Notch1信号系统在氟西汀上调大鼠海马神经再生中的作用  

The role of Notch1 signaling in neurogenesis in the rat hippocampus after chronic fluoxetine administration.

作　　者：隋毓秀[1,2] 张志珺[1,2] 郭怡菁[1] 孙奕[1] 

机构地区：[1]东南大学附属中大医院神经内科 [2]南京医科大学附属脑科医院,南京210009

出　　处：《中国神经精神疾病杂志》2011年第5期285-289,共5页Chinese Journal of Nervous and Mental Diseases

基　　金：国家自然科学基金资助项目(编号:30600206,30770779);南京市医学发展项目(编号:YKK10115)

摘　　要：目的了解慢性氟西汀干预正常大鼠所导致的海马神经再生上调与Notch1信号系统功能改变的关系。方法应用大鼠腹腔注射氟西汀建立在体模型,分为对照组、14 d干预组、28 d干预组(n=12),采用免疫组化、real time PCR和Western blot,测定大鼠海马神经干细胞的增殖、存活和分化以及Notch1信号通路各个因子(NICD、Hes1、Hes5、Jag1)的基因及蛋白表达水平的改变。结果①与对照组(2919.50±188.80)比较,14 d氟西汀干预组(3706.50±228.04)、28 d氟西汀干预组(4334.33±217.48)海马齿状回神经干细胞增殖明显增加(P<0.001);与对照组(2404.50±148.77)相比,Flu干预28 d组(3273.16±156.68)海马齿状回神经干细胞存活明显增加(P<0.001);与对照组比较,氟西汀干预组NeuN/BrdU、GFAP/BrdU比例无明显差异(P>0.05)。②与对照组[NICDmRNA(0.30±0.03),Hes1mRNA(0.53±0.03),Hes5mRNA(0.21±0.02),Jag1mRNA(1.04±0.07)]比较,氟西汀(Flu)干预14d组[NICDmRNA(0.45±0.05),Hes1mRNA(0.65±0.06),Hes5mRNA(0.31±0.06),Jag1mRNA(2.46±0.39)]和Flu干预28 d组[NICDmRNA(0.42±0.03),Hes1mRNA(0.85±0.06),Hes5mRNA(0.39±0.02),Jag1mRNA(3.21±0.34)]Notch1信号通路各因子基因水平均明显升高(P<0.01或P<0.001)。③与对照组[NICD(2.36±0.17),Hes1(1.09±0.25),Jag1(2.33±0.31)]比较,Flu干预14 d组[NICD(3.20±0.25),Jag1(2.86±0.25)]和Flu干预28 d组[NICD(3.40±0.19),Hes1(1.43±0.13),Jag1(3.35±0.14)]NICD、Hes1、Jag1蛋白水平明显升高,差异有统计学意义(P<0.01或P<0.001)。与对照组Hes5比较,Flu干预14 d组Hes5和Flu干预28 d Hes5蛋白水平无改变,差异无统计学意义(P>0.05)。结论氟西汀促进大鼠海马齿状回神经干细胞的增殖和存活,但对分化无影响;同时,海马Notch信号功能激活,提示Notch1信号系统可能参与氟西汀介导的大鼠海马神经再生上调。Objective To investigate whether the effect of fluoxetine on hippocampal neurogenesis involves Notch1 signaling.Methods The Notch1 signaling pathway was investigated using real time PCR and Western blot at 14 d and 28 d following fluoxetine administration.Neurogenesis was determined by assessing cell proliferation,survival and differentiation.Results mRNA and protein expression levels of Notch1 signaling components（including Jag1,NICD and Hes1） in the hippocampus increased after fluoxetine administration,accompanied by cell proliferation and survival.The protein expression levels of Hes5 remained unchanged after fluoxetine administration.Conclusions These results indicate that chronic fluoxetine administration activates Notch1 signaling in the hippocampus and the up-regulation of the Notch1 pathway induced by chronic fluoxetine administration might partly contribute to increased neurogenesis in the hippocampus.

关 键 词：氟西汀 神经再生 Notch1信号系统 海马 

分 类 号：R749.4[医药卫生—神经病学与精神病学]