title: Embryonic Medaka Model of Microglia in the Developing CNS Allowing In Vivo Analysis of Their Spatiotemporal Recruitment in Response to Irradiation.
abstract: Radiation therapy (RT) is pivotal in the treatment of many central nervous system (CNS) pathologies; however, exposure to RT in children is associated with a higher risk of secondary CNS tumors. Although recent research interest has focused on the reparative and therapeutic role of microglia, their recruitment following RT has not been elucidated, especially in the developing CNS. Here, we investigated the spatiotemporal dynamics of microglia during tissue repair in the irradiated embryonic medaka brain by whole-mount in situ hybridization using a probe for Apolipoprotein E (ApoE), a marker for activated microglia in teleosts. Three-dimensional imaging of the distribution of ApoE-expressing microglia in the irradiated embryonic brain clearly showed that ApoE-expressing microglia were abundant only in the late phase of phagocytosis during tissue repair induced by irradiation, while few microglia expressed ApoE in the initial phase of phagocytosis. This strongly suggests that ApoE has a significant function in the late phase of phagocytosis by microglia in the medaka brain. In addition, the distribution of microglia in p53-deficient embryos at the late phase of phagocytosis was almost the same as in wild-type embryos, despite the low numbers of irradiation-induced apoptotic neurons, suggesting that constant numbers of activated microglia were recruited at the late phase of phagocytosis irrespective of the extent of neuronal injury. This medaka model of microglia demonstrated specific recruitment after irradiation in the developing CNS and could provide a useful potential therapeutic strategy to counteract the detrimental effects of RT.
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, Tokyo University, Bioscience Bldg., Kashiwa, Chiba, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Yasuda
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, Tokyo University, Bioscience Bldg., Kashiwa, Chiba, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Oda
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, Tokyo University, Bioscience Bldg., Kashiwa, Chiba, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hibi
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, Tokyo University, Bioscience Bldg., Kashiwa, Chiba, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Satoh
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, Tokyo University, Bioscience Bldg., Kashiwa, Chiba, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Nagata
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, Tokyo University, Bioscience Bldg., Kashiwa, Chiba, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Hirakawa
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, Tokyo University, Bioscience Bldg., Kashiwa, Chiba, Japan.
authors.forename: Natsumaro
authors.initials: N
authors.lastname: Kutsuna
authors.affiliation: Fine Morphological Analysis Group, Medical Proteomics Laboratory, Institute of Medical Science, Tokyo University, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sagara
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, Tokyo University, Bioscience Bldg., Kashiwa, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002490:Central Nervous System / Q000502:physiology* / Q000528:radiation effects; D017628:Microglia / Q000502:physiology*; D009990:Oryzias / Q000196:embryology*; D011839:Radiation, Ionizing