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Reduced Cell Proliferation and Neuroblast Differentiation in the Dentate Gyrus of High Fat Diet-Fed Mice are Ameliorated by Metformin and Glimepiride Treatment

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Abstract

We investigated the effects of a high-fat diet (HFD) and the subsequent treatment of metformin (met) and glimepiride (glim), which are widely prescribed for type 2 diabetes, on cell proliferation and neuroblast differentiation using Ki67 and doublecortin (DCX) immunohistochemistry, respectively. Animals were fed low-fat diet (LFD) or HFD for 8 weeks. After 5 weeks of the HFD treatment, met alone or met + glim was administered orally once a day for 3 weeks. Body weight and food intake were much higher in the HFD + vehicle-treated group than the LFD-treated group. The administration of met or met + glim to the HFD-treated group resulted in a decrease in weight gain and food intake. Ki67-immunoreactive (+) nuclei, DCX+ neuroblasts and brain-derived neurotrophic factor (BDNF) protein levels were markedly decreased in the dentate gyrus (DG) of the HFD + vehicle-treated group compared to the LFD-treated group. The administration of met or met + glim to the HFD-treated group prevented the reduction of Ki67+ nuclei, DCX+ neuroblasts, BDNF levels in the DG. The intraventricular injection of K252a (a BDNF receptor blocker) to the HFD-treated group treated met or met + glim distinctively lowered the reduction of cell proliferation and neuroblast differentiation induced by HFD. These results suggest that a HFD significantly reduces cell proliferation and neuroblast differentiation by reducing BDNF levels and these effects are ameliorated by treatment with met or met + glim.

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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 Research Institute for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

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

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

    Ki-Yeon Yoo

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

    Choong Hyun Lee & Moo-Ho Won

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

    Jung Hoon Choi

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  1. Dae Young Yoo
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Correspondence to In Koo Hwang or Yeo Sung Yoon.

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Yoo, D.Y., Kim, W., Nam, S.M. et al. Reduced Cell Proliferation and Neuroblast Differentiation in the Dentate Gyrus of High Fat Diet-Fed Mice are Ameliorated by Metformin and Glimepiride Treatment. Neurochem Res 36, 2401–2408 (2011). https://doi.org/10.1007/s11064-011-0566-3

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  • DOI: https://doi.org/10.1007/s11064-011-0566-3

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