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Effects of arsenic exposure on d-serine metabolism in the hippocampus of offspring mice at different developmental stages

  • Inorganic compounds
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Abstract

The main purpose of this study was to verify the hypothesis that cognitive dysfunctions induced by arsenic exposure were related to the changes of d-serine metabolism in the hippocampus of offspring mice. Mother mice and their offsprings were exposed to 0, 15, 30 or 60 mg/L sodium arsenite (NaAsO2) through drinking water from the first day of gestation until the end of lactation. d-serine levels in the hippocampus of mice of postnatal day (PND) 10, 20 and 40 were examined by high-performance liquid chromatography. Expressions of serine racemase (SR), d-amino acid oxidase (DAAO), alanine–serine–cysteine transporter-1 (asc-1) and subunits of N-methyl-d-aspartate receptors (NMDARs) in the hippocampus of mice were measured by Western blot and Real-time RT-PCR. Results showed that arsenic exposure significantly decreased d-serine levels of mice exposed to 60 mg/L NaAsO2. Exposure to 60 mg/L NaAsO2 could inhibit both mRNA and protein expression of SR, whereas increase in the protein expression of DAAO, only enhances the mRNA levels of DAAO of PND 20 mice. In addition, arsenic exposure could upregulate protein expression of asc-1. The mRNA and protein levels of NR1, NR2A and NR2B in the hippocampus of mice were down-regulated by arsenic. Findings from this study suggested that SR might play an important role in the reduction of d-serine levels caused by arsenic exposure, which might further influence the levels of NMDAR subunits especially on PND20, and then might disturb the function of NMDARs and cause the deficits of learning and memory ability of offspring mice.

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Funding

The work was supported by the National Natural Science Foundation of China (no. 81202158, 81872570) and Liaoning Provincial Natural Science Foundation (no. 20170540868).

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Authors and Affiliations

  1. Department of Occupational and Environmental Health, School of Public Health, Shenyang Medical College, No. 146 Huanghe North Street, Yuhong District, Shenyang, 110034, Liaoning, People’s Republic of China

    Yan Wang, Xiaoxia Yang, Huan Wang, Yingying Qi & Mengyao Geng

  2. Department of Toxicology, School of Public Health, Shenyang Medical College, Shenyang, Liaoning, People’s Republic of China

    Haiyang Yu

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Wang, Y., Yang, X., Yu, H. et al. Effects of arsenic exposure on d-serine metabolism in the hippocampus of offspring mice at different developmental stages. Arch Toxicol 94, 77–87 (2020). https://doi.org/10.1007/s00204-019-02616-1

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