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Zinc Deficiency Reduces Neurogenesis Accompanied by Neuronal Apoptosis Through Caspase-Dependent and -Independent Signaling Pathways

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Abstract

Dietary zinc deficiency may affect zinc homeostasis in the brain and lead to reductions of neurogenesis and neuronal survival. However, the mechanisms responsible for the effects of zinc deficiency on hippocampal neurogenesis and neuronal death remain obscure. In the present study, young CD-1 mice were fed with zinc-deficient diet (0.85 ppm) for 5 weeks. The vesicular zinc was reduced at CA1 and CA3 regions of the hippocampus in zinc-deficient mice. The significant decreased zinc ions was associated with a reduction in proliferating cells labeled with bromo-deoxyuridine (BrdU) and immature neurons labeled with doublecortin (DCX) immunoreactivity in the dentate gyrus of the hippocampus. The processes of DCX-positive neurons were shortened, and flexuously went through into the granular cell layer in zinc-deficient hippocampus. There was also a conspicuous increase in the number of TUNEL-positive cells in the hippocampus after zinc-deficient diet treatment. Meanwhile, the apoptosis proteins, including Fas, Fas ligand (FasL), apoptosis inducing factor (AIF), and caspase-3, were significantly activated in zinc-deficient mouse hippocampus. These data suggest that chronic treatment with zinc-deficient diet results in reduction in hippocampal neurogenesis and increases neuronal apoptosis, indicating that zinc deficiency is associated with destroying structural plasticity in the hippocampus.

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Acknowledgments

The study was supported by the Natural Science Foundation of China (30370452, 30770680), the Program for New Century Excellent Talents in University (NCET-04-0288), the China Postdoctoral Science Foundation (2005037008), and the Specialized Research Fund for the Doctoral Program of Higher Education (SRFDP-20060159001).

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Authors and Affiliations

  1. Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, 110001, People’s Republic of China

    Hui-Ling Gao & Zhan-You Wang

  2. College of Basic Medical Sciences, China Medical University, Shenyang, 110001, People’s Republic of China

    Hui-Ling Gao, Wei Zheng, Na Xin, Zhi-Hong Chi, Zhen-Yu Wang & Zhan-You Wang

  3. School of Public Health, China Medical University, Shenyang, 110001, People’s Republic of China

    Jie Chen

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  1. Hui-Ling Gao
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Correspondence to Zhan-You Wang.

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Gao, HL., Zheng, W., Xin, N. et al. Zinc Deficiency Reduces Neurogenesis Accompanied by Neuronal Apoptosis Through Caspase-Dependent and -Independent Signaling Pathways. Neurotox Res 16, 416–425 (2009). https://doi.org/10.1007/s12640-009-9072-7

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