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Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway.
Nature Communications ( IF 14.7 ) Pub Date : 2017-06-22 , DOI: 10.1038/s41467-017-00037-1
Yosuke M. Morizawa , Yuri Hirayama , Nobuhiko Ohno , Shinsuke Shibata , Eiji Shigetomi , Yang Sui , Junichi Nabekura , Koichi Sato , Fumikazu Okajima , Hirohide Takebayashi , Hideyuki Okano , Schuichi Koizumi

Astrocytes become reactive following various brain insults; however, the functions of reactive astrocytes are poorly understood. Here, we show that reactive astrocytes function as phagocytes after transient ischemic injury and appear in a limited spatiotemporal pattern. Following transient brain ischemia, phagocytic astrocytes are observed within the ischemic penumbra region during the later stage of ischemia. However, phagocytic microglia are mainly observed within the ischemic core region during the earlier stage of ischemia. Phagocytic astrocytes upregulate ABCA1 and its pathway molecules, MEGF10 and GULP1, which are required for phagocytosis, and upregulation of ABCA1 alone is sufficient for enhancement of phagocytosis in vitro. Disrupting ABCA1 in reactive astrocytes result in fewer phagocytic inclusions after ischemia. Together, these findings suggest that astrocytes are transformed into a phagocytic phenotype as a result of increase in ABCA1 and its pathway molecules and contribute to remodeling of damaged tissues and penumbra networks.Astrocytic phagocytosis has been shown to play a role in synaptic pruning during development, but whether adult astrocytes possess phagocytic ability is unclear. Here the authors show that following brain ischemia, reactive astrocytes become phagocytic and engulf debris via the ABCA1 pathway.

中文翻译:

反应性星形胶质细胞通过ABCA1介导的途径在脑缺血后起吞噬细胞的作用。

在各种脑损伤后,星形胶质细胞开始发生反应。然而,人们对反应性星形胶质细胞的功能了解甚少。在这里,我们显示反应性星形胶质细胞在短暂性脑缺血损伤后起吞噬细胞的作用,并以有限的时空模式出现。短暂性脑缺血后,在缺血的后期阶段,在缺血半影区域内观察到吞噬性星形胶质细胞。然而,吞噬小胶质细胞主要在缺血的早期阶段在缺血核心区域内观察到。吞噬性星形胶质细胞上调吞噬作用所需的ABCA1及其通路分子MEGF10和GULP1,而单独ABCA1的上调足以增强体外吞噬作用。在反应性星形胶质细胞中破坏ABCA1导致缺血后较少的吞噬性包裹体。一起,这些发现表明,星形胶质细胞由于ABCA1及其途径分子的增加而转化为吞噬表型,并有助于受损组织和半影网的重塑。星形胶质吞噬作用已显示在发育过程中对突触修剪有作用,但是否成年星形胶质细胞是否具有吞噬能力尚不清楚。作者在这里表明,在脑缺血后,反应性星形胶质细胞会通过ABCA1途径吞噬并吞噬碎片。但尚不清楚成人星形胶质细胞是否具有吞噬能力。作者在这里表明,在脑缺血后,反应性星形胶质细胞会通过ABCA1途径吞噬并吞噬碎片。但尚不清楚成人星形胶质细胞是否具有吞噬能力。作者在这里表明,在脑缺血后,反应性星形胶质细胞会通过ABCA1途径吞噬并吞噬碎片。
更新日期:2017-06-26
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