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Differential Effects of Low- and High-dose Zinc Supplementation on Synaptic Plasticity and Neurogenesis in the Hippocampus of Control and High-fat Diet-fed Mice

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Abstract

In the present study, we investigated the concentration-dependent effect of zinc (Zn) supplementation on the adult hippocampus in a high-fat diet (HFD)-fed obese mouse model. Four-weeks after HFD- and control diet (CD)-feeding, mice were provided with low (15 ppm) or high (60 ppm) doses of Zn in their drinking water for additional 4 more weeks along with their respective diets. Compared to the CD-fed mice, HFD-feeding elicited the reduction of neurogenic markers such as nestin, Ki67, doublecortin (DCX), and 5-bromo-2′-deoxyuridine (BrdU) in the dentate gyrus. Additionally, HFD-feeding reduced the levels of synaptic markers (synaptophysin and N-methyl-d-aspartate receptor) and brain-derived neurotrophic factor (BDNF), while lipid peroxidation was significantly increased in the hippocampus of HFD-fed mice. Against detrimental effects of high-dose Zn, low-dose Zn supplementation in CD-fed mice did not yield any remarkable changes in these parameters. Interestingly, administration of low doses of Zn to HFD-induced obese mice prominently ameliorated HFD-induced changes in neurogenic, synaptic plasticity markers and BDNF levels as well as lipid peroxidation in the hippocampus. In contrast, high-dose Zn supplementation in HFD-fed mice exacerbated the reduction of markers for neurogenesis and synaptic plasticity as well as BDNF levels, but not 4-HNE levels, in the hippocampus. These results suggest that low-dose Zn supplementation in obese mice could reverse the HFD-induced reduction in neurogenic and synaptic marker proteins in the hippocampus by reducing lipid peroxidation and improving BDNF expression, while high-dose Zn supplementation exacerbates the reduction of neurogenesis by affecting synaptic markers and BDNF levels in the hippocampus.

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Acknowledgements

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A1A01059314) and was supported by Korea Mouse Phenotyping Project (NRF-2015M3A9D5A01076747) of the Ministry of Science, ICT and Future Planning through the National Research Foundation (NRF), Korea. This study was partially supported by the Research Institute for Veterinary Science, Seoul National University.

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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, 08826, South Korea

    Sung Min Nam, Jong Whi Kim, Dae Young Yoo, Hyo Young Jung, In Koo Hwang, Je Kyung Seong & Yeo Sung Yoon

  2. Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, 05030, South Korea

    Sung Min Nam

  3. Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea

    Hyun Jung Kwon & Dae Won Kim

  4. KMPC (Korea Mouse Phenotyping Center), Seoul National University, Seoul, 08826, South Korea

    In Koo Hwang, Je Kyung Seong & Yeo Sung Yoon

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  1. Sung Min Nam
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Nam, S.M., Kim, J.W., Kwon, H.J. et al. Differential Effects of Low- and High-dose Zinc Supplementation on Synaptic Plasticity and Neurogenesis in the Hippocampus of Control and High-fat Diet-fed Mice. Neurochem Res 42, 3149–3159 (2017). https://doi.org/10.1007/s11064-017-2353-2

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  • DOI: https://doi.org/10.1007/s11064-017-2353-2

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