SIRT1调节突触蛋白Synapsin 1表达和神经元树突生长  

SIRT1 Regulates the Expression of Synapsin 1 and the Growth of Neuron Dendrites

作　　者：顾群 黄琴 徐子淇 吴凡 尹晓敏[1] 张旭[2] 钱慰[1] GU Qun;HUANG Qin;XU Zi-Qi;WU Fan;YIN Xiao-Min;ZHANG Xu;QIAN Wei(Department of Biochemistry and Molecular Biology,Nantong University School of Medicine,Jiangsu Key Laboratory of Neurodegeneration,Co-innovation Center of Neurodegeneration,Nantong 226001,Jiangsu,China;Central Laboratory,Xuanwu Hospital,Capital Medical University,Beijing Geriatric Medical Research Center,Beijing Institute for Brain Disorders,Beijing 100053,China)

机构地区：[1]南通大学医学院生物化学与分子生物学系,江苏省神经再生重点实验室,江苏省神经再生协同创新中心,江苏南通226001 [2]首都医科大学宣武医院中心实验室,北京市老年病医疗研究中心,北京脑重大疾病研究院阿尔茨海默病研究所,北京100053

出　　处：《中国生物化学与分子生物学报》2020年第11期1353-1358,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.81872875,81473218,81170317);江苏省高校优势学科建设项目(PAPD);江苏省大学生创新训练计划项目(No.201910304105Y)资助。

摘　　要：阿尔茨海默病(Alzheimer’s disease,AD)早期就出现突触功能紊乱。沉默调节蛋白1(silent information regulator 1,SIRT1)是与AD相关的重要去乙酰化酶。本研究探讨了SIRT1对突触蛋白1(synapsin 1)表达和对神经元树突生长的影响。Western印迹检测结果显示,SIRT1显著抑制小鼠神经瘤母细胞系N2a细胞和海马神经元细胞内突触蛋白1的蛋白质表达(P<0.01)。而自噬溶酶体降解途径抑制剂(3-Methyladenine,3-MA)处理可使突触蛋白1的蛋白质表达水平显著上升(P<0.01),说明其抑制作用可能与突触蛋白1的自噬溶酶体途径降解有关。利用免疫荧光检测SIRT1活化剂白藜芦醇(resveratrol,RSV)对神经元树突生长的影响,发现RSV可促进海马神经元树突生长,并抑制其分支生成。SIRT1^+/-杂合子小鼠脑内突触蛋白1的蛋白质表达较之正常组显著增高(P<0.05),树突棘密度显著增加(P<0.05)。综上所述,SIRT1可抑制突触蛋白1表达并且调节神经元树突的生长。Synaptic dysfunction occurs early in Alzheimer’s disease(AD).Silent information regulator 1(SIRT1)is an important AD-associated deacetylase.This study aims to explore the effect of SIRT1 on the expression of synapsin 1 and the growth of neuron dendrites.We found SIRT1 inhibited the protein expression of synapsin 1 significantly in N2 a cell lines and hippocampal neurons by Western blots(P<0.01).However,3-methyladenine(3-MA)treatment significantly increased the protein expression level of synapsin 1(P<0.01),suggesting that the regulation of synapsin 1 by SIRT1 may be related to the autophagic lysosomal pathway.The role of SIRT1 activator resveratrol(RSV)on the dendritic growth of hippocampal neurons was detected by immunofluorescence.The protein expression level of synapsin 1 in SIRT1^+/-mice was significantly higher than that in normal mice(P<0.05),and the density of dendritic spines was significantly increased(P<0.05).In conclusion,SIRT1 can inhibit the expression of synapsin 1 and regulate the growth of neuronal dendrites.

关 键 词：阿尔茨海默病 沉默调节蛋白1 突触蛋白1 神经元树突 

分 类 号：Q189[生物学—神经生物学]