尾吊损害大鼠认知功能并下调海马学习记忆相关蛋白表达(英文)  被引量:12

Tail Suspension Disrupts Cognition Function and Down-regulates Memory-related Proteins Expression in Rat Hippocampus

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作  者:陈海龙[1] 吕柯[1] 曲丽娜[1] 张永亮[1] 毕蕾[1] 钟萍[1] 冀国华[1] 曹宏卿[1] 李莹辉[1] 

机构地区:[1]中国航天员科研训练中心,航天医学基础与应用国家重点实验室,中国北京100094

出  处:《航天医学与医学工程》2013年第6期426-432,共7页Space Medicine & Medical Engineering

基  金:Supported by the National Natural Science Foundation of China(30973686);Medicinal Science and Techology Research Project(BWS11J052);the National key scientific instrument and equipment development project(2012YQ0401400901);the National Science and Techology Major Project(2012ZX09J12201);the National Key Technology R&D Program of China(2009BAK59B01);the Foundation of State Key Laboratory of Space Medicine Fundamentals and Application,China Astronaut Research and Training Center(SMFA10B01,SMFA12B05)

摘  要:目的探讨模拟微重力环境对记忆功能和学习相关蛋白表达的影响。方法研究采用7 d尾吊模拟微重力环境,利用水迷宫和跳台检测记忆能力,利用免疫印迹技术检测记忆相关蛋白、神经保护蛋白和抗氧化酶蛋白表达,利用RT-qPCR检测基因表达。结果 SD大鼠尾吊7 d后,空间记忆能力和位置记忆能力均减弱。尾吊降低了大鼠海马学习相关蛋白NR1/2B-CaMKⅡ-CREB通路的活化,机械生长因子MGF及其下游Nrf2介导的神经保护蛋白HO-1表达也明显减少。另外,尾吊抑制了抗氧化酶SOD2和GPx的基因和蛋白表达。这些结果提示,模拟微重力环境明显抑制了海马NR1/2B和MGF信号途径。结论 NR和MGF可能分别作为尾吊介导的认知障碍的调节因子和保护因子,这为微重力环境下认知障碍的学习记忆相关蛋白调节理论奠定了基础。Objective To explore the effects of simulated microgravity on cognitive function and memory-related protein expression. Methods We employed 7 days tail-suspension to simulate microgravity. Behavioral analysis of SD rats was performed with Morris water maze test and step-down test. Expression levels of memory-related proteins, neuroprotective proteins and antioxidases were detected with Western blotting and mRNA expression was measured with RT-qPCR. Results Memory was impaired after simulated microgravity. Tail-suspended rats exhibited decrease in the expression NR1/2B and phosphorylations of CaMK 11 and CREB. Additionally, MGF as well as its downstream Nrf2 mediated neuroprotection of HO-1 was downregulated. Tail-suspension al- so decreased the gene and protein expression of antioxidases such as SOD2 and GPx. Consistent with these findings, NR and MGF signaling in hippocampus displayed significant deficits under weightlessness. Conclu- sion Taken together, these data suggest that NR as well as MGF plays a role of regulator and protective factor of cognitive change respectively induced by microgravity and raise the possibility the dysregulation of memory- related protein may contribute to an array of cognitive disorders under microgravity.

关 键 词:微重力 空间学习 NMDA受体 机械生长因子 

分 类 号:R854[医药卫生—航空、航天与航海医学]

 

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