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Modulation of N-Methyl-D-Aspartate Receptors (NMDAR), Bcl-2 and C-Fos Gene Expressions on Exposure to Individual and Mixtures of Low Concentration Metals in Zebrafish (Danio rerio)

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Abstract

Currently, there is limited information on the toxicity of low concentration of metal mixtures in the environment. Of particular interest is the effect of low levels of metal mixtures on neurodevelopment of aquatic organisms. This study reports the neurological gene expressions after exposing zebrafish embryos to low concentration toxic heavy metals, 120 h post fertilization (hpf). Embryos were exposed to low concentration individual and mixtures of lead (Pb), mercury (Hg), arsenic (As), and cadmium (Cd). Quantitative real-time PCR was used to assess gene expressions. The findings of this study confirmed that exposure to low concentration heavy metals upregulated N-methyl-D-aspartate (NMDA) receptor subunits NMDAR2A (NR2A), NMDAR2B (NR2B), and NMDAR2D (NR2D) and B cell lymphoma (Bcl-2) genes. NR2A genes were significantly upregulated by 90 and 74%, respectively, on exposure to Pb + As and Pb + Cd. NR2B genes were upregulated by 85.3, 68.6, 62.7, and 62.7% on exposure to As, Pb + Hg, Pb + As, and Pb + Cd, respectively. Exposure to As, Pb + Cd, and Pb + Hg + As significantly upregulated Bcl-2 genes by 2.01-, 1.84-, and 1.80-fold, respectively. NR1A and C-fos gene expressions were not significantly different from control. Upregulation of NMDAR subunits and Bcl-2 genes in this study was largely a counter measure against insults from exposure to low concentration heavy metals. Principal component analysis confirmed the influence of low concentration individual and mixtures of Pb, Hg, As, and Cd on gene expression of NMDAR subunits and Bcl-2. These data suggest that altered expression of NMDA receptor subunits and Bcl-2 genes may explain toxicity of low concentration individual and mixtures of Pb, Hg, As, and Cd.

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Acknowledgements

This work was supported financially by the Priority Academic Program Development of Jiangsu Higher Education Institutions, Collaborative Innovation Center of Technology and Material of Water Treatment, Specialized Research Fund for the Doctoral Program of Chinese Universities from the Ministry of Education (20113227110020) and Graduate Innovative Projects in Jiangsu Province (KYLX_1067).

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  1. School of the Environment and Safety Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, Jiangsu, China

    Samuel Jerry Cobbina, Guanghua Mao, Hai Xu, Zhen Zhang, Hongyang Liu, Yanmin Zou & Xiangyang Wu

  2. School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang, 212013, China

    Ting Zhao & Liuqing Yang

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  1. Samuel Jerry Cobbina
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  2. Guanghua Mao
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  3. Ting Zhao
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  5. Zhen Zhang
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Correspondence to Xiangyang Wu.

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Cobbina, S.J., Mao, G., Zhao, T. et al. Modulation of N-Methyl-D-Aspartate Receptors (NMDAR), Bcl-2 and C-Fos Gene Expressions on Exposure to Individual and Mixtures of Low Concentration Metals in Zebrafish (Danio rerio). Arch Environ Contam Toxicol 72, 418–427 (2017). https://doi.org/10.1007/s00244-016-0352-y

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