MEF2C ameliorates learning,memory,and molecular pathological changes in Alzheimer’s disease in vivo andin vitro  

作　　者：Jiamou Ren Shuli Zhang Xiaoling Wang Yuxin Deng Yi Zhao Yan Xiao Jian Liu Liangzhao Chu Xiaolan Qi 

机构地区：[1]Key Laboratory of Endemic and Ethnic Diseases,Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou Province,Guizhou Medical University,Guiyang 550004,China [2]Department of Laboratory Medicine,the 4th People′s Hospital of Guiyang,Guiyang 550004,China [3]Translational Medicine Research Center,Guizhou Medical University,Guiyang 550004,China [4]Department of Neurosurgery,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China [5]Chinese People′s Liberation Army,Secret Service Center Sanatorium of Xiamen,Xiamen 361000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第1期77-90,共14页生物化学与生物物理学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(No.81860207);the Program for Changjiang Scholars and Innovative Research Team in University(No.IRT13058);the Guizhou Science and Technology Foundation(Nos.[2019]1437 and[2017]1149);the Department of Education of Guizhou Province(No.KY[2021]313 and YJSCXJH(2020)145).

摘　　要：Myocyte enhancer factor 2C(MEF2C)is highly expressed in the nervous system,and regulates neuro-development,synaptic plasticity,and inflammation.However,its mechanism in Alzheimer’s disease(AD)is underestimated.In this study,the role and mechanism of MEF2C were investigated in the brain tissue specimens from patients with AD,APPswe/PSEN1dE9 double transgenic(APP/PS1_DT)mice,and SH-SY5Y cells treated withβ-amyloid peptide(Aβ).The results indicated that the expression of MEF2C is significantly reduced,and the expression of MEF2C/Aβin different parts of brain is negatively correlated in patients with AD.Knockdown of MEF2C promotes cell apoptosis and the level ofβ-amyloid precursor protein cleaving enzyme 1(BACE)but reduces BACE2 expression.In addition,knockdown of Mef2c enhances the generation and aggregation of Aβin the cortex of APP/PS1_DT mice,reduces the expression of synaptic proteins,exacerbates the ability of learning and memory of APP/PS1_DT mice,damages the structure of mitochondria,increases the oxidative stress(OS)level,and inhibits the expression levels of members of the Nrf2-ARE signal pathway.In summary,inhibition of MEF2C exacerbates the toxic effect of Aβin vivo and in vitro,damages synaptic plasticity,reduces the ability of learning and memory of APP/PS1 mice,and increases the level of OS via the Nrf2-ARE signal pathway.

关 键 词：myocyte enhancer factor 2C(MEF2C) Alzheimer’s disease APPswe/PSEN1dE9 double transgenic mice oxidative stress Nrf2-ARE 

分 类 号：R749.16[医药卫生—神经病学与精神病学]