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小胶质细胞耗竭方法在中枢神经系统病理状况中的作用

The Role of Microglial Depletion Approaches in Pathological Condition of CNS.

作者信息

Tahmasebi Fatemeh, Barati Shirin

机构信息

Department of Anatomy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Anatomy, Saveh University of Medical Sciences, Saveh, Iran.

出版信息

Cell Mol Neurobiol. 2023 Aug;43(6):2459-2471. doi: 10.1007/s10571-023-01326-8. Epub 2023 Feb 4.

Abstract

Microglia are the primary immune cells of the central nervous system (CNS) that comprise about 5-12% of all cells in the brain. These cells are the first line of defense that protects the CNS from damage and attacking pathogens. Microglia originate from yolk sac macrophages and migrate to the brain before the blood-brain barrier formation. Microglia show key roles in healthy CNS including promoting neurogenesis, synaptic sculpting, and maintaining homeostasis but in pathological conditions of CNS, microglial activation may exacerbate diseases. Thus, microglial depletion of the CNS is a novel approach that could be a useful tool to understand the microglial functions in neurodegenerative and neuroinflammatory diseases. There are methods for microglial ablation and reduction such as genetic tools and pharmacological inhibitors. In this study, we review recent studies that used different microglial ablation models for microglial reduction and repopulation after depletion in pathological states of CNS. Recently, studies showed that microglial depletion as a potential therapeutic application has benefits (such as inflammatory factors reduction, increase synaptogenesis, astrogliosis preventation) in CNS. For these reasons, the inhibition of microglia with these models was considered a therapeutic approach for neurodegenerative disease treatment.

摘要

小胶质细胞是中枢神经系统(CNS)的主要免疫细胞,约占大脑所有细胞的5-12%。这些细胞是保护中枢神经系统免受损伤和病原体侵袭的第一道防线。小胶质细胞起源于卵黄囊巨噬细胞,并在血脑屏障形成之前迁移至大脑。小胶质细胞在健康的中枢神经系统中发挥着关键作用,包括促进神经发生、突触重塑和维持体内平衡,但在中枢神经系统的病理状态下,小胶质细胞的激活可能会加重疾病。因此,中枢神经系统中小胶质细胞的耗竭是一种新方法,可能是了解小胶质细胞在神经退行性疾病和神经炎症性疾病中功能的有用工具。有多种用于小胶质细胞消融和减少的方法,如基因工具和药理学抑制剂。在本研究中,我们综述了最近的一些研究,这些研究在中枢神经系统病理状态下使用不同的小胶质细胞消融模型来减少小胶质细胞数量并使其在耗竭后重新填充。最近,研究表明,小胶质细胞耗竭作为一种潜在的治疗应用,在中枢神经系统中具有益处(如减少炎症因子、增加突触发生、预防星形胶质细胞增生)。基于这些原因,用这些模型抑制小胶质细胞被认为是治疗神经退行性疾病的一种方法。

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