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Effects of Cu,Zn-Superoxide Dismutase on Cell Proliferation and Neuroblast Differentiation in the Mouse Dentate Gyrus

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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.

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Acknowledgments

The authors would like to thank Mr. Seung Uk Lee and Mrs. Hyun Sook Kim for their technical help in this study. This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0010580), and by a grant (2010K000823) from Brain Research Center of the twenty-first Century Frontier Research Program funded by the Ministry of Education, Science and Technology, the Republic of Korea.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    Dae Young Yoo, Woosuk Kim, Yeo Sung Yoon & In Koo Hwang

  2. Department of Physiology, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea

    Bich Na Shin & In Hye Kim

  3. Department of Biomedical Sciences, and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 200-702, South Korea

    Dae Won Kim & Soo Young Choi

  4. Department of Oral Anatomy, College of Dentistry, Kangneung-Wonju National University, Kangneung, 210-702, South Korea

    Ki-Yeon Yoo

  5. Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon, 200-701, South Korea

    Jung Hoon Choi

  6. Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea

    Choong Hyun Lee & Moo-Ho Won

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  1. Dae Young Yoo
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Correspondence to Moo-Ho Won or In Koo Hwang.

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Yoo, D.Y., Shin, B.N., Kim, I.H. et al. Effects of Cu,Zn-Superoxide Dismutase on Cell Proliferation and Neuroblast Differentiation in the Mouse Dentate Gyrus. Neurochem Res 37, 261–267 (2012). https://doi.org/10.1007/s11064-011-0605-0

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