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“四联体”突触:发育和成熟中枢神经系统中的小胶质细胞-突触相互作用。

The "quad-partite" synapse: microglia-synapse interactions in the developing and mature CNS.

机构信息

Department of Neurology, F.M. Kirby Neurobiology Center, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Glia. 2013 Jan;61(1):24-36. doi: 10.1002/glia.22389. Epub 2012 Jul 24.

Abstract

Microglia are the resident immune cells and phagocytes of our central nervous system (CNS). While most work has focused on the rapid and robust responses of microglia during CNS disease and injury, emerging evidence suggests that these mysterious cells have important roles at CNS synapses in the healthy, intact CNS. Groundbreaking live imaging studies in the anesthetized, adult mouse demonstrated that microglia processes dynamically survey their environment and interact with other brain cells including neurons and astrocytes. More recent imaging studies have revealed that microglia dynamically interact with synapses where they appear to serve as "synaptic sensors," responding to changes in neural activity and neurotransmitter release. In the following review, we discuss the most recent work demonstrating that microglia play active roles at developing and mature synapses. We first discuss the important imaging studies that have led us to better understand the physical relationship between microglia and synapses in the healthy brain. Following this discussion, we review known molecular mechanisms and functional consequences of microglia-synapse interactions in the developing and mature CNS. Our current knowledge sheds new light on the critical functions of these mysterious cells in synapse development and function in the healthy CNS, but has also incited several new and interesting questions that remain to be explored. We discuss these open questions, and how the most recent findings in the healthy CNS may be related to pathologies associated with abnormal and/or loss of neural circuits.

摘要

小胶质细胞是我们中枢神经系统 (CNS) 的固有免疫细胞和吞噬细胞。虽然大多数研究都集中在中枢神经系统疾病和损伤中小胶质细胞的快速和强烈反应上,但新出现的证据表明,这些神秘的细胞在健康完整的中枢神经系统中的中枢神经系统突触中具有重要作用。在麻醉的成年小鼠中进行的开创性活体成像研究表明,小胶质细胞的突起能够动态地探测其周围环境,并与其他脑细胞(包括神经元和星形胶质细胞)相互作用。最近的成像研究表明,小胶质细胞与突触动态相互作用,在那里它们似乎充当“突触传感器”,对神经活动和神经递质释放的变化做出反应。在接下来的综述中,我们讨论了最近的研究工作,这些研究工作表明小胶质细胞在发育中和成熟的突触中发挥着积极的作用。我们首先讨论了一些重要的成像研究,这些研究使我们能够更好地理解健康大脑中小胶质细胞和突触之间的物理关系。在讨论之后,我们回顾了已知的分子机制和小胶质细胞-突触相互作用在发育中和成熟中枢神经系统中的功能后果。我们目前的知识为这些神秘细胞在健康中枢神经系统中突触发育和功能的关键作用提供了新的认识,但也引发了几个新的有趣问题,这些问题仍有待探索。我们讨论了这些悬而未决的问题,以及健康中枢神经系统中的最新发现与异常和/或丧失神经网络相关的病理学之间可能存在的关系。

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