Liu Ruo-Xu, Ma Jie, Guo Ning, Liu Shao-Jun
State Key Laboratory of Proteomics and Department of Neurobiology, Institute of Military Cognition and Brain Sciences, Beijing, China.
Neural Regen Res. 2020 Sep;15(9):1709-1715. doi: 10.4103/1673-5374.276342.
Microglia, as the resident immune cells in the central nervous system, play important roles in regulating neuronal processes, such as neural excitability, synaptic activity, and apoptotic cell clearance. Growth factors can activate multiple signaling pathways in central nervous system microglia and can regulate their immune effects, but whether growth factors can affect the morphological characteristics and ultrastructure of microglia has not been reported. After microinjecting 300 nL of a growth factor cocktail, including 10 μg/mL epidermal growth factor, 10 μg/mL basic fibroblast growth factor, 10 μg/mL hepatocyte growth factor and 10 μg/mL insulin-like growth factor into adult rat cortex, we found that the number of IBA1-positive microglia around the injection area increased significantly, indicating local activation of microglia. All CD68-positive labeling co-localized with IBA1 in microglia. Cell bodies and protrusions of CD68-positive cells were strongly attached to or were engulfing neurons. Characteristic huge phagosomes were observed in activated phagocytes by electron microscopy. The phagosomes generally included non-degraded neuronal protrusions and mitochondria, yet they contained no myelin membrane or remnants, which might indicate selective phagocytosis by the phagocytes. The remnant myelin sheath after phagocytosis still had regenerative ability and formed "myelin-like" structures around phagocytes. These results show that microinjection of a growth factor cocktail into the cerebral cortex of rodents can locally activate microglia and induce selective phagocytosis of neural structures by phagocytes. The study was approved by the Institute of Laboratory Animal Science, Beijing Institute of Basic Medical Sciences (approval No. IACUC-AMMS-2014-501) on June 30, 2014.
小胶质细胞作为中枢神经系统中的常驻免疫细胞，在调节神经元活动过程中发挥着重要作用，如神经兴奋性、突触活动和凋亡细胞清除。生长因子可激活中枢神经系统小胶质细胞中的多种信号通路，并调节其免疫效应，但生长因子是否会影响小胶质细胞的形态特征和超微结构尚未见报道。向成年大鼠皮层微量注射300 nL包含10 μg/mL表皮生长因子、10 μg/mL碱性成纤维细胞生长因子、10 μg/mL肝细胞生长因子和10 μg/mL胰岛素样生长因子的生长因子混合物后，我们发现注射区域周围IBA1阳性小胶质细胞数量显著增加，表明小胶质细胞发生了局部激活。小胶质细胞中所有CD68阳性标记均与IBA1共定位。CD68阳性细胞的胞体和突起与神经元紧密附着或正在吞噬神经元。通过电子显微镜在活化吞噬细胞中观察到特征性的巨大吞噬体。吞噬体通常包含未降解的神经元突起和线粒体，但不包含髓鞘膜或残余物，这可能表明吞噬细胞进行了选择性吞噬。吞噬后残留的髓鞘仍具有再生能力，并在吞噬细胞周围形成“髓鞘样”结构。这些结果表明，向啮齿动物大脑皮层微量注射生长因子混合物可局部激活小胶质细胞，并诱导吞噬细胞对神经结构进行选择性吞噬。该研究于2014年6月30日获得北京基础医学研究所实验动物科学研究所批准（批准号：IACUC - AMMS - 2014 - 501）。
