Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation

Abstract Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitoc...

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Autores principales:	Mitsuhiko Katoh, Bao Wu, Huy Bang Nguyen, Truc Quynh Thai, Ryo Yamasaki, Haiyan Lu, Anna M. Rietsch, Musab M. Zorlu, Youichi Shinozaki, Yurika Saitoh, Sei Saitoh, Takashi Sakoh, Kazuhiro Ikenaka, Schuichi Koizumi, Richard M. Ransohoff, Nobuhiko Ohno
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/52abb5ec19ee44a2bc3a37aaeb839825
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spelling	oai:doaj.org-article:52abb5ec19ee44a2bc3a37aaeb8398252021-12-02T15:05:04ZPolymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation10.1038/s41598-017-05232-02045-2322https://doaj.org/article/52abb5ec19ee44a2bc3a37aaeb8398252017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05232-0https://doaj.org/toc/2045-2322Abstract Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitochondrial dynamics and associated signaling in microglia are still poorly understood. In the present study, by combining immunohistochemistry and 3D ultrastructural analyses, we show that mitochondrial fission/fusion in reactive microglia is differentially regulated from that in monocyte-derived macrophages and the ramified microglia of normal white matter in myelin disease models. Mouse cerebral microglia in vitro demonstrated that stimulation of TLR4 with lipopolysaccharide, widely used to examine microglial reactions, caused the activation of the mitochondrial fission protein, dynamin-related protein 1 (Drp1) and enhanced production of reactive oxygen species (ROS). The increase in the ROS level activated 5′ adenosine monophosphate-activated protein kinase (AMPK), and facilitated elongation of mitochondria along the microtubule tracks. These results suggest that the polymorphic regulation of mitochondrial fission and fusion in reactive microglia is mediated by distinct signaling under inflammatory conditions, and modulates microglial phenotypes through the production of ROS.Mitsuhiko KatohBao WuHuy Bang NguyenTruc Quynh ThaiRyo YamasakiHaiyan LuAnna M. RietschMusab M. ZorluYouichi ShinozakiYurika SaitohSei SaitohTakashi SakohKazuhiro IkenakaSchuichi KoizumiRichard M. RansohoffNobuhiko OhnoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mitsuhiko Katoh Bao Wu Huy Bang Nguyen Truc Quynh Thai Ryo Yamasaki Haiyan Lu Anna M. Rietsch Musab M. Zorlu Youichi Shinozaki Yurika Saitoh Sei Saitoh Takashi Sakoh Kazuhiro Ikenaka Schuichi Koizumi Richard M. Ransohoff Nobuhiko Ohno Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation
description	Abstract Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitochondrial dynamics and associated signaling in microglia are still poorly understood. In the present study, by combining immunohistochemistry and 3D ultrastructural analyses, we show that mitochondrial fission/fusion in reactive microglia is differentially regulated from that in monocyte-derived macrophages and the ramified microglia of normal white matter in myelin disease models. Mouse cerebral microglia in vitro demonstrated that stimulation of TLR4 with lipopolysaccharide, widely used to examine microglial reactions, caused the activation of the mitochondrial fission protein, dynamin-related protein 1 (Drp1) and enhanced production of reactive oxygen species (ROS). The increase in the ROS level activated 5′ adenosine monophosphate-activated protein kinase (AMPK), and facilitated elongation of mitochondria along the microtubule tracks. These results suggest that the polymorphic regulation of mitochondrial fission and fusion in reactive microglia is mediated by distinct signaling under inflammatory conditions, and modulates microglial phenotypes through the production of ROS.
format	article
author	Mitsuhiko Katoh Bao Wu Huy Bang Nguyen Truc Quynh Thai Ryo Yamasaki Haiyan Lu Anna M. Rietsch Musab M. Zorlu Youichi Shinozaki Yurika Saitoh Sei Saitoh Takashi Sakoh Kazuhiro Ikenaka Schuichi Koizumi Richard M. Ransohoff Nobuhiko Ohno
author_facet	Mitsuhiko Katoh Bao Wu Huy Bang Nguyen Truc Quynh Thai Ryo Yamasaki Haiyan Lu Anna M. Rietsch Musab M. Zorlu Youichi Shinozaki Yurika Saitoh Sei Saitoh Takashi Sakoh Kazuhiro Ikenaka Schuichi Koizumi Richard M. Ransohoff Nobuhiko Ohno
author_sort	Mitsuhiko Katoh
title	Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation
title_short	Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation
title_full	Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation
title_fullStr	Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation
title_full_unstemmed	Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation
title_sort	polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/52abb5ec19ee44a2bc3a37aaeb839825
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Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation

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