National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, MD C1-04, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
Pharmacol Ther. 2013 Sep;139(3):313-26. doi: 10.1016/j.pharmthera.2013.04.013. Epub 2013 Apr 30.
Microglia are critical nervous system-specific cells influencing brain development, maintenance of the neural environment, response to injury, and repair. They contribute to neuronal proliferation and differentiation, pruning of dying neurons, synaptic remodeling and clearance of debris and aberrant proteins. Colonization of the brain occurs during gestation with an expansion following birth with localization stimulated by programmed neuronal death, synaptic pruning, and axonal degeneration. Changes in microglia phenotype relate to cellular processes including specific neurotransmitter, pattern recognition, or immune-related receptor activation. Upon activation, microglia cells have the capacity to release a number of substances, e.g., cytokines, chemokines, nitric oxide, and reactive oxygen species, which could be detrimental or beneficial to the surrounding cells. With aging, microglia shift their morphology and may display diminished capacity for normal functions related to migration, clearance, and the ability to shift from a pro-inflammatory to an anti-inflammatory state to regulate injury and repair. This shift in microglia potentially contributes to increased susceptibility and neurodegeneration as a function of age. In the current review, information is provided on the colonization of the brain by microglia, the expression of various pattern recognition receptors to regulate migration and phagocytosis, and the shift in related functions that occur in normal aging.
小胶质细胞是神经系统特有的关键细胞，影响大脑发育、神经环境的维持、对损伤的反应和修复。它们促进神经元的增殖和分化、死亡神经元的修剪、突触重塑以及清除碎片和异常蛋白。脑的定植发生在妊娠期，出生后随着程序性神经元死亡、突触修剪和轴突退化而扩张。小胶质细胞表型的变化与细胞过程有关，包括特定的神经递质、模式识别或免疫相关受体的激活。小胶质细胞被激活后，具有释放多种物质的能力，例如细胞因子、趋化因子、一氧化氮和活性氧，这些物质可能对周围细胞有害或有益。随着年龄的增长，小胶质细胞改变其形态，可能表现出迁移、清除和从炎症前状态向抗炎状态转变以调节损伤和修复的正常功能的能力减弱。小胶质细胞的这种转变可能导致年龄相关的易感性和神经退行性变增加。在目前的综述中，提供了关于小胶质细胞在大脑中的定植、各种模式识别受体表达以调节迁移和吞噬作用以及正常衰老过程中相关功能的转变的信息。
