title: Tanshinone I Enhances Neurogenesis in the Mouse Hippocampal Dentate Gyrus via Increasing Wnt-3, Phosphorylated Glycogen Synthase Kinase-3β and β-Catenin Immunoreactivities.
abstract: Tanshinone I (TsI), a lipophilic diterpene extracted from Danshan (Radix Salvia miltiorrhizae), exerts neuroprotection in cerebrovascular diseases including transient ischemic attack. In this study, we examined effects of TsI on cell proliferation and neuronal differentiation in the subgranular zone (SGZ) of the mouse dentate gyrus (DG) using Ki-67, BrdU and doublecortin (DCX) immunohistochemistry. Mice were treated with 1 and 2 mg/kg TsI for 28 days. In the 1 mg/kg TsI-treated-group, distribution patterns of BrdU, Ki-67 and DCX positive ((+)) cells in the SGZ were similar to those in the vehicle-treated-group. However, in the 2 mg/kg TsI-treated-group, double labeled BrdU(+)/NeuN(+) cells, which are mature neurons, as well as Ki-67(+), DCX(+) and BrdU(+) cells were significantly increased compared with those in the vehicle-treated-group. On the other hand, immunoreactivities and protein levels of Wnt-3, β-catenin and serine-9-glycogen synthase kinase-3β (p-GSK-3β), which are related with morphogenesis, were significantly increased in the granule cell layer of the DG only in the 2 mg/kg TsI-treated-group. Therefore, these findings indicate that TsI can promote neurogenesis in the mouse DG and that the neurogenesis is related with increases of Wnt-3, p-GSK-3β and β-catenin immunoreactivities.
authors.affiliation: Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Bai Hui
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Jeong Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Jae Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Tae-Kyeong
authors.initials: TK
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Tae
authors.affiliation: Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Bich Na
authors.initials: BN
authors.lastname: Shin
authors.affiliation: Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Jong-Dai
authors.initials: JD
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, 24252, South Korea.
authors.forename: Il Jun
authors.initials: IJ
authors.lastname: Kang
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea. mhwon@kangwon.ac.kr.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.affiliation: Department of Physiology, Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 24252, South Korea. yylee@hallym.ac.kr.
authors.forename: Yun Lyul
authors.initials: YL
authors.lastname: Lee
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000089662:Doublecortin Protein; D000071679:Glycogen Synthase Kinase 3 beta / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D060508:Wnt3 Protein / Q000032:analysis / Q000096:biosynthesis*; D051176:beta Catenin / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D045784:Abietanes; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; D051176:beta Catenin; C021751:tanshinone; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Cell proliferation; Neuroblast differentiation; Neurogenesis; Phosphorylated glycogen synthase kinase 3β; Tanshinone I; Wnt-3; β-Catenin