疾病多发性硬化症的优点和局限性以及其潜在的治疗相关性进行了关键的讨论。
Although astrogliosis and microglia activation are characteristic features of multiple sclerosis (MS) and other central nervous system (CNS) lesions the exact functions of these events are not fully understood. Animal models help to understand the complex interplay between the different cell types of the CNS and uncover general mechanisms of damage and repair of myelin sheaths. The so called cuprizone model is a toxic model of demyelination in the CNS white and gray matter, which lacks an autoimmune component. Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions. Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells. Phagocytosis and removal of damaged myelin seems to be one of the major roles of microglia in this model and it is well known that removal of myelin debris is a prerequisite of successful remyelination. Furthermore, microglia provide several signals that support remyelination. The role of astrocytes during de- and remyelination is not well defined. Both supportive and destructive functions have been suggested. Using the cuprizone model we could demonstrate that there is an important crosstalk between astrocytes and microglia. In this review we focus on the role of glial reactions and interaction in the cuprizone model. Advantages and limitations of as well as its potential therapeutic relevance for the human disease MS are critically discussed in comparison to other animal models.
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DOI：
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影响因子：
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