摘要
为研究慢性温和应激诱导的抑郁大鼠纹状体内前列腺凋亡反应蛋白(prostate apoptosis response-4,par-4)的表达,及甲基化是否参与par-4基因表达的调控,将10周龄大鼠随机分为实验组和对照组,实验组接受慢性温和应激,对照组不接受实验性处理。于大鼠13周龄时,采用强迫游泳、糖水偏爱测验测定大鼠的抑郁水平,以实时定量PCR检测纹状体par-4及多巴胺D2受体(Dopamine receptor D2,DRD2)mRNA表达水平,免疫印迹法检测纹状体par-4蛋白质表达水平,用亚硫酸盐测序法检测par-4基因启动子区甲基化水平。结果发现,与对照组大鼠相比,实验组大鼠漂浮时间延长,糖水偏爱率降低,脑纹状体par-4、DRD2mRNA及par-4蛋白质表达水平均降低,par-4基因启动子区甲基化水平两组差异不显著。提示慢性温和应激诱导大鼠产生了抑郁样行为,并能抑制纹状体par-4基因的表达,而基因甲基化可能并不参与其调控机制。
Chronic stress may induce depression, but the mechanism is unclear. Previous studies suggested that dopamine system, especially dopamine receptor D2 （DRD2） may be involved in, and prostate apoptosis response-4 （par-4） may be the link point between DRD2 and depression. The aims of this research are to detect the expression of par-4 in striatum of a rat model of depression induced by chronic stress, and to explore whether DNA methylaion is involved in the regulatory mechanism of par-4 expression. Newborn rats were randomly divided into two groups, when they grew up to ten weeks, the experimental group rats （n = 17） accepted chronic mild stress for 3 weeks, while the control group rats （n = 17） received no experimental handle. Their depressive level was assessed with forced swimming test and sucrose consumption test; the mRNA expression of par-4 and DRD2 in rats’ striatum was detected by Real-Time PCR; the protein expression of par-4 was detected by western blot; and the DNA methylation level of par-4 was investigated by bisulfated DNA sequencing. The result showed that the float time of experimental rats was longer than the control rats （t = 4.01, p 0.05）, and the sucrose preference rate of experimental rats was reduced compare with the control rats （t = -2.93, p 0.05）. The par-4 and DRD2 mRNA expression of experimental rats were lower than the control rats （t values were -3.56 and -2.507 respectively, p 0.05）, and the fold changes of par-4 and DRD2 mRNA expression in experimental rats compared to control rats were 0.33 and 0.33 respectively. The par-4 protein expression of experimental rats was decreased compared with the control rats （t = -4.92, p 0.05）. However, there was no significant difference between two groups in methylation level of par-4 promoter region （t = -0.26, p 0.05）. These results suggest that chronic mild stress could induce the depressive behaviors of rats and suppress the expression of par-4, but DNA methylation seems to be not involved in the regulatory me
出处
《心理学报》
CSSCI
CSCD
北大核心
2012年第3期330-337,共8页
Acta Psychologica Sinica
基金
国家自然科学基金资助(No.81071097)
