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Effects of arsenic exposure on D-serine metabolism in the hippocampus of offspring mice at different developmental stages.
Archives of Toxicology ( IF 4.8 ) Pub Date : 2019-11-11 , DOI: 10.1007/s00204-019-02616-1
Yan Wang 1 , Xiaoxia Yang 1 , Haiyang Yu 2 , Huan Wang 1 , Yingying Qi 1 , Mengyao Geng 1
Affiliation  

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.

中文翻译:

砷暴露对不同发育阶段后代小鼠海马D-丝氨酸代谢的影响。

这项研究的主要目的是验证以下假设:砷暴露引起的认知功能障碍与后代小鼠海马中D-丝氨酸代谢的变化有关。从妊娠的第一天到哺乳结束,母鼠及其后代都通过饮用水暴露于0、15、30或60 mg / L的亚砷酸钠(NaAsO2)中。通过高效液相色谱法检查出生后第10、20和40天(PND)小鼠海马中的D-丝氨酸水平。小鼠海马中丝氨酸消旋酶(SR),D-氨基酸氧化酶(DAAO),丙氨酸-丝氨酸-半胱氨酸转运蛋白-1(asc-1)和N-甲基-D-天冬氨酸受体(NMDARs)的亚单位表达为通过蛋白质印迹和实时RT-PCR测定。结果表明,砷暴露显着降低了暴露于60 mg / L NaAsO2的小鼠的D-丝氨酸水平。暴露于60 mg / L NaAsO2可以同时抑制SR的mRNA和蛋白表达,而增加DAAO的蛋白表达只会增加PND 20小鼠DAAO的mRNA水平。此外,砷暴露可能会上调asc-1的蛋白质表达。砷下调小鼠海马NR1,NR2A和NR2B的mRNA和蛋白水平。这项研究的结果表明,SR可能在降低砷暴露引起的D-丝氨酸水平方面起重要作用,这可能进一步影响NMDAR亚基的水平,尤其是PND20,然后可能会扰乱NMDAR的功能并导致缺陷后代小鼠的学习和记忆能力 暴露于60 mg / L NaAsO2可以同时抑制SR的mRNA和蛋白表达,而增加DAAO的蛋白表达只会增加PND 20小鼠DAAO的mRNA水平。此外,砷暴露可能会上调asc-1的蛋白表达。砷下调小鼠海马NR1,NR2A和NR2B的mRNA和蛋白水平。这项研究的结果表明,SR可能在降低砷暴露引起的D-丝氨酸水平方面起重要作用,这可能进一步影响NMDAR亚基的水平,尤其是PND20,然后可能会扰乱NMDAR的功能并导致缺陷后代小鼠的学习和记忆能力 暴露于60 mg / L NaAsO2可以同时抑制SR的mRNA和蛋白表达,而增加DAAO的蛋白表达只会增加PND 20小鼠DAAO的mRNA水平。此外,砷暴露可能会上调asc-1的蛋白表达。砷下调小鼠海马NR1,NR2A和NR2B的mRNA和蛋白水平。这项研究的结果表明,SR可能在降低砷暴露引起的D-丝氨酸水平方面起重要作用,这可能进一步影响NMDAR亚基的水平,尤其是PND20,然后可能会扰乱NMDAR的功能并导致缺陷后代小鼠的学习和记忆能力 仅增加PND 20小鼠DAAO的mRNA水平。此外,砷暴露可能会上调asc-1的蛋白表达。砷下调小鼠海马NR1,NR2A和NR2B的mRNA和蛋白水平。这项研究的结果表明,SR可能在降低砷暴露引起的D-丝氨酸水平方面起重要作用,这可能进一步影响NMDAR亚基的水平,特别是在PND20上,然后可能会扰乱NMDAR的功能并导致缺陷后代小鼠的学习和记忆能力 仅增加PND 20小鼠DAAO的mRNA水平。此外,砷暴露可能会上调asc-1的蛋白表达。砷下调小鼠海马NR1,NR2A和NR2B的mRNA和蛋白水平。这项研究的结果表明,SR可能在降低砷暴露引起的D-丝氨酸水平方面起重要作用,这可能进一步影响NMDAR亚基的水平,特别是在PND20上,然后可能会扰乱NMDAR的功能并导致缺陷后代小鼠的学习和记忆能力
更新日期:2019-11-11
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