title: Hippophae rhamnoides L. leaves extract enhances cell proliferation and neuroblast differentiation through upregulation of intrinsic factors in the dentate gyrus of the aged gerbil.
abstract: BACKGROUND
  Hippophae rhamnoides L. (HL) exerts antioxidant activities against various oxidative stress conditions. In this study, we investigated effects of extract from HL leaves (HLE) on cell proliferation and neuroblast differentiation in the subgranular zone (SGZ) of the dentate gyrus (DG) of aged gerbils.
  
  
  METHODS
  Aged gerbils (24 months) were divided into vehicle (saline)-treated- and HLE-treated-groups. The vehicle and HLE were orally administered with 200 mg/kg once a day for 20 days before sacrifice. Cell proliferation and neuroblast differentiation were examined in the DG using Ki67 and doublecortin (DCX), respectively. We also observed changes in immunoreactivities of superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2), brain-derived neurotrophic factor (BDNF), and phospho-glycogen synthase kinase-3-beta (p-GSK-3β) to examine their relation with neurogenesis using immunohistochemistry.
  
  
  RESULTS
  The administration of HLE significantly increased the number of Ki67-positive cells and DCX-positive neuroblasts with well-developed processes in the SGZ of the DG of the HLE-treated-group. In addition, immunoreactivities of SOD1, SOD2, BDNF, and p-GSK-3β were significantly increased in granule and polymorphic cells of the DG in the HLE-treated-group compared with those in the vehicle-treated-group.
  
  
  CONCLUSIONS
  HLE treatment significantly increased cell proliferation and neuroblast differentiation, showing that immunoreactivities of SOD1, SOD2, BDNF, and p-GSK-3β were significantly increased in the DG. These indicate that increased neuroblast differentiation neurogenesis may be closely related to upregulation of SOD1, SOD2, BDNF, and p-GSK-3β in aged gerbils.
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Bai Hui
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jeong-Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Institute of Integrative Traditional & Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China.
authors.forename: Bing Chun
authors.initials: BC
authors.lastname: Yan
authors.affiliation: Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Samsung Herb Medicine Company Limited, 304 BIO-1dong ChunCheon Biotechnology Innovation Center, Chuncheon 200-957, South Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: ChunCheon Biotechnology Innovation Center, Chuncheon 200-957, South Korea.
authors.forename: Sang-No
authors.initials: SN
authors.lastname: Han
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Yun Lyul
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Oriental Bio-herb Research Institute, Kangwon National University, Chuncheon 200-701, South Korea. Email: kimmjo@kangwon.ac.kr.
authors.forename: Myong Jo
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Email: mhwon@kangwon.ac.kr.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism*; D005849:Gerbillinae; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D031281:Hippophae / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D007437:Intrinsic Factor / Q000378:metabolism*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007437:Intrinsic Factor; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2