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Comparison of the Effects of Cuprizone on Demyelination in the Corpus Callosum and Hippocampal Progenitors in Young Adult and Aged Mice

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Abstract

Cuprizone is commonly used to induce neuronal demyelination in mice. In the present study, we compared the cuprizone-induced demyelination in the corpus callosum and investigated the effects of cuprizone on proliferating cells and neuroblasts in the dentate gyrus of young adult and aged mice. 5-week- and 23-month-old mice were fed a normal diet or a 0.2% cuprizone-enriched diet for 5 weeks. Mice fed a cuprizone-supplemented diet showed a significant reduction in myelin basic protein-positive structures in the corpus callosum, with the reduction in myelinated fibers being confirmed by electron microscopic analysis. In addition, we observed a marked increase in Ki67-positive proliferating cells and doublecortin-immunoreactive neuroblasts in young adult mice in response to cuprizone treatment, although not in aged mice, as the basal levels of these cells were significantly lower in these older mice. Furthermore, Ser133-phosphorylated cAMP response element-binding protein (pCREB)-positive nuclei and brain-derived neurotrophic factor (BDNF) protein levels were significantly reduced in young adult mice following cuprizone treatment in young adult, although again not in the aged mice. However, in both young adult and aged mice, there were no significant reductions in hippocampal mature neurons in response to cuprizone treatment. These observations indicate that in the mice of both age groups a cuprizone-supplemented diet contributes to an increase in demyelination in the corpus callosum and neural progenitor cells in the dentate gyrus, although the damage is more pronounced in young adult mice. This demyelination and reduction in neural progenitor cells may be associated with changes in the levels of BDNF and pCREB in the dentate gyrus.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. NRF-2018R1D1A1B07044543). This work was also supported by the Seoul National University Research Grant in 2019. In addition, this study was partially supported by the Research Institute for Veterinary Science of 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

    Kyu Ri Hahn, Woosuk Kim, Hyo Young Jung, In Koo Hwang & Yeo Sung Yoon

  2. Department of Anatomy, College of Veterinary Medicine, and Veterinary Science Research Institute, Konkuk University, Seoul, 05030, South Korea

    Woosuk Kim

  3. Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, South Korea

    Hyo Young Jung

  4. Department of Biomedical Sciences, and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea

    Hyun Jung Kwon

  5. 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

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  1. Kyu Ri Hahn
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Hahn, K.R., Kim, W., Jung, H.Y. et al. Comparison of the Effects of Cuprizone on Demyelination in the Corpus Callosum and Hippocampal Progenitors in Young Adult and Aged Mice. Neurochem Res 47, 1073–1082 (2022). https://doi.org/10.1007/s11064-021-03506-8

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  • DOI: https://doi.org/10.1007/s11064-021-03506-8

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