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Environmental Stimulation Counteracts the Suppressive Effects of Maternal High-Fructose Diet on Cell Proliferation and Neuronal Differentiation in the Dentate Gyrus of Adult Female Offspring via Histone Deacetylase 4

Author

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  • Wen-Chung Liu

    (Division of Plastic and Reconstructive Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
    Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
    Authors share equal contribution.)

  • Chih-Wei Wu

    (Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
    National Kaohsiung University of Science and Technology, Kaohsiung 83301, Taiwan
    Authors share equal contribution.)

  • Pi-Lien Hung

    (Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan)

  • Julie Y. H. Chan

    (Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan)

  • You-Lin Tain

    (Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
    Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
    College of Medicine, Chang Gung University, Kaohsiung 83301, Taiwan)

  • Mu-Hui Fu

    (Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan)

  • Lee-Wei Chen

    (Division of Plastic and Reconstructive Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan)

  • Chih-Kuang Liang

    (Center for Geriatrics and Gerontology and Division of Neurology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan)

  • Chun-Ying Hung

    (Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan)

  • Hong-Ren Yu

    (Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan)

  • I-Chun Chen

    (Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan)

  • Kay L.H. Wu

    (Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
    Department of Senior Citizen Services, National Tainan Institute of Nursing, Tainan 700, Taiwan)

Abstract

Maternal high-fructose diets (HFD) impair the learning and memory capacity of adult female offspring via histone deacetylase 4 (HDAC4). Hippocampal adult neurogenesis is important for supporting the function of existing neural circuits. In this study, we investigated the effects of maternal HFD on hippocampal neural stem cell (NSC) proliferation and neuronal differentiation in adult offspring. Increased nuclear HDAC4 enzyme activity was detected in the hippocampus of HFD female offspring. The Western blot analyses indicated that the expressions of sex-determining region Y box2 (SOX2) and the transcription factor Paired Box 6 (PAX6), which are critical for the progression of NSC proliferation and differentiation, were downregulated. Concurrently, the expression of Ki67 (a cellular marker for proliferation) and doublecortin (DCX), which are related to NSC division and neuronal differentiation, was suppressed. Intracerebroventricular infusion with class II HDAC inhibitor (Mc1568, 4 weeks) led to the upregulation of these proteins. Environmental stimulation reversed the expression of Ki67 and DCX and the counts of Ki67- and DCX-positive cells in the hippocampi of HFD offspring as a result of providing the enriched housing for 4 weeks. Together, these results demonstrate that the suppressive effects of maternal HFD on hippocampal NSC proliferation and neuronal differentiation are reversibly mediated through HDAC4 and can be effectively reversed by environmental stimulation. The advantageous effects of environmental enrichment were possibly mediated by HDAC4 suppression.

Suggested Citation

  • Wen-Chung Liu & Chih-Wei Wu & Pi-Lien Hung & Julie Y. H. Chan & You-Lin Tain & Mu-Hui Fu & Lee-Wei Chen & Chih-Kuang Liang & Chun-Ying Hung & Hong-Ren Yu & I-Chun Chen & Kay L.H. Wu, 2020. "Environmental Stimulation Counteracts the Suppressive Effects of Maternal High-Fructose Diet on Cell Proliferation and Neuronal Differentiation in the Dentate Gyrus of Adult Female Offspring via Histo," IJERPH, MDPI, vol. 17(11), pages 1-15, June.
    • Handle: RePEc:gam:jijerp:v:17:y:2020:i:11:p:3919-:d:365957
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    References listed on IDEAS

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    1. Gerd Kempermann & H. Georg Kuhn & Fred H. Gage, 1997. "More hippocampal neurons in adult mice living in an enriched environment," Nature, Nature, vol. 386(6624), pages 493-495, April.
    2. Henriette van Praag & Alejandro F. Schinder & Brian R. Christie & Nicolas Toni & Theo D. Palmer & Fred H. Gage, 2002. "Functional neurogenesis in the adult hippocampus," Nature, Nature, vol. 415(6875), pages 1030-1034, February.
    3. Andre Fischer & Farahnaz Sananbenesi & Xinyu Wang & Matthew Dobbin & Li-Huei Tsai, 2007. "Recovery of learning and memory is associated with chromatin remodelling," Nature, Nature, vol. 447(7141), pages 178-182, May.
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    Cited by:

    1. Li-Tung Huang, 2020. "Maternal and Early-Life Nutrition and Health," IJERPH, MDPI, vol. 17(21), pages 1-4, October.

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