title: Effects of gintonin-enriched fraction on hippocampal cell proliferation in wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease.
abstract: We previously showed that gintonin, an exogenous lysophosphatidic acid (LPA) receptor ligand, attenuated β-amyloid plaque formation in the cortex and hippocampus, and restored β-amyloid-induced memory dysfunction. Both endogenous LPA and LPA receptors play a key role in embryonic brain development. However, little is known about whether gintonin can induce hippocampal cell proliferation in adult wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease (AD). In the present study, we examined the effects of gintonin on the proliferation of hippocampal neural progenitor cells (NPCs) in vitro and its effects on the hippocampal cell proliferation in wild-type mice and a transgenic AD mouse model. Gintonin treatment increased 5-bromo-2'-deoxyuridine (BrdU) incorporation in hippocampal NPCs in a dose- and time-dependent manner. Gintonin (0.3 μg/ml) increased the immunostaining of glial fibrillary acidic protein, NeuN, and LPA1 receptor in hippocampal NPCs. However, the gintonin-induced increase in BrdU incorporation and immunostaining of biomarkers was blocked by an LPA1/3 receptor antagonist and Ca2+chelator. Oral administration of the gintonin-enriched fraction (50 and 100 mg/kg) increased hippocampal BrdU incorporation and LPA1/3 receptor expression in adult wild-type and transgenic AD mice. The present study showed that gintonin could increase the number of hippocampal neurons in adult wild-type mice and a transgenic AD mouse model. Our results indicate that gintonin-mediated hippocampal cell proliferation contributes to the gintonin-mediated restorative effect against β-amyloid-induced hippocampal dysfunction. These results support the use of gintonin for the prevention or treatment of neurodegenerative diseases such as AD via promotion of hippocampal neurogenesis.
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, Kangwon National University School of Medicine, Chunchon 24341, Republic of Korea.
authors.forename: Dae-Joong
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Shin
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University, Wonju 26339, Republic of Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Center for Neuroscience, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.affiliation: Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Ik-Hyun
authors.initials: IH
authors.lastname: Cho
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea. Electronic address: kimhc@kangwon.ac.kr.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea. Electronic address: synah@konkuk.ac.kr.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000187:drug effects* / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology*; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D010936:Plant Extracts; D053764:Presenilin-1; C000603040:gintonin; C580804:presenilin 1, mouse
keywords: Alzheimer's disease; Ginseng; Gintonin; Hippocampal neurogenesis; LPA receptor