Embryonic Medaka Model of Microglia in the Developing CNS Allowing In Vivo Analysis of Their Spatiotemporal Recruitment in Response to Irradiation.
Embryonic Medaka Model of Microglia in the Developing CNS Allowing In Vivo Analysis of Their Spatiotemporal Recruitment in Response to Irradiation.
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DOI：
10.1371/journal.pone.0127325
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Mitani H
中科院分区：
文献类型：
--
作者：
Yasuda T;Oda S;Hibi Y;Satoh S;Nagata K;Hirakawa K;Kutsuna N;Sagara H;Mitani H
放射治疗(RT)在许多中枢神经系统(CNS)疾病的治疗中起着关键作用；然而，儿童暴露于RT与继发性中枢神经系统肿瘤的风险较高相关。虽然最近的研究兴趣主要集中在小胶质细胞的修复和治疗作用上，但它们在RT后的招募还没有被阐明，特别是在发育中的中枢神经系统。在这里，我们使用硬骨鱼中激活的小胶质细胞的标志物载脂蛋白E(ApoE)的探针，通过整体原位杂交研究了受辐射的胚胎青竹脑中小胶质细胞在组织修复过程中的时空动态。照射后胚胎脑内表达载脂蛋白E的小胶质细胞的三维成像显示，只有在组织修复过程中的吞噬后期才有大量表达载脂蛋白E的小胶质细胞，而在吞噬初期表达载脂蛋白E的小胶质细胞很少。这有力地表明，载脂蛋白E在青竹脑小胶质细胞吞噬的晚期有重要作用。此外，小胶质细胞在p53缺陷胚胎吞噬后期的分布几乎与野生型胚胎相同，尽管辐射诱导的凋亡神经元数量很少，这表明在吞噬后期，无论神经元损伤的程度如何，都会招募到恒定数量的激活的小胶质细胞。这种青竹小胶质细胞模型显示了照射后小胶质细胞在发育中的中枢神经系统中的特异性募集，并可能提供一种有用的潜在治疗策略来对抗RT的有害影响。
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.
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影响因子：
5.3
作者：
Miyamoto A;Wake H;Moorhouse AJ;Nabekura J
通讯作者：
Nabekura J
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
DOI：
10.1126/science.1217697
发表时间：
2012-03-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cramer PE;Cirrito JR;Wesson DW;Lee CY;Karlo JC;Zinn AE;Casali BT;Restivo JL;Goebel WD;James MJ;Brunden KR;Wilson DA;Landreth GE
通讯作者：
Landreth GE
影响因子：
1.7
作者：
Ishikawa, Yuji;Yamamoto, Naoyuki;Ito, Hironobu
通讯作者：
Ito, Hironobu
影响因子：
4.2
作者：
LEBLANC, AC;PODUSLO, JF
通讯作者：
PODUSLO, JF