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

Research output: Contribution to journalArticle

38 Citations (Scopus)

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

Fingerprint

ischemia
Phagocytes
Brain Ischemia
Astrocytes
brain
Brain
penumbras
Ischemia
disrupting
phenotype
Phagocytosis
Up-Regulation
molecules
inclusions
Molecules
Microglia
augmentation
Tissue
Phenotype
Wounds and Injuries

ASJC Scopus subject areas

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

Cite this

Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway. / Morizawa, Yosuke M.; Hirayama, Yuri; Ohno, Noubuhiko; Shibata, Shinsuke; Shigetomi, Eiji; Sui, Yang; Nabekura, Junichi; Sato, Koichi; Okajima, Fumikazu; Takebayashi, Hirohide; Okano, Hideyuki; Koizumi, Schuichi.

In: Nature Communications, Vol. 8, No. 1, 28, 01.12.2017.

Research output: Contribution to journalArticle

Morizawa, YM, 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, vol. 8, no. 1, 28. https://doi.org/10.1038/s41467-017-00037-1
Morizawa, Yosuke M. ; Hirayama, Yuri ; Ohno, Noubuhiko ; Shibata, Shinsuke ; Shigetomi, Eiji ; Sui, Yang ; Nabekura, Junichi ; Sato, Koichi ; Okajima, Fumikazu ; Takebayashi, Hirohide ; Okano, Hideyuki ; Koizumi, Schuichi. / Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway. In: Nature Communications. 2017 ; Vol. 8, No. 1.
@article{72f0a329252d4933a0ca10c3272102dc,
title = "Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway",
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.",
author = "Morizawa, {Yosuke M.} and Yuri Hirayama and Noubuhiko Ohno and Shinsuke Shibata and Eiji Shigetomi and Yang Sui and Junichi Nabekura and Koichi Sato and Fumikazu Okajima and Hirohide Takebayashi and Hideyuki Okano and Schuichi Koizumi",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41467-017-00037-1",
language = "English",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85021226208&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021226208&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-00037-1

DO - 10.1038/s41467-017-00037-1

M3 - Article

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 28

ER -