TY - JOUR
T1 - Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway
AU - Morizawa, Yosuke M.
AU - Hirayama, Yuri
AU - Ohno, Noubuhiko
AU - Shibata, Shinsuke
AU - Shigetomi, Eiji
AU - Sui, Yang
AU - Nabekura, Junichi
AU - Sato, Koichi
AU - Okajima, Fumikazu
AU - Takebayashi, Hirohide
AU - Okano, Hideyuki
AU - Koizumi, Schuichi
N1 - Funding Information:
This work was supported by Grants-in-aid for Scientific Research (KAKENHI) on Innovative areas "Glial assembly" (25117003 to S.K.), on Challenging Exploratory Research (15K15524 to S.K.), on Research (B) (16H04669 to S.K.), Grant-in-Aid for JSPS Research Fellow (12J08505 to Y.M.), Grant-in-Aid for Young Scientists (B) (50772167 to Y.M.), Innovative Areas-Resource and technical support platforms for promoting research "Advanced Bioimaging Support" (JP16H06280), the Core Research for Evolutional Science and Technology Grant from the Japan Society for the Promotion of Sciences (to S.K. and J.N.), the Grant for the Cutting Edge Brain Sciences from Univ. Yamanashi, and Grant for Brain/MINDS from AMED (to S.S. and H.O.).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-00037-1
DO - 10.1038/s41467-017-00037-1
M3 - Article
C2 - 28642575
AN - SCOPUS:85021226208
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 28
ER -