中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (19): 1731-1739.doi: 10.4103/1673-5374.143415

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

长期给予东茛菪碱成年小鼠海马齿状回神经细胞无死亡但增殖、分化和迁移行为被破坏

  

  • 收稿日期:2014-09-04 出版日期:2014-10-15 发布日期:2014-10-15
  • 基金资助:

    韩国教育科技部国家研究项目

Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death

Bing Chun Yan 1, Joon Ha Park 2, Bai Hui Chen 3, Jeong-Hwi Cho 2, In Hye Kim 2, Ji Hyeon Ahn 2, Jae-Chul Lee 2, In Koo Hwang 4, Jun Hwi Cho 5, Yun Lyul Lee 3, Il-Jun Kang 6, Moo-Ho Won 2   

  1. 1 Department of Integrative Traditional & Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
    2 Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea
    3 Department of Physiology, College of Medicine, Institute of Neurodegeneration and Neuroregeneration, Hallym University, Chuncheon, South Korea
    4 Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea
    5 Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, South Korea
    6 Department of Food Science and Nutrition, Hallym University, Chuncheon, South Korea
  • Received:2014-09-04 Online:2014-10-15 Published:2014-10-15
  • Contact: Moo-Ho Won, D.V.M., Ph.D., Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea, mhwon@kangwon.ac.kr. Il-Jun Kang, Ph.D., Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, South Korea, ijkang@hallym.ac.kr.
  • Supported by:
    This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, No. 2010-0010580, and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning, No. NRF-2013R1A2A2A01068190.
     

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摘要：

长期给予毒蕈碱受体拮抗剂东茛菪碱可抑制大脑新生细胞的存活，但其对成年小鼠海马齿状回神经细胞增殖、分化、迁移的影响尚不清楚，实验拟明确这一机制。给予成年小鼠腹腔注射东茛菪碱4周，应用免疫组化和免疫印迹法每周检测海马齿状回神经细胞生物学行为。检测神经元标志物NeuN和神经元退变标志物Fluoro-Jade B发现，东茛菪碱干预小鼠海马齿状回无神经元死亡，细胞增殖标志物Ki-67免疫阳性细胞数量随时间明显减少，4周达到最低。新生神经元标志物DCX免疫阳性细胞的突起随时间逐渐变短、变少。东茛菪碱干预4周后，BrdU标记的新生细胞几乎均定位于齿状回颗粒细胞下层，而未迁移至颗粒细胞层；齿状回几乎未见BrdU/NeuN免疫荧光双标阳性成熟神经元。说明长期东茛菪碱干预可破坏成年小鼠海马齿状回细胞增殖、分化和迁移行为，但并不会使成年神经元发生死亡。

关键词: 神经再生, 神经发生, 东茛菪碱, 齿状回, 细胞增殖, 细胞分化, 细胞迁移, 颗粒细胞层

Abstract:

Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperitoneal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN; a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reached the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-immunoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2′-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These findings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death.

Key words: nerve regeneration, neurogenesis, scopolamine, dentate gyrus, cell proliferation, neuroblast differentiation, neuroblast migration, granule cell layer, neural regeneration