Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway

Yosuke M. Morizawa, Yuri Hirayama, Noubuhiko Ohno, Shinsuke Shibata, Eiji Shigetomi, Yang Sui, Junichi Nabekura, Koichi Sato, Fumikazu Okajima, Hirohide Takebayashi, Hideyuki Okano, Schuichi Koizumi

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Abstract

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.

Original languageEnglish
Article number28
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Morizawa, Y. M., Hirayama, Y., Ohno, N., Shibata, S., Shigetomi, E., Sui, Y., Nabekura, J., Sato, K., Okajima, F., Takebayashi, H., Okano, H., & Koizumi, S. (2017). Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway. Nature Communications, 8(1), [28]. https://doi.org/10.1038/s41467-017-00037-1