EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany.
Dev Cell. 2012 Jun 12;22(6):1138-48. doi: 10.1016/j.devcel.2012.04.012. Epub 2012 May 24.
Microglia are the resident phagocytes of the brain that are responsible for the clearance of injured neurons, an essential step in subsequent tissue regeneration. How death signals are controlled both in space and time to attract these cells toward the site of injury is a topic of great interest. To this aim, we have used the optically transparent zebrafish larval brain and identified rapidly propagating Ca2+ waves that determine the range of microglial responses to neuronal cell death. We show that while Ca2+-mediated microglial responses require ATP, the spreading of intercellular Ca2+ waves is ATP independent. Finally, we identify glutamate as a potent inducer of Ca2+-transmitted microglial attraction. Thus, this real-time analysis reveals the existence of a mechanism controlling microglial targeted migration to neuronal injuries that is initiated by glutamate and proceeds across the brain in the form of a Ca2+ wave.
小胶质细胞是大脑中的固有吞噬细胞，负责清除受损神经元，这是随后组织再生的重要步骤。死亡信号如何在空间和时间上被控制，以吸引这些细胞向损伤部位移动，这是一个非常感兴趣的话题。为此，我们使用了光学透明的斑马鱼幼虫大脑，并确定了快速传播的 Ca2+波，这些波决定了小胶质细胞对神经元细胞死亡的反应范围。我们表明，虽然 Ca2+介导的小胶质细胞反应需要 ATP，但细胞间 Ca2+波的传播是不依赖于 ATP 的。最后，我们确定谷氨酸是一种强烈诱导 Ca2+传递的小胶质细胞吸引物。因此，这种实时分析揭示了一种控制小胶质细胞靶向迁移到神经元损伤的机制的存在，这种机制是由谷氨酸引发的，并以 Ca2+波的形式在大脑中传播。
