Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Curr Opin Neurobiol. 2023 Aug;81:102732. doi: 10.1016/j.conb.2023.102732. Epub 2023 May 27.
In the central nervous system, synaptic pruning, the removal of unnecessary synaptic contacts, is an essential process for proper circuit maturation in neurodevelopment as well as for synaptic homeostasis in the adult stage. Dysregulation of synaptic pruning can contribute to the initiation and progression of various mental disorders, such as schizophrenia and depression, as well as neurodegenerative diseases including Alzheimer's disease. In the past 15 years, pioneering works have demonstrated that different types of glial cells regulate the number of synapses by selectively eliminating them through phagocytic molecular machinery. Although a majority of findings have been focused on microglia, it is increasingly evident that astrocytes function as a critical player in activity-dependent synapse elimination in developing, adult, and diseased brains. In this review, we will discuss recent findings showing the mechanisms and physiological importance of astrocyte-mediated synapse elimination in controlling synapses and circuit homeostasis. We propose that astrocytes play dominant and non-redundant roles in eliminating synapses during the activity-dependent circuit remodeling processes that do not involve neuro-inflammation.
在中枢神经系统中，突触修剪（即去除不必要的突触连接）是神经发育过程中正确的回路成熟以及成年阶段突触稳态的必要过程。突触修剪的失调可能导致各种精神障碍（如精神分裂症和抑郁症）以及神经退行性疾病（包括阿尔茨海默病）的发生和发展。在过去的 15 年中，开创性的研究工作表明，不同类型的神经胶质细胞通过吞噬分子机制有选择地消除突触来调节突触的数量。尽管大多数研究结果都集中在小胶质细胞上，但越来越明显的是，星形胶质细胞在发育、成年和患病大脑中活动依赖性突触消除中起着关键作用。在这篇综述中，我们将讨论最近的发现，这些发现表明星形胶质细胞介导的突触消除的机制和生理重要性，以控制突触和回路稳态。我们提出，星形胶质细胞在不涉及神经炎症的活动依赖性回路重塑过程中，发挥着消除突触的主导和非冗余作用。
