title: Effects of Cu,Zn-superoxide dismutase on cell proliferation and neuroblast differentiation in the mouse dentate gyrus.
abstract: Oxidative stress is one of the most important factors in reducing adult hippocampal neurogenesis in the adult brain. In this study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) on lipid peroxidation, cell proliferation, and neuroblast differentiation in the mouse dentate gyrus using malondialdehyde (MDA), Ki67, and doublecortin (DCX), respectively. We constructed an expression vector, PEP-1, fused PEP-1 with SOD1, and generated PEP-1-SOD1 fusion protein. We administered PEP-1 and 100 or 500 μg PEP-1-SOD1 intraperitoneally once a day for 3 weeks and sacrificed at 30 min after the last administrations. PEP-1 administration did not change the MDA levels compared to those in the vehicle-treated group, while PEP-1-SOD1 treatment significantly reduced MDA levels compared to the vehicle-treated group. In the PEP-1-treated group, the number of Ki67-positive nuclei was similar to that in the vehicle-treated group. In the 100 μg PEP-1-SOD1-treated group, the number of Ki67-positive nuclei was slightly decreased; however, in the 500 μg PEP-1-SOD1-treated group, Ki67-positive nuclei were decreased to 78.5% of the vehicle-treated group. The number of DCX-positive neuroblasts in the PEP-1-treated group was similar to that in the vehicle-treated group. However, the arborization of DCX-positive neuroblasts was significantly decreased in both the 100 and 500 μg PEP-1-SOD1-treated groups compared to that in the vehicle-treated group. The number of DCX-positive neuroblasts with tertiary dendrites was markedly decreased in the 500 μg PEP-1-SOD1-treated group. These results suggest that a SOD1 supplement to healthy mice may not be necessary to modulate cell proliferation and neuroblast differentiation in the dentate gyrus.
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: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.forename: Bich Na
authors.initials: BN
authors.lastname: Shin
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.forename: Woosuk
authors.initials: W
authors.lastname: Kim
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D017931:DNA Primers; D018891:Dentate Gyrus / Q000166:cytology / Q000201:enzymology*; D000089662:Doublecortin Protein; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D013482:Superoxide Dismutase