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Metformin Normalizes Type 2 Diabetes-Induced Decrease in Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus

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Abstract

In this study, we observed the effects of metformin, one of the most widely prescribed drugs for the treatment of type 2 diabetes, on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus (SZDG) in Zucker diabetic fatty (ZDF) rats, which are a model for type 2 diabetes. For this, metformin was administered orally once a day to 14-week-old ZDF rats for 2 weeks and the animals were sacrificed at 16 weeks of age. During this period, blood glucose levels were higher in the vehicle-treated ZDF rats than in the Zucker lean control (ZLC) rats. Metformin treatment significantly decreased the blood glucose levels from 15.5 weeks of age. In the SZDG, Ki67 (a marker for cell proliferation)- and doublecortin (DCX, a marker for differentiated neuroblasts)-immunoreactive cells were much lower in the vehicle-treated ZDF rats than in the ZLC rats. In the metformin-treated ZDF group, Ki67- and DCX-immunoreactive cells were significantly increased in the SZDG compared to those in the vehicle-treated ZDF group. These results suggest that diabetes significantly reduces cell proliferation and neuroblast differentiation in the SZDG and that metformin treatment normalizes the reduction of cell proliferation and neuroblast differentiation in the SZDG in diabetic rats.

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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 work was supported by the National Research Foundation of Korea grant funded by the Korea government (MEST) (No. 2009-0071833).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    In Koo Hwang, Il Yong Kim, Eun Jung Joo, Jae Hoon Shin, Ji Won Choi, Yeo Sung Yoon & Je Kyung Seong

  2. Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea

    Moo-Ho Won

  3. Interdisciplinary Program in Brain Science, Seoul National University, Seoul, 151-742, South Korea

    In Koo Hwang

  4. Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea

    Moo-Ho Won

  5. Interdisciplinary Program for Bioinformatics, Seoul National University, Seoul, 151-742, Korea

    Je Kyung Seong

  6. Program for Cancer Biology, Cancer Research Institute, College of Medicine, Seoul National University, Seoul, 151-742, Korea

    Je Kyung Seong

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  1. In Koo Hwang
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  2. Il Yong Kim
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  3. Eun Jung Joo
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  5. Ji Won Choi
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  6. Moo-Ho Won
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  7. Yeo Sung Yoon
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Correspondence to Yeo Sung Yoon or Je Kyung Seong.

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Hwang, I.K., Kim, I.Y., Joo, E.J. et al. Metformin Normalizes Type 2 Diabetes-Induced Decrease in Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus. Neurochem Res 35, 645–650 (2010). https://doi.org/10.1007/s11064-009-0115-5

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