Corticosterone administration up-regulated expression of norepinephrine transporter and dopamine β-hydroxylase in rat locus coeruleus and its terminal regions.
Corticosterone administration up-regulated expression of norepinephrine transporter and dopamine β-hydroxylase in rat locus coeruleus and its terminal regions.
复制标题
DOI：
10.1111/jnc.12459
复制
发表时间：
2014-02
影响因子：
4.7
通讯作者：
Zhu MY
中科院分区：
文献类型：
--
作者：
Fan Y;Chen P;Li Y;Cui K;Noel DM;Cummins ED;Peterson DJ;Brown RW;Zhu MY
据报道，应激可激活蓝斑（LC）-去甲肾上腺素能系统。在本研究中，皮质酮（CORT）口服给药大鼠21天，以模拟应激状态。原位杂交结果表明，CORT摄入显著增加了LC区去甲肾上腺素转运体（NET）和多巴胺β-羟化酶（DBH）的mRNA水平。免疫荧光染色和蛋白质印迹显示，CORT治疗也增加了NET和DBH的蛋白质水平在LC，以及NET蛋白质水平在海马，额叶皮质和杏仁核。然而，CORT诱导的DBH蛋白水平的增加只出现在海马和杏仁核。在大多数这些区域中升高的NET和DBH表达（LC中的NET蛋白水平除外）通过同时用皮质类固醇受体拮抗剂米非司酮和螺内酯（s.c. 21天）。此外，单独使用米非司酮治疗可防止皮质醇诱导的LC中NET表达和DBH蛋白水平的增加。此外，行为任务表明，CORT摄入促进逃避回避试验中使用高架T-迷宫，但有趣的是，有没有对逃避试验的显着影响。皮质类固醇受体拮抗剂未能抵消CORT治疗大鼠的这种反应。在旷场任务中，与对照组相比，CORT治疗导致定义的中心区域的活动减少，皮质类固醇受体拮抗剂治疗缓解了这种增加。总之，本研究表明，慢性暴露于CORT的结果在表型，模仿应激诱导的去甲肾上腺素能表型的改变，但对行为的影响是任务依赖性的。由于蔗糖消耗试验强烈表明CORT摄入诱导的抑郁样行为，进一步阐明潜在的机制可能会提高我们对压力和抑郁症的发展之间的相关性的理解。
Stress has been reported to activate the locus coeruleus (LC)–noradrenergic system. In the present study, corticosterone (CORT) was orally administrated to rats for 21 days to mimic stress status. In situ hybridization measurements showed that CORT ingestion significantly increased mRNA levels of norepinephrine transporter (NET) and dopamine β-hydroxylase (DBH) in the LC region. Immunofluorescence staining and western blotting revealed that CORT treatment also increased protein levels of NET and DBH in the LC, as well as NET protein levels in the hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase of DBH protein levels only appeared in the hippocampus and the amygdala. Elevated NET and DBH expression in most of these areas (except for NET protein levels in the LC) was abolished by simultaneous treatment with combination of corticosteroid receptor antagonist mifepristone and spironolactone (s.c. for 21 days). Also, treatment with mifepristone alone prevented CORT-induced increases of NET expression and DBH protein levels in the LC. In addition, behavioral tasks showed that CORT ingestion facilitated escape in avoidance trials using an elevated T-maze, but interestingly, there was no significant effect on the escape trial. Corticosteroid receptor antagonists failed to counteract this response in CORT-treated rats. In the open-field task, CORT treatment resulted in less activity in a defined central zone compared to controls and corticosteroid receptor antagonist treatment alleviated this increase. In conclusion, the present study demonstrates that chronic exposure to CORT results in a phenotype that mimics stress-induced alteration of noradrenergic phenotypes, but the effects on behavior are task-dependent. As the sucrose consumption test strongly suggests CORT ingestion-induced depression-like behavior, further elucidation of underlying mechanisms may improve our understanding of the correlation between stress and the development of depression.
登录
查看更多内容
影响因子：
--
作者：
Gourley, Shannon L;Taylor, Jane R
通讯作者：
Taylor, Jane R
影响因子：
5
作者：
DeVries, J;Schoffelmeer, ANM;Vanderschuren, LJMJ
通讯作者：
Vanderschuren, LJMJ
影响因子：
4.8
作者：
AHIMA, RS;HARLAN, RE
通讯作者：
HARLAN, RE
DOI：
10.1037/h0077603
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
ANISMAN, H;SKLAR, LS
通讯作者：
SKLAR, LS
影响因子：
4.1
作者：
Jadavji, Nafisa M.;Supina, Rebecca D.;Metz, Gerlinde A.
通讯作者：
Metz, Gerlinde A.