Mclk1基因缺失对小鼠学习记忆的影响及机制

Effects and mechanisms of Mclk1 gene deletion on learning and memory in mice

目的 研究Mclk1基因缺失对小鼠学习记忆的影响,并探讨其可能的作用机制。方法 观察老年Mclk1;和Mclk1;小鼠在Morris水迷宫中的空间学习记忆能力,采用Western blotting和RT-qPCR方法,测定小鼠海马组织中APP、BACE1蛋白含量及mRNA水平,ELISA法检测小鼠海马组织中Aβ的含量。结果 与Mclk1;小鼠比较,Mclk1;小鼠空间学习记忆能力增强,海马内APP蛋白含量及mRNA水平无明显差异,BACE1蛋白含量及mRNA水平明显降低,Mclk1;小鼠海马Aβ;和Aβ;水平低于Mclk1;小鼠。结论 Mclk1基因缺失小鼠BACE1转录水平降低,导致BACE1对APP的裂解作用减弱,海马内Aβ含量减少,可能是其学习记忆能力增强的原因之一。

Objective To research the effects of Mclkl gene deletion on learning and memory in mice and analyze its possible mechanisms.Methods The spatial learning and memory ability of aged Mclk1;and Mclk1;mice in Morris water maze was observed.The protein content and mRNA level of APP and BACE1 in hippocampal tissues of mice were determined by Western blotting and RT-qPCR.The content of Aβ in hippocampal tissues of mice was detected by ELISA.Results Compared with Mclk1;mice,spatial learning and memory ability of Mclk1;mice was enhanced,APP protein content and mRNA level in hippocampus showed no significant difference,BACE1 protein content and mRNA level were significantly decreased.The level of Aβ;and Aβ;in hippocampus of Mclk1;mice were lower than those of Mclk1;mice.Conclusion The reduced transcription level of BACE1 in Mclk1 gene deletion mice resulted in the inhibition of BACE1 shearing effect on APP and the reduction Aβ content in hippocampus,which may be one of the reasons for the enhanced learning and memory ability.