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Repeated Administration of PEP-1-Cu,Zn-Superoxide Dismutase and PEP-1-Peroxiredoxin-2 to Senescent Mice Induced by d-galactose Improves the Hippocampal Functions

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Abstract

Oxidative stress initiates age-related reduction in hippocampal neurogenesis and the use of antioxidants has been proposed as an effective strategy to prevent or attenuate the reduction of neurogenesis in the hippocampus. In the present study, we investigated the effects of Cu,Zn-superoxide dismutase (SOD1) and/or peroxiredoxin-2 (PRX2) on cell proliferation and neuroblast differentiation in the dentate gyrus in a model of d-galactose-induced aging model. For this study, we constructed an expression vector, PEP-1, fused PEP-1 with SOD1 or PRX2, and generated PEP-1-SOD1 and PEP-1-PRX2 fusion protein. The aging model was induced by subcutaneous injection of d-galactose (100 mg/kg) to 6-week-old male mice for 10 weeks. PEP-1, PEP-1-SOD1 and/or PEP-1-PRX2 fusion protein was intraperitoneally administered to these mice at 13-week-old once a day for 3 weeks and sacrificed at 30 min after the last administrations. The administration of PEP-1-SOD1 and/or PEP-1-PRX2 significantly improved d-galactose-induced deficits on the escape latency, swimming speeds, platform crossings, spatial preference for the target quadrant in Morris water maze test. In addition, the administration of PEP-1-SOD1 and/or PEP-1-PRX2 ameliorated d-galactose-induced reductions of cell proliferation and neuroblast differentiation in the dentate gyrus and significantly reduced d-galactose-induced lipid peroxidation in the hippocampus. These effects were more prominent in the PEP-1-SOD1-treated group with PEP-1-PRX2. These results suggest that a SOD1 and/or PRX2 supplement to aged mice could improve the memory deficits, cell proliferation and neuroblast differentiation in the dentate gyrus of d-galactose induced aged mice by reducing lipid peroxidation.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

CREB:

cAMP response element-binding protein

DCX:

Doublecortin

d-gal:

d-galactose

LTP:

Long-term potentiation

MDA:

Malondialdehyde

PCR:

Polymerase chain reaction

PB:

Phosphate-buffer

PBS:

Phosphate-buffered saline

PRX:

Peroxiredoxin

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SOD1:

Cu,Zn-superoxide dismutase

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A2006995) and was supported by 2010 Research Grant from Kangwon National University.

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Authors and Affiliations

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

    Jung Hoon Choi

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

    Dae Won Kim, Hoon Jae Jeong & Soo Young Choi

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

    Dae Young Yoo, Woosuk Kim, Hyo Young Jung, Sung Min Nam, Jong Hwi Kim, Yeo Sung Yoon & In Koo Hwang

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  1. Jung Hoon Choi
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Correspondence to Soo Young Choi or In Koo Hwang.

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Jung Hoon Choi, Dae Won Kim and Dae Young Yoo have contributed equally to this work.

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Choi, J.H., Kim, D.W., Yoo, D.Y. et al. Repeated Administration of PEP-1-Cu,Zn-Superoxide Dismutase and PEP-1-Peroxiredoxin-2 to Senescent Mice Induced by d-galactose Improves the Hippocampal Functions. Neurochem Res 38, 2046–2055 (2013). https://doi.org/10.1007/s11064-013-1112-2

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