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 (3): 427-433.doi: 10.4103/1673-5374.228724

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

中枢神经系统发育阶段轴突延伸和髓鞘形成所必需的原钙粘蛋白α

  

  • 收稿日期:2018-01-12 出版日期:2018-03-15 发布日期:2018-03-15
  • 基金资助:

    上海市科技委员会项目（12441900702）

The protocadherin alpha cluster is required for axon extension and myelination in the developing central nervous system

Wen-cheng Lu1, Yu-xiao Zhou2, Ping Qiao3, Jin Zheng2, Qiang Wu2, Qiang Shen1   

  1. 1 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    2 Center for Comparative Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Institute of Systems Biomedicine,Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
    3 Department of Orthopedics, People’s Hospital of Zhangqiu, Zhangqiu, Shandong Province, China
  • Received:2018-01-12 Online:2018-03-15 Published:2018-03-15
  • Contact: Qiang Wu, Ph.D. or Qiang Shen, M.D., Ph.D.,qwu123@gmail.com or shmail1231@yahoo.com.
  • Supported by:

    This study was supported by a grant from the Science and Technology Commission of Shanghai Municipality of China, No.12441900702.

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摘要：

成年哺乳动物中枢神经系统损伤后轴突再生的能力极差，会导致持续性功能丧失。由于成年中枢神经系统成熟神经元仍保留有轴突再生的能力，所以增强这种能力可能是一种可行的治疗策略，原钙粘蛋白被认为在神经元形态发生和大脑中神经回路正确组装中起重要作用。实验体外培养了E17.5d去除原钙粘蛋白α的转基因胎鼠的海马神经元，培养1d后发现神经元轴突长度明显比野生型小鼠短。紧接着，他们利用新一代测序技术RNA-SEQ，提取E17.5d胎鼠海马RNA进行了测序，发现敲除原钙粘蛋白α后，与神经元轴突生长特别是与轴突延伸相关的基因如 BDNF, Fmod, Nrp2, OGN和 Sema3d的表达显著下调。最后，他们将出生21d小鼠海马切片进行了电镜观察，发现敲除原钙粘蛋白α后小鼠海马神经元轴突有髓神经纤维比例明显下降，且髓鞘板层紊乱，不连续，有空泡出现。因此说明说明原钙粘蛋白α对神经发育阶段神经元轴突的生长与髓鞘化形成的促进作用。

orcid:0000-0002-7782-9963(Qiang Shen)

关键词: 神经再生, 脊髓损伤, 轴突, 原钙粘蛋白&alpha, 海马神经元, RNA测序, 实时定量PCR, 透射电镜

Abstract:

In adult mammals, axon regeneration after central nervous system injury is very poor, resulting in persistent functional loss. Enhancing the ability of axonal outgrowth may be a potential treatment strategy because mature neurons of the adult central nervous system may retain the intrinsic ability to regrow axons after injury. The protocadherin (Pcdh) clusters are thought to function in neuronal morphogenesis and in the assembly of neural circuitry in the brain. We cultured primary hippocampal neurons from E17.5 Pcdhα deletion (del-α) mouse embryos. After culture for 1 day, axon length was obviously shorter in del-α neurons compared with wild-type neurons. RNA sequencing of hippocampal E17.5 RNA showed that expression levels of BDNF, Fmod, Nrp2, OGN, and Sema3d, which are associated with axon extension, were significantly down-regulated in the absence of the Pcdhα gene cluster. Using transmission electron microscopy, the ratio of myelinated nerve fibers in the axons of del-α hippocampal neurons was significantly decreased; myelin sheaths of P21 Pcdhα-del mice showed lamellar disorder, discrete appearance, and vacuoles. These results indicate that the Pcdhα cluster can promote the growth and myelination of axons in the neurodevelopmental stage.

Key words: nerve regeneration, spinal cord injury, axons, protocadherin &alpha, cluster, hippocampal neurons, RNA sequencing, real-time quantitative polymerase chain reaction, transmission electron microscopy, neural regeneration