An updated assessment of microglia depletion: current concepts and future directions.
An updated assessment of microglia depletion: current concepts and future directions.
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DOI：
10.1186/s13041-017-0307-x
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发表时间：
2017-06-19
期刊：
影响因子：
3.6
通讯作者：
Zhang XM
中科院分区：
文献类型：
--
作者：
Han J;Harris RA;Zhang XM
小胶质细胞是中枢神经系统中主要的常驻免疫细胞，并且被认为在炎症和生理环境中是多功能的参与者。一方面，为了保护微环境，小胶质细胞可以通过与微生物产物或细胞碎片接触而被快速激活，从而通过吞噬作用和分泌细胞因子和趋化因子来发挥先天免疫功能。相反，小胶质细胞也可以通过产生神经营养因子和清除髓鞘碎片来帮助大脑发育、突触可塑性和神经修复。小胶质细胞的功能障碍和小胶质细胞诱导的神经炎症与许多神经系统疾病的发生和发展有关。虽然过去十年在理解多任务小胶质细胞方面取得了重大进展，但在很大程度上仍然是一个谜，即小胶质细胞在不同疾病阶段的相对重要性以及如何靶向小胶质细胞以获得最佳治疗效果。值得注意的是，通过基因靶向或药物治疗的小胶质细胞耗竭可以被视为刺激新的小胶质细胞重新填充中枢神经系统的有效工具。在各种实验动物模型疾病的定义阶段，小胶质细胞耗竭和随后的再增殖使我们能够扩展我们对分子机制的了解，从而为设计解决神经炎症和促进恢复的策略带来希望。在此，我们强调了小胶质细胞的高度可塑性和多样性表型，并概述了从小胶质细胞耗竭方法中吸取的教训。
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris. It is now well accepted that the dysfunction of microglia and microglia-induced neuroinflammation are implicated in the occurrence and progression of many neurological diseases. Although the past decade has witnessed major progress in understanding of multi-tasking microglia, what remains largely enigmatic is the relative importance of microglia at different disease stages and how microglia should be targeted for optimal therapeutic efficacy. Notably, microglia depletion through genetic targeting or pharmacological therapies can be viewed as effective tools to stimulate new microglia to repopulate the central nervous system. Microglia depletion and subsequent repopulation at defined stages in various experimental animal model disorders allow us to extend our knowledge of molecular mechanisms, thus holding promise for designing strategies to resolve neuroinflammation and promote recovery. Herein we highlight the highly plastic and diverse phenotypes of microglia and outline the lessons learned from microglia depletion approaches.