Neural Regeneration Research ›› 2014, Vol. 9 ›› Issue (19): 1731-1739.doi: 10.4103/1673-5374.143415

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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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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