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

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.