砷暴露对仔代小鼠海马N-甲基-D-天冬氨酸受体水平的影响

Effects of arsenic exposure on level of NMDAR in hippocampus of offspring mice

目的研究砷暴露对不同发育阶段小鼠仔鼠海马N-甲基-D-天冬氨酸受体(NMDAR)水平的影响,探讨砷暴露引起学习记忆能力损伤的可能机制。方法建立不同发育阶段小鼠仔鼠砷暴露模型,砷暴露浓度分别为0、15、30和60 mg/L,记录体重,分别于仔鼠出生后(postnatal day,PND)10、20、40 d取脑组织并分离海马,采用RT-PCR检测NMDAR亚单位NR1、NR2A和NR2B m RNA水平。结果 60 mg/L砷暴露组仔鼠PND20的体重低于对照组和15 mg/L组,30、60 mg/L砷暴露组仔鼠PND40的体重低于对照组,差异均有统计学意义(P<0.05)。各浓度砷暴露组仔鼠PND20的海马NR1和NR2B m RNA水平均低于对照组,60 mg/L砷暴露组仔鼠PND20的海马NR2A水平低于对照组;60 mg/L砷暴露组仔鼠PND40的海马NR1、NR2A和NR2B m RNA水平低于对照组,差异有统计学意义(P<0.05)。结论砷暴露可使仔鼠海马NMDAR亚单位的水平降低,进而可能影响仔鼠的学习记忆能力。

Objective To investigate the impairment mechanism of learning and memory ability induced by arsenite through studying the effects of arsenite on N-methyl-D-aspartic acid receptor （NMDAR） in the hippocampus of offspring mice at different developmental stages. Methods The model of offspring mice exposed to arsenite was set up through freely drinking water at the doses of O, 15, 30 and 60 mg/L arsenite respectively. At postnatal day （PND） 10, 20 or 40, and the hippocampus were collected. The levels of NR1, NR2A and NR2B mRNA were measured by RT-PCR. Results At PND20, the weight of pups exposed to 60 mg/L arsenite was significantly lower than that in control group and 15 mg/L NaAsOz-treated group （P〈0.05）; At PND40, the weight of pups exposed to 30 and 60 mg/L arsenite was much lower than that in control group （P〈0.05）; At PND20, compared with the control group, the levels of NR1 and NR2B in the hippocampus of offspring mice exposed to arsenite obviously decreased （P〈0.05）, the level of NR2A in the hippocampus of pups exposed to 60 mg/L arsenite was significantly lower （P〈0.05）; At PND40, the levels of NR1, NR2A and NR2B in the hippocampus of pups exposed to arsenite were significantly lower than those in control group （P〈0.05）. Conclusion Arsenite may affect the levels of NMDAR subunits in the hippocampus of offspring mice and further impair the learning and memory ability.