实用医学杂志 ›› 2022, Vol. 38 ›› Issue (20): 2624-2629.doi: 10.3969/j.issn.1006⁃5725.2022.20.021

• 综述 • 上一篇    下一篇

小胶质细胞介导的突触修剪在慢性脑缺血中的作用及其机制 

汤诗怡 赖梅菁 邱美茜 詹丽璇    

  1. 广州医科大学附属第二医院神经内科,广州医科大学神经科学研究所(广州 510260)

  • 出版日期:2022-10-25 发布日期:2022-10-25
  • 通讯作者: 詹丽璇 E⁃mail:xuan060912@163.com
  • 基金资助:
    国家自然科学基金面上项目(编号:81971124;82271330);广州市医学重点学科建设项目(编号:2021⁃2023)

The role and mechanism of microglia⁃mediated synaptic pruning in chronic cerebral ischemia

TANG ShiyiLAI MeijingQIU MeiqianZHAN Lixuan.   

  1. Institute of Neurosciencesthe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China

  • Online:2022-10-25 Published:2022-10-25
  • Contact: ZHAN Lixuan E⁃mail:xuan060912@163.com

摘要:

慢性脑缺血又称慢性脑低灌注,是造成以脑白质损伤和认知功能减退为主要表现的多种中 枢神经系统疾病的重要原因。已有研究表明,持续性慢性脑缺血会引起小胶质细胞的异常激活,导致髓鞘 再生障碍和突触过度丢失。在正常的神经系统发育过程中,小胶质细胞可通过补体 3/补体 1q/补体受体 3 complement 3/complement 1q/complement receptor 3C3/C1q/CR3)和趋化因子 C⁃X3⁃C⁃基序配体 1/C⁃X3⁃C⁃基 序受体 1C⁃X3⁃C motif chemokine ligand 1/C⁃X3⁃C motif chemokine receptor 1CX3CL1/CX3CR1)信号通路等 多种分子机制吞噬多余的突触,介导突触修剪。然而,在包括慢性脑缺血在内的多种中枢神经系统疾病 中,调控突触修剪的这些分子机制异常,引起小胶质细胞吞噬功能受损或过度激活,导致突触异常堆积或 丢失,最终引起认知功能障碍。本文综述了小胶质细胞在慢性脑缺血后介导的突触异常修剪的相关分子 机制,为治疗慢性脑缺血所致的认知功能障碍寻找潜在的靶点。

关键词:

慢性脑缺血, 小胶质细胞, 星形胶质细胞, 突触修剪, 吞噬

Abstract:

Chronic cerebral ischemiaalso known as chronic cerebral hypoperfusionis a major cause of various central nervous system diseases with main manifestations of white matter injury and cognitive decline. Per⁃ sistent cerebral hypoperfusion has been shown to induce abnormal activation of microgliaresulting in impairment of myelin regeneration and excessive loss of synapses. During brain developmentmicroglia can associate with multiple molecular mechanismssuch ascomplement 3/complement 1q/complement receptor 3C3/C1q/CR3or the C⁃X3⁃C motif chemokine ligand 1/C⁃X3⁃C motif chemokine receptor 1CX3CL1/ CX3CR1signaling pathway to engulf the redundantsynapses and mediate synaptic elimination. Howeveramong a variety of central nervous system diseases including chronic cerebral ischemiathe abnormalities of the above molecular mechanisms often lead to the altered microglial phagocytosiswhich ultimately results inaccumulation or loss of synapses and cogni⁃ tive dysfunction. This paper reviews the researches intothe roles and mechanisms of microglia ⁃ mediated synaptic elimination after chronic cerebral ischemia so as to look for a potential target for treating cognitive declines induced by chronic cerebral ischemia. 

Key words:

chronic cerebral ischemia, microglia, astrocyte, synaptic pruning, phagocytosis