围神经元网、硫酸软骨素蛋白多糖受体及其对神经可塑性的调节作用
缪庆龙, 叶倩, 章晓辉
中国科学院上海生命科学研究院神经科学研究所;中国科学院大学,上海 200031;北京师范大学脑与认知神经科学研究院,认知神经科学与学习国家重点实验室,北京 100875
摘要
围神经元网是中枢神经系统中一种包绕在特定类型神经元胞体和近端神经突周围的细胞外基质网络。在1883年,围神经元网最早被Camillo Golgi所描述,直到近几十年,研究人员才对其分子组成、发育成熟以及潜在的功能有密集的研究。研究表明,围神经元网主要由透明质酸、硫酸软骨素蛋白多糖、连接蛋白和肌腱蛋白-R组成。围神经元网在神经发育的晚期才渐次出现,它的发育成熟水平和神经可塑性水平的高低呈负相关。功能上,一方面,围神经网络被认为在稳定细胞外微环境、维持被包裹神经元的性能和保护被包裹的神经元免受有害物质的影响等方面起到了重要的作用,围神经元网的异常可以导致诸如癫痫、中风和阿尔茨海默病等中枢神经系统的机能障碍;另一方面,围神经元网作为包裹在细胞外的一道屏障限制了神经可塑性的发生和阻碍了神经损伤后的再生。在成年动物中,用软骨素酶法降解围神经元网可以促进脊髓损伤后的功能修复以及恢复活动依赖的中枢神经系统可塑性调节机制,表明围神经元网在调节神经可塑性方面起到了非常重要的作用。本文就早期发育中活动依赖的围神经网络的形成和围神经网络信号通路中的重要分子——硫酸软骨素蛋白多糖受体的研究进展进行综述,并就它们如何调节神经可塑性展开讨论。
关键词: 围神经元网; 硫酸软骨素蛋白多糖受体; 突触; 硫酸软骨素酶ABC; 脊髓损伤; 神经可塑性
分类号:Q25
Perineuronal net, CSPG receptor and their regulation of neural plasticity
MIAO Qing-Long, YE Qian, ZHANG Xiao-Hui
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Shanghai 200031, China; School of Brain and Cognitive Sciences and State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China
Abstract
Perineuronal nets (PNNs) are reticular structures resulting from the aggregation of extracellular matrix (ECM) molecules around the cell body and proximal neurite of specific population of neurons in the central nervous system (CNS). Since the first description of PNNs by Camillo Golgi in 1883, the molecular composition, developmental formation and potential functions of these specialized extracellular matrix structures have only been intensively studied over the last few decades. The main components of PNNs are hyaluronan (HA), chondroitin sulfate proteoglycans (CSPGs) of the lectican family, link proteins and tenascin-R. PNNs appear late in neural development, inversely correlating with the level of neural plasticity. PNNs have long been hypothesized to play a role in stabilizing the extracellular milieu, which secures the characteristic features of enveloped neurons and protects them from the influence of malicious agents. Aberrant PNN signaling can lead to CNS dysfunctions like epilepsy, stroke and Alzheimer's disease. On the other hand, PNNs create a barrier which constrains the neural plasticity and counteracts the regeneration after nerve injury. Digestion of PNNs with chondroitinase ABC accelerates functional recovery from the spinal cord injury and restores activity-dependent mechanisms for modifying neuronal connections in the adult animals, indicating that PNN is an important regulator of neural plasticity. Here, we review recent progress in the studies on the formation of PNNs during early development and the identification of CSPG receptor - an essential molecular component of PNN signaling, along with a discussion on their unique regulatory roles in neural plasticity.
Key words: perineuronal net; CSPG receptor; synapse; chondroitinase ABC; spinal cord injury; neural plasticity
收稿日期:2013-12-12 录用日期:2014-02-13
通讯作者:缪庆龙 E-mail: qlmiao@ion.ac.cn
引用本文:
缪庆龙, 叶倩, 章晓辉. 围神经元网、硫酸软骨素蛋白多糖受体及其对神经可塑性的调节作用[J]. 生理学报 2014; 66 (4): 387-397.
MIAO Qing-Long, YE Qian, ZHANG Xiao-Hui. Perineuronal net, CSPG receptor and their regulation of neural plasticity. Acta Physiol Sin 2014; 66 (4): 387-397 (in Chinese with English abstract).