Yasuda Takako, Kamahori Miyuki, Nagata Kento, Watanabe-Asaka Tomomi, Suzuki Michiyo, Funayama Tomoo, Mitani Hiroshi, Oda Shoji
Department of Integrated Biosciences, Graduated School of Frontier Sciences, The University of Tokyo, Kashiwa, 277-8562 Chiba, Japan.
Takasaki Advanced Radiation Research Institute, Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology, 370-1292 Gunma, Japan.
Int J Mol Sci. 2017 Jul 4;18(7):1428. doi: 10.3390/ijms18071428.
Microglia remove apoptotic cells by phagocytosis when the central nervous system is injured in vertebrates. Ionizing irradiation (IR) induces apoptosis and microglial activation in embryonic midbrain of medaka (), where apolipoprotein E (ApoE) is upregulated in the later phase of activation of microglia In this study, we found that another microglial marker, l-plastin (lymphocyte cytosolic protein 1), was upregulated at the initial phase of the IR-induced phagocytosis when activated microglia changed their morphology and increased motility to migrate. We further conducted targeted irradiation to the embryonic midbrain using a collimated microbeam of carbon ions (250 μm diameter) and found that the l-plastin upregulation was induced only in the microglia located in the irradiated area. Then, the activated microglia might migrate outside of the irradiated area and spread through over the embryonic brain, expressing ApoE and with activated morphology, for longer than 3 days after the irradiation. These findings suggest that l-plastin and ApoE can be the biomarkers of the activated microglia in the initial and later phase, respectively, in the medaka embryonic brain and that the abscopal and persisted activation of microglia by IR irradiation could be a cause of the abscopal and/or adverse effects following irradiation.
在脊椎动物中，当中枢神经系统受损时，小胶质细胞通过吞噬作用清除凋亡细胞。电离辐射（IR）可诱导青鳉胚胎中脑发生凋亡和小胶质细胞活化，在小胶质细胞活化后期，载脂蛋白E（ApoE）上调。在本研究中，我们发现另一种小胶质细胞标志物l-原肌球蛋白（淋巴细胞胞质蛋白1）在IR诱导的吞噬作用初始阶段上调，此时活化的小胶质细胞改变形态并增加迁移运动性。我们进一步使用直径250μm的碳离子准直微束对胚胎中脑进行靶向照射，发现仅在照射区域内的小胶质细胞中诱导了l-原肌球蛋白上调。然后，活化的小胶质细胞可能迁移到照射区域之外并扩散到整个胚胎脑，在照射后3天以上表达ApoE并呈现活化形态。这些发现表明，l-原肌球蛋白和ApoE可分别作为青鳉胚胎脑中活化小胶质细胞初始阶段和后期阶段的生物标志物，并且IR照射引起的小胶质细胞远隔和持续活化可能是照射后远隔效应和/或不良反应的一个原因。
