Xie Meizhen, Wang Tian, Feng Jiachun, Ma Di, Feng Liangshu, Hao Yulei
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, The Netherlands.
The Second Hospital of Jilin University, Changchun, Jilin Province 130021, People's Republic of China.
Curr Neuropharmacol. 2025 Feb 26. doi: 10.2174/1570159X23666250225091729.
Microglia are resident immune cells in the brain that have been widely studied for their immune surveillance and phagocytosis. In recent years, the important role of microglia in synapse formation, elimination, and plasticity is gradually being recognized. Synapses are the main communication mode between neurons. They undergo constant changes in quantity and plasticity throughout the life cycle, which is the basis of learning and memory. Microglia are highly motile, branched forms that monitor the microenvironment of the central nervous system (CNS) and promote synapse formation and maturation. They recognize and phagocytose redundant synapses through specific phagocytosis receptors. Furthermore, microglia regulate synaptic plasticity by releasing various effectors. The roles of microglia on synapses ensure the proper function of neural networks. Synaptic dysfunction and microglia activation are common features in CNS disorders, such as Alzheimer's disease, Parkinson's disease, ischemic stroke, cerebral hemorrhage, traumatic brain injury, multiple sclerosis, and epilepsy. Highly heterogeneous microglia exhibit diverse functions in these diseases and participate in disease progression by exacerbating or inhibiting synaptic dysfunction, in addition to neuroimmune and inflammation. In this article, we summarize the role of microglia on synapses under physiological conditions and in CNS disorders. We highlight the possible mechanisms by which microglia regulate synapse function in CNS disorders and how this affects the progression of the diseases. We aim to explore potential therapeutic targets for CNS disorders.
小胶质细胞是大脑中的常驻免疫细胞，因其免疫监视和吞噬作用而受到广泛研究。近年来，小胶质细胞在突触形成、消除和可塑性方面的重要作用逐渐得到认可。突触是神经元之间主要的通讯方式。它们在整个生命周期中数量和可塑性不断变化，这是学习和记忆的基础。小胶质细胞具有高度的运动性，呈分支状，监测中枢神经系统（CNS）的微环境并促进突触形成和成熟。它们通过特定的吞噬受体识别并吞噬多余的突触。此外，小胶质细胞通过释放各种效应物来调节突触可塑性。小胶质细胞在突触上的作用确保了神经网络的正常功能。突触功能障碍和小胶质细胞激活是中枢神经系统疾病的常见特征，如阿尔茨海默病、帕金森病、缺血性中风、脑出血、创伤性脑损伤、多发性硬化症和癫痫。高度异质性的小胶质细胞在这些疾病中表现出多种功能，除了神经免疫和炎症外，还通过加剧或抑制突触功能障碍参与疾病进展。在本文中，我们总结了小胶质细胞在生理条件下和中枢神经系统疾病中对突触的作用。我们强调了小胶质细胞在中枢神经系统疾病中调节突触功能的可能机制以及这如何影响疾病的进展。我们旨在探索中枢神经系统疾病的潜在治疗靶点。
