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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

1
Division of Plastic and Reconstructive Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
2
Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
3
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
4
National Kaohsiung University of Science and Technology, Kaohsiung 83301, Taiwan
5
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
6
College of Medicine, Chang Gung University, Kaohsiung 83301, Taiwan
7
Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
8
Center for Geriatrics and Gerontology and Division of Neurology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
9
Department of Senior Citizen Services, National Tainan Institute of Nursing, Tainan 700, Taiwan
*
Author to whom correspondence should be addressed.
Authors share equal contribution.
Int. J. Environ. Res. Public Health 2020, 17(11), 3919; https://doi.org/10.3390/ijerph17113919
Received: 17 April 2020 / Revised: 23 May 2020 / Accepted: 29 May 2020 / Published: 1 June 2020
(This article belongs to the Special Issue Maternal and Early-Life Nutrition and Health)
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. View Full-Text
Keywords: maternal high-fructose diet; neural stem cell proliferation; neuronal differentiation; histone deacetylase 4; enriched housing maternal high-fructose diet; neural stem cell proliferation; neuronal differentiation; histone deacetylase 4; enriched housing
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Liu, W.-C.; Wu, C.-W.; Hung, P.-L.; Chan, J.Y.H.; Tain, Y.-L.; Fu, M.-H.; Chen, L.-W.; Liang, C.-K.; Hung, C.-Y.; Yu, H.-R.; Chen, I.-C.; Wu, K.L. 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. Int. J. Environ. Res. Public Health 2020, 17, 3919.

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