title: Effects of aluminum on the reduction of neural stem cells, proliferating cells, and differentiating neuroblasts in the dentate gyrus of D-galactose-treated mice via increasing oxidative stress.
abstract: Aluminum (Al) accumulation increases with aging, and long-term exposure to Al is regarded as a risk factor for Alzheimer's disease. In this study, we investigated the effects of Al and/or D-galactose on neural stem cells, proliferating cells, differentiating neuroblasts, and mature neurons in the hippocampal dentate gyrus. AlCl3 (40 mg/kg/day) was intraperitoneally administered to C57BL/6J mice for 4 weeks. In addition, vehicle (physiological saline) or D-galactose (100 mg/kg) was subcutaneously injected to these mice immediately after AlCl3 treatment. Neural stem cells, proliferating cells, differentiating neuroblasts, and mature neurons were detected using the relevant marker for each cell type, including nestin, Ki67, doublecortin, and NeuN, respectively, via immunohistochemistry. Subchronic (4 weeks) exposure to Al in mice reduced neural stem cells, proliferating cells, and differentiating neuroblasts without causing any changes to mature neurons. This Al-induced reduction effect was exacerbated in D-galactose-treated mice compared to vehicle-treated adult mice. Moreover, exposure to Al enhanced lipid peroxidation in the hippocampus and expression of antioxidants such as Cu, Zn- and Mn-superoxide dismutase in D-galactose-treated mice. These results suggest that Al accelerates the reduction of neural stem cells, proliferating cells, and differentiating neuroblasts in D-galactose-treated mice via oxidative stress, without inducing loss in mature neurons.
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Nam
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.
authors.forename: Jong Whi
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.
authors.forename: Woosuk
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.
authors.forename: Hyo Young
authors.initials: HY
authors.lastname: Jung
authors.affiliation: Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|Korea Mouse Phenotyping Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|Korea Mouse Phenotyping Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.|Korea Mouse Phenotyping Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Koreaiversity, Seoul 08826, Korea.
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D005690:Galactose / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology
chemical_list: D000975:Antioxidants; D000535:Aluminum; D005690:Galactose
keywords: D-galactose; adult neurogenesis; aluminum; hippocampus; oxidative stress