慢性铝暴露对小鼠学习记忆及tau蛋白磷酸化的影响
Effects of Chronic Aluminum Exposure on Learning and Memory and the Phosphorylation of Tau Protein in Mice
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摘要:
目的 探讨慢性铝暴露对小鼠学习记忆及tau蛋白磷酸化水平的影响。 方法 将氯化铝(AlCl3)混入饲料中喂养小鼠,分为高、中、低剂量组,剂量分别为120.0、12.0、1.2 mg(/kg& #183;d),对照组正常饲养,每组各10只。染毒期为1年。用Morris水迷宫系统检测小鼠的认知功能,采用电感耦合等离子质谱法测定脑铝含量,免疫印迹法检测小鼠脑组织中总tau蛋白以及tau蛋白在Thr181、Thr231、Ser262和Ser396位点的磷酸化表达。 结果 Morris水迷宫试验,中、高剂量组水迷宫潜伏期高于对照组(P<0.05),高、中剂量组穿越平台的次数与对照组相比明显减少(P<0.05)。高、中、低剂量组小鼠脑铝水平明显高于对照组(P<0.05)。免疫印迹法结果显示,小鼠脑组织总tau蛋白及tau蛋白在Thr181、Thr231、Ser262和Ser396位点的磷酸化表达,高、中、低剂量组明显高于对照组(P<0.05)。 结论 铝暴露可导致小鼠认知功能障碍及tau蛋白过度磷酸化,这可能是铝致小鼠认知功能障碍的机制之一。 Abstract:Objective To explore the effect of chronic aluminum exposure on learning and memory and the phosphorylation levels of tau protein in mice. Methods Three groups of mice were fed with AlCl3 at 120.0, 12.0 and 1.2 mg/(kg& #183;d) respectively for 1 year, and one control group with normal diet. Spatial learning and memory ability were tested with Morris water maze (MWM). Brain aluminum content was determined by inductively coupled plasma mass spectrometry (ICP-MS). The expression of total tau and phosphorylated tau in Thr181, Thr231, Ser262 and Ser396 sites in brain tissues of mice were detected by Western blot. Results Compared with the control group, the MWM latent period of high and middle dose groups was significantly prolonged (P<0.05); the number of traversing platform in high and middle dose groups were significantly decreased (P<0.05); and brain aluminum levels of all 3 exposure groups were significantly higher (P<0.05). Western blot test demonstrated that the total tau and the phosphorylation levels in Thr181, Thr231, Ser262 and Ser396 sites of all 3 exposure groups were significantly higher than those of the control group (P<0.05). Conclusion Aluminum exposure can lead to cognitive dysfunction in mice and the overphosphorylation of tau protein, which may be one of the mechanisms of cognitive dysfunction induced by aluminum.
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