甲基汞暴露对出生后大鼠学习记忆及NMDA受体表达的影响

Effects of Postnatal Exposure to Methylmercury on Learning, Memory and Expression of NMDA Receptor of Rats

[目的]研究甲基汞暴露对出生后不同生长期大鼠学习记忆能力及N-甲基-D-天冬氨酸(NMDA)受体mRNA水平表达的影响。[方法]将出生后大鼠随机分组,即5 mL/kg生理盐水组和5 mg/kg氯化甲基汞(MMC)染毒组,其中染毒组按生后不同生长时期分4个亚组,即PND7、PND14、PND28和PND60组,连续7 d灌胃染毒。采用Morris水迷宫试验检测大鼠学习记忆功能的改变,用原子荧光光度计检测脑组织汞含量、用逆转录-聚合酶链式反应(RT-PCR)特异性扩增受体NMDA的2A、2B、2C亚基,半定量分析PCR产物凝胶电泳结果。[结果]各染毒亚组在染毒后脑组织中汞含量明显高于对照组(P<0.01),水迷宫试验后,PND28皮质组织及PND60脑组织中汞含量明显高于对照组(P<0.01);Morris水迷宫试验结果显示,PND7、PND14染毒大鼠水迷宫测试潜伏期明显长于对照组(P<0.01);PND14染毒亚组海马和皮质中NR2A mRNA的表达明显低于对照组(P<0.05);PND14染毒亚组海马中NR2B mRNA表达明显低于对照组(P<0.01);PND14染毒亚组海马和皮质以及PND28亚组皮质中NR2C mRNA表达明显高于对照组(P<0.01)。[结论]甲基汞对出生后1、2周的大鼠学习记忆功能有明显影响,其影响与脑组织NMDA受体2亚基mRNA表达变化有关。

[ Objective ] To study the effects of postnatal exposure to methylmereury on learning, memory and the expression of N-methyl-D-aspartate （NMDA） receptor mRNA in rats. [ Methods ] The rats treated with 5 mg/kg methylmereury chloride （MMC） were taken as MMC-treated group and those with 5 mL/kg sodium chloride solution as control group, by oral for 7 consecutive days. The MMC-treated group was subdivided by different postnatal periods （PND7, PND14, PND28 and PNI）60） and tested for learning and memory with Morris water maze. The concentration of mercury was checked by atomic fluorescence spectrometry （AFS）. Expression of NMDA receptor 2A, 2B and 2C subunits were measured by semi-quantitative reverse transcript polymerasechain reaction （RT-PCR）. [ Results ] Mercury concentrations in both hippoeampus and cerebral cortex were elevated significantly in the MMC-treated group （P〈0.01）; while the level of mercury in cortex of PND28 and both cortex and hippoeampus of PND60 was significantly higher in comparison with that of the control （P〈 0.01）. The latency of PND7 and PND14 MMC-treated rats in water maze was much longer than that of the control （P〈0.01）. The levels of NR2A mRNA were significantly decreased in both hippoeampus and cortex of PND14 subgroup （P 〈 0.05）; the levels of NR2B mRNA were significantly reduced in hippoeampus of PND14 subgroup （P〈0.01）; and an increment ofNR2C mRNA was observed in hippoeampus of PND14 and in cortex of PND14 and PND28 subgroups （P 〈 0.01）. [ Conclusion ] The first two weeks after birth is critical to methylmereury exposure, which would result in the impairment of learning and memory ability for life span. The altering expression of NR2 subunits is an influencing factor.