Differential regulation of the serotonin 1 A transcriptional modulators five prime repressor element under dual repression-1 and nuclear-deformed epidermal autoregulatory factor by chronic stress.
Differential regulation of the serotonin 1 A transcriptional modulators five prime repressor element under dual repression-1 and nuclear-deformed epidermal autoregulatory factor by chronic stress.
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DOI：
10.1016/j.neuroscience.2009.07.053
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发表时间：
2009-11-10
期刊：
影响因子：
3.3
通讯作者：
Austin, M. C.
中科院分区：
文献类型：
--
作者：
Iyo, A. H.;Kieran, N.;Chandran, A.;Albert, P. R.;Wicks, I.;Bissette, G.;Austin, M. C.
众所周知，慢性压力会影响大脑中涉及学习和情绪反应的区域。这些变化被认为与认知缺陷的发展有关，在严重抑郁障碍(MDD)和其他应激相关的病理生理学中很明显。5-羟色胺相关转录因子(Freud-1/CC2D1A；5个双抑制/卷曲卷曲C2结构域-1A和NUDR/Deaf-1；核变形表皮自身调节因子)是5HT1A受体的两个重要调节因子。应用Western blotting和实时定量聚合酶链式反应(QPCR)检测慢性束缚应激(CRS)雄性大鼠前额叶皮质(PFC)中Freud-1、NUDR和5-HT1a受体的mRNA和蛋白表达。21天后，前额叶皮质Freud-1mRNA和蛋白表达均显著下降(分别为36.8%和32%；p<；0.001)，而NUDR蛋白和蛋白表达水平无明显变化。与降低的弗洛伊德-1蛋白一致，5-HT1A受体的mRNA水平在PFC中同样上调，而蛋白质水平实际上下降，这表明转录后受体下调。这些数据表明，CRS在5-羟色胺系统中产生了明显的改变，特别是改变了雄性大鼠PFC中的弗洛伊德-1和5-HT1a受体，而对NUDR没有影响。这些结果表明，了解弗洛伊德-1和NUDR在PFC中的不同调节机制是重要的，作为理解慢性应激对5-羟色胺系统(5-羟色胺相关转录因子)和应激相关疾病(如抑郁症)的相关影响的基础。
Chronic stress is known to affect brain areas involved in learning and emotional responses. These changes, thought to be related to the development of cognitive deficits are evident in major depressive disorder (MDD) and other stress related pathophysiologies. The serotoninrelated transcription factors ((Freud-1/CC2D1A; five prime repressor element under dual repression/coiled-coil C2 domain-1A and NUDR/Deaf-1; nuclear deformed epidermal autoregulatory factor) are two important regulators of the 5HT1A receptor. Using Western blotting and quantitative real-time polymerase chain reaction (qPCR) we examined the expression of mRNA and proteins for Freud-1, NUDR, and the 5-HT1A receptor in the prefrontal cortex (PFC) of male rats exposed to chronic restraint stress (CRS; 6h/day for 21 days). After 21 days of CRS, significant reductions in both Freud-1 mRNA and protein were observed in the prefrontal cortex (PFC) (36.8% and 32% respectively; p<0.001) while the levels of both NUDR protein and mRNA did not change significantly. Consistent with reduced Freud-1 protein, 5-HT1A receptor mRNA levels were equally upregulated in the PFC, while protein levels actually declined, suggesting post-transcriptional receptor downregulation. The data suggest that CRS produces distinct alterations in the serotonin system specifically altering Freud-1 and the 5-HT1A receptor in the PFC of the male rat while having no effect on NUDR. These results point to the importance of understanding the mechanism for the differential regulation of Freud-1 and NUDR in the PFC as a basis for understanding the related effects of chronic stress on the serotonin system (serotonin-related transcription factors) and stress-related disorders like depression.
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