铝对APP/PS1双转基因小鼠认知能力及mGluR1表达的影响
The Effect of Aluminum Chloride on Cognitive Ability of APP/PS1 Double Transgenic Mice and the Expression of mGluR1
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摘要:
目的 对子代 APP/PS1双转基因小鼠进行基因鉴定, 研究铝对小鼠学习记忆及脑组织内代谢性谷氨酸受体 -1(mGluR1)表达的影响。 方法 用 PCR扩增转入基因组 DNA中的 APP基因, 鉴定其基因型; 将鉴定出的子代小鼠随机分为 2组, 即生理盐水组和 5 mg/kg铝暴露组, 每组 8 只; 采用腹腔注射, 连续2个月, 采用① Morris水迷宫试验检测小鼠学习记忆能力的改变; ②用蛋白印迹法(Western blot)和实时荧光定量 PCR法检测脑组织中 mGluR1蛋白和基因的表达水平。 结果 ①鉴定出 APP/PS1双转基因小鼠; ② Morris水迷宫实验结果显示, 染铝组小鼠找到平台的潜伏期较对照组显著增加(P < 0.01); ③ Western blot结果显示染铝组 mGluR1蛋白表达量高于对照组, 差异有统计学意义(P < 0.01); 实时荧光定量 PCR结果显示染铝组 mGluR1基因表达量高于对照组, 差异有统计学意义(P < 0.01)。 结论 铝可致 APP/PS1双转基因小鼠学习和记忆能力障碍, 且与 mGluR1蛋白和基因的表达水平均升高有关。 Abstract:Objective To identify the genotype of the APP/PS1 double transgenic mice, and to investigate the effects of aluminum on spacial learning and memory and the expression of mGluR1 in APP/PS1 double transgenic mice. Methods The APP gene was amplified by PCR(polymerase chain reaction)from the mice genome DNA.The APP/PS1 double transgenic mice were divided into 2 groups at random, i.e. normal saline group and aluminum exposed group(5 mg/kg), with 8 mice in each group. AlCl3 was given to the mice in exposed group by intraperitoneal injection each other day for two months. The learning and memory abilities of mice were tested by the morris water maze test. The expression of mGluR1 was detected by QRT-PCR and Western blot. Results ① The APP/PS1 double transgenic mice were identified. ② The latent period of morris water maze test in the exposed group was significantly increased(P < 0.01)as compared with the control group. ③ The Western-blot demonstrated that mGluR1 expression in protein level was increased after exposed to aluminum(P < 0.01). The QRT-PCR result showed that the expression of mGluR1 mRNA also increased after exposed to aluminum(P < 0.01). Conclusion Aluminum exposure can cause obvious descend of learning and memory ability in the APP/PS1 double transgenic mice.Aluminum is also related with the upwards regulation of mGluR1.
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