CTNND2基因敲除对小鼠学习记忆的影响  

Effects of CTNND2 knockout in mice on learning and memory

作　　者：徐蔓 王潇娅 王路义 邓静 王岩[1] 李英博[1] 王莎莉[1] Xu Man;Wang Xiaoya;Wang Luyi;Deng Jing;Wang Yan;Li Yingbo;Wang Shali(Center of Neuroscience,College of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学基础医学院神经科学研究中心,重庆400016

出　　处：《神经解剖学杂志》2021年第2期189-195,共7页Chinese Journal of Neuroanatomy

基　　金：重庆市基础研究与前沿探索项目(CSTC2018jcyjAX0646)。

摘　　要：目的:探讨连环蛋白δ2(CTNND2)基因敲除对小鼠学习记忆功能的影响及可能机制。方法:聚合酶链式反应(PCR)验证野生型(WT)和CTNND2^(-/-)两组小鼠基因型。Morris水迷宫检测两组小鼠空间学习记忆功能。高尔基染色法检测两组小鼠海马区神经元树突棘密度的变化。Western Blot检测两组小鼠海马突触相关蛋白磷酸化突触素蛋白(P-Syn)、富含谷氨酸/亮氨酸/赖氨酸/丝氨酸蛋白(ELKS)和突触后致密蛋白95(PSD95)的表达水平。结果:与WT小鼠相比,水迷宫实验结果显示CTNND2^(-/-)小鼠逃逸潜伏期明显延长(P<0.05),通过平台的次数显著减少以及停留在目标象限的时间明显缩短(P<0.05),但是游泳速度不变(P>0.05)。高尔基染色结果显示CTNND2^(-/-)小鼠海马区神经元树突棘密度降低(P<0.05)。Western Blot检测结果显示CTNND2^(-/-)小鼠海马区突触相关蛋白p-Syn、ELKS、PSD95表达均下降(P<0.05).结论:CTNND2基因敲除后,可能通过p-Syn、PSD95和ELKS蛋白表达下调阻碍了小鼠海马区神经元树突以及突触发育,诱发其结构和功能障碍,这可能是CTNND2^(-/-)小鼠学习记忆功能损伤的机制之一。Objective:To observe the effects of delta-catenin/NPRAP/neuronjungin(CTNND2)gene deficient in mice on the learning and memory ability and analyze the possible mechanism.Methods:The genotypes were identified by PCR for wild type(WT)and CTNND2 gene knockout(CTNND2^(-/-))mice.Learning and memory ability of mice was tested by Morris water maze.The changes of dendritic spines in the hippocampus were detected by Golgi staining.The expression of p-Syn,ELKS,and PSD95 in hippocampus was detected by Western Blot.Results:Compared with the WT mice,the escape latency of CTNND2^(-/-)mice increased significantly.While the frequency in traversing the platform and time staying in target quadrant reduced(P<0.05).But,there was no significant difference in swimming speed between the two groups(P>0.05).Golgi staining indicated that the density of dendritic spines in the hippocampus of CTNND2^(-/-)mice was reduced(P<0.05).Western Blot showed that the expression levels of synapse associated proteins(p-Syn,ELKS,and PSD95)were decreased in the hippocampus of CTNND2/mice(P<0.05).Conclusion:Deletion of CTNND2 in mice may interfere with the development of dendritic spines and synapses,possibly via the downregulation of p-Syn,PSD-95,and ELKS proteins,thus inducing the structural anomaly and functional disorder.This may be one of the mechanisms of learning and memory impairment in CTNND2 mice.

关 键 词：连环蛋白δ2基因 学习记忆 海马 树突棘 突触 小鼠 

分 类 号：R338[医药卫生—人体生理学]