中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (4): 705-716.doi: 10.4103/1673-5374.322423

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

小胶质细胞对突触可塑性和学习记忆的调节

  

  • 出版日期:2022-04-15 发布日期:2021-10-16

Microglia regulation of synaptic plasticity and learning and memory

Jessica Cornell#, Shelbi Salinas#, Hou-Yuan Huang#, Miou Zhou*   

  1. Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA
  • Online:2022-04-15 Published:2021-10-16
  • Contact: Miou Zhou, PhD, mzhou@westernu.edu.

摘要: Neural Regen Res: 静息小胶质细胞在突触可塑性和学习记忆中的作用
小胶质细胞是中枢神经系统的常驻巨噬细胞。在正常生理条件下,小胶质细胞主要以静息状态存在。静息小胶质细胞通过介导突触剪断,在视皮层和桶状皮层可塑性的调节中起重要作用,在学习记忆的调节中也起重要作用,包括对记忆强度、健忘和记忆质量的调节。作为对脑损伤、感染或神经炎症的反应,小胶质细胞被激活,数量增加。活化的小胶质细胞变为变形虫状,迁移到炎症部位,分泌细胞因子、趋化因子和活性氧等蛋白质。这些由小胶质细胞释放的分子可导致突触可塑性和学习记忆功能障碍,这些障碍与衰老、阿尔茨海默病、创伤性脑损伤、神经认知障碍以及其他精神障碍如自闭症、抑郁症和创伤后应激障碍有关。最新研究表明突触剪除是发育过程中精确的神经回路以及成人大脑中通过C1q、C3和CR3补体信号或CD47和信号调节蛋白的突触可塑性所必需的信号通路。静息小胶质细胞在调节神经元活动、突触传递以及突触结构的形成、修饰或消除方面具有重要的生理功能。小胶质细胞经常与神经元相互作用。通过脑源性神经营养因子和转化生长因子,小胶质细胞能够与神经元沟通以调节神经元功能。这种小胶质细胞神经元的交流不仅对大脑发育和成熟至关重要,而且对成熟大脑的突触可塑性和学习记忆也至关重要。
 来自美国西方卫生科学大学的Miou Zhou团队认为,由于小胶质细胞在突触修剪、突触可塑性和学习记忆中的重要作用,小胶质细胞的异常激活和由此引起的神经炎症已被证明是与正常衰老和不同疾病相关的认知缺陷的主要病因机制。小胶质细胞不仅是大脑的免疫和神经支持细胞,而且是突触结构和记忆强度与精确度的重要调节器,同时也是治疗认知障碍伴衰老、阿尔茨海默症等疾病的重要靶点。目前有许多成熟的小胶质细胞研究工具和技术,包括小胶质细胞诱导的CX3Cr1受体小鼠,小胶质细胞消除或抑制药物如氯膦酸盐,研究小胶质细胞特异性信号的单细胞或单核RNA测序,小胶质细胞标记,如Cx3cr1 GFP小鼠和双光子成像。除了目前可用的工具外,开发一种更有效、更方便的病毒工具,使小胶质细胞特异性感染和表达,将利于小胶质细胞研究的发展。
文章在《中国神经再生研究(英文版)》杂志2022年 4月 4 期发表。


https://orcid.org/0000-0001-8188-7392 (Miou Zhou)

Abstract: Microglia are the resident macrophages of the central nervous system. Microglia possess varied morphologies and functions. Under normal physiological conditions, microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity. Through the C1q, C3 and CR3 “Eat Me” and CD47 and SIRPα “Don’t Eat Me” complement pathways, as well as other pathways such as CX3CR1 signaling, resting microglia regulate synaptic pruning, a process crucial for the promotion of synapse formation and the regulation of neuronal activity and synaptic plasticity. By mediating synaptic pruning, resting microglia play an important role in the regulation of experience-dependent plasticity in the barrel cortex and visual cortex after whisker removal or monocular deprivation, and also in the regulation of learning and memory, including the modulation of memory strength, forgetfulness, and memory quality. As a response to brain injury, infection or neuroinflammation, microglia become activated and increase in number. Activated microglia change to an amoeboid shape, migrate to sites of inflammation and secrete proteins such as cytokines, chemokines and reactive oxygen species. These molecules released by microglia can lead to synaptic plasticity and learning and memory deficits associated with aging, Alzheimer’s disease, traumatic brain injury, HIV-associated neurocognitive disorder, and other neurological or mental disorders such as autism, depression and post-traumatic stress disorder. With a focus mainly on recently published literature, here we reviewed the studies investigating the role of resting microglia in synaptic plasticity and learning and memory, as well as how activated microglia modulate disease-related plasticity and learning and memory deficits. By summarizing the function of microglia in these processes, we aim to provide an overview of microglia regulation of synaptic plasticity and learning and memory, and to discuss the possibility of microglia manipulation as a therapeutic to ameliorate cognitive deficits associated with aging, Alzheimer’s disease, traumatic brain injury, HIV-associated neurocognitive disorder, and mental disorders.

Key words: aging, Alzheimer’s disease, cognitive deficits, experience-dependent plasticity, learning and memory, mental disorders, microglia, synaptic plasticity, synaptic pruning