Clearing the corpses: regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain.
Clearing the corpses: regulatory mechanisms, novel tools, and therapeutic potential of harnessing microglial phagocytosis in the diseased brain.
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DOI：
10.4103/1673-5374.193220
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发表时间：
2016-10
影响因子：
6.1
通讯作者：
Sierra A
中科院分区：
文献类型：
--
作者：
Diaz-Aparicio I;Beccari S;Abiega O;Sierra A
细胞凋亡是一种广泛存在于脑内的生理和病理现象。死细胞必须被迅速清除，以避免它们在实质中产生进一步的毒性作用，这是由小胶质细胞（大脑专业吞噬细胞）执行的一个过程。虽然吞噬作用是维持组织稳态的关键，但长期以来一直被忽视或间接评估基于小胶质细胞形态，经典活化标志物的表达或体外人工吞噬靶点的吞噬。然而，这些间接方法存在一些局限性，因此，直接观察和定量小胶质细胞吞噬作用仍然是必要的，以充分掌握其在患病大脑中的相关性。为了克服这些注意事项，并获得一个全面的，定量的小胶质细胞吞噬作用的图片，我们已经开发了一套新的参数。这些参数使我们能够确定小胶质细胞利用不同的策略来科普兴奋性毒性或炎症诱导的凋亡挑战。相比之下，我们发现在小鼠和人类癫痫中，小胶质细胞未能找到并吞噬凋亡细胞，导致碎片和炎症的积累。在此，我们主张在神经退行性疾病和神经系统疾病中应常规测试小胶质细胞吞噬作用的效率，以确定其对这些疾病中发现的细胞凋亡和炎症的贡献程度。最后，我们的研究结果指出，增强小胶质细胞吞噬作用是一种新的治疗策略，可以控制组织损伤和炎症，并加速脑部疾病的恢复。
Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro. Nevertheless, these indirect methods present several limitations and, thus, direct observation and quantification of microglial phagocytosis is still necessary to fully grasp its relevance in the diseased brain. To overcome these caveats and obtain a comprehensive, quantitative picture of microglial phagocytosis we have developed a novel set of parameters. These parameters have allowed us to identify the different strategies utilized by microglia to cope with apoptotic challenges induced by excitotoxicity or inflammation. In contrast, we discovered that in mouse and human epilepsy microglia failed to find and engulf apoptotic cells, resulting in accumulation of debris and inflammation. Herein, we advocate that the efficiency of microglial phagocytosis should be routinely tested in neurodegenerative and neurological disorders, in order to determine the extent to which it contributes to apoptosis and inflammation found in these conditions. Finally, our findings point towards enhancing microglial phagocytosis as a novel therapeutic strategy to control tissue damage and inflammation, and accelerate recovery in brain diseases.
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影响因子：
6.2
作者：
Luo, Cong;Koyama, Ryuta;Ikegaya, Yuji
通讯作者：
Ikegaya, Yuji
发育中的大鼠小脑中小胶质细胞的形态和吞噬性。
影响因子：
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作者：
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作者：
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通讯作者：
Tzeng, Shun-Fen
影响因子：
2.5
作者：
Dayer, AG;Ford, AA;Cameron, HA
通讯作者：
Cameron, HA