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Abscopal Activation of Microglia in Embryonic Fish Brain Following Targeted Irradiation with Heavy-Ion Microbeam

机译:重离子微束定向照射后胚胎鱼脑小胶质细胞的原始活化

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摘要

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 (Oryzias latipes), 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.
机译:当脊椎动物的中枢神经系统受到损伤时,小胶质细胞通过吞噬作用去除凋亡细胞。电离辐射(IR)诱导青aka(Oryzias latipes)胚胎中脑的凋亡和小胶质细胞活化,其中载脂蛋白E(ApoE)在小胶质细胞活化的后期被上调。在这项研究中,我们发现了另一种小胶质细胞标记物l-plastin当活化的小胶质细胞改变其形态并增加迁移的动力时,在淋巴细胞诱导的吞噬作用的初始阶段(淋巴细胞胞浆蛋白1)被上调。我们进一步使用准直的碳离子微束(直径250μm)对胚胎中脑进行了定向照射,发现仅在位于照射区域的小胶质细胞中诱导了l-增塑素的上调。然后,活化的小胶质细胞可能会迁移到被照射的区域外,并在整个胚胎脑中扩散,表达ApoE并具有活化的形态,照射后的时间超过3天。这些发现表明,l-plastin和ApoE可能分别是在medaka胚胎脑中处于初始阶段和后期的激活的小胶质细胞的生物标志物,而IR辐射引起的小胶质细胞的持续性和持续性活化可能是导致其继发性的和/或辐射后的不良影响。

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