title: 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.
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.
authors.affiliation: Department of Integrative Traditional & Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China.
authors.forename: Bing Chun
authors.initials: BC
authors.lastname: Yan
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Physiology, College of Medicine, Institute of Neurodegeneration and Neuroregeneration, Hallym University, Chuncheon, South Korea.
authors.forename: Bai Hui
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea.
authors.forename: Jeong-Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, South Korea.
authors.forename: Jun Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Physiology, College of Medicine, Institute of Neurodegeneration and Neuroregeneration, Hallym University, Chuncheon, South Korea.
authors.forename: Yun Lyul
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, South Korea.
authors.forename: Il-Jun
authors.initials: IJ
authors.lastname: Kang
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
keywords: cell proliferation; dentate gyrus; granule cell layer; nerve regeneration; neural regeneration; neuroblast differentiation; neuroblast migration; neurogenesis; scopolamine