中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (6): 1019-1025.doi: 10.4103/1673-5374.233445

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

小脑浦肯野细胞突触老化导致突触形态和功能紊乱

  

  • 收稿日期:2017-12-15 出版日期:2018-06-15 发布日期:2018-06-15
  • 基金资助:

    河南省科技项目(172102310001)和河南省生物优势学科基金资助

Synaptic aging disrupts synaptic morphology and function in cerebellar Purkinje cells

Wen-Juan Fan, Ming-Chao Yan, Lai Wang, Yi-Zheng Sun, Jin-Bo Deng, Jie-Xin Deng   

  1. Institute of Neurobiology, School of Life Science, Henan University, Kaifeng, Henan Province, China
  • Received:2017-12-15 Online:2018-06-15 Published:2018-06-15
  • Contact: Lai Wang or Jin-Bo Deng,wanglai@ henu.edu.cn or jinbo_deng@henu.edu.cn.
  • Supported by:

    This study was supported by the Science and Technology Projects of Henan Province of China, No. 172102310001; the Biology Advantage Discipline Fund of Henan Province of China.

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摘要：

突触是参与神经网络形成的关键结构，与中枢神经系统学习与记忆功能关系密切。研究突触发生和突触老化对于了解神经发育和神经退行性如阿尔茨海默病和帕金森病的发病机制具有重要意义。课题组以往研究发现突触的发生与成熟与大脑功能发育的完善相一致，但对小脑衰老过程中突触的发生与损伤之间的关系还不十分清楚。为此，实验设计观察小鼠小脑浦肯野细胞树突棘和突触超微结构的变化，探讨小脑突触衰老的发生。利用不同年龄段出生的小鼠，通过免疫细胞化学、DiI散射以及透射电子显微镜技术观察小脑浦肯野细胞中突触扣、树突棘以及突触的形态特征，发现随着浦肯野细胞突触老化的发生，树突棘和突触扣在小脑中逐渐消失，突触超微结构也发生改变，如突触前末梢突触囊泡和线粒体在减少，突触前膜和突触后膜的特异性区域也在减少。上述数据说明，小脑浦肯野细胞突触老化导致的突触形态和功能紊乱，可能是发生神经退行性疾病的重要病理原因。

orcid:0000-0002-3323-7210(Lai Wang)
        0000-0002-4618-2300(Jin-Bo Deng)

关键词: 衰老, 小脑, 树突棘, 退行性疾病, 小鼠, 浦肯野细胞, 突触, 突触发生, 突触超微结构, 神经退行性病, 神经再生

Abstract:

Synapses are key structures in neural networks, and are involved in learning and memory in the central nervous system. Investigating synaptogenesis and synaptic aging is important in understanding neural development and neural degeneration in diseases such as Alzheimer disease and Parkinson’s disease. Our previous study found that synaptogenesis and synaptic maturation were harmonized with brain development and maturation. However, synaptic damage and loss in the aging cerebellum are not well understood. This study was designed to investigate the occurrence of synaptic aging in the cerebellum by observing the ultrastructural changes of dendritic spines and synapses in cerebellar Purkinje cells of aging mice. Immunocytochemistry, DiI diolistic assays, and transmission electron microscopy were used to visualize the morphological characteristics of synaptic buttons, dendritic spines and synapses of Purkinje cells in mice at various ages.With synaptic aging in the cerebellum, dendritic spines and synaptic buttons were lost, and the synaptic ultrastructure was altered, including a reduction in the number of synaptic vesicles and mitochondria in presynaptic termini and smaller thin specialized zones in pre- and post-synaptic membranes. These findings confirm that synaptic morphology and function is disrupted in aging synapses, which may be an important pathological cause of neurodegenerative diseases.

Key words: nerve regeneration, aging, cerebellum, degenerative disease, dendritic spine, nerve regeneration, mice, neurodegenerative diseases, Purkinje cells, synapse, synaptogenesis, synaptic ultrastructure, neural regeneration