Department of Psychiatry and Human Behavior, Center for Psychiatric Neuroscience, University of Mississippi Medical Center, School of Medicine, Jackson, MS 39216, USA.
Neuroscience. 2009 Nov 10;163(4):1119-27. doi: 10.1016/j.neuroscience.2009.07.053. Epub 2009 Jul 30.
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 and other stress-related pathophysiologies. The serotonin-related 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 5-HT1A 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; 6 h/day for 21 days). After 21 days of CRS, significant reductions in both Freud-1 mRNA and protein were observed in the 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.
慢性应激已知会影响参与学习和情绪反应的大脑区域。这些变化被认为与认知缺陷的发展有关，在重度抑郁症和其他与应激相关的病理生理学中很明显。与 5-羟色胺相关的转录因子（弗洛伊德-1/CC2D1A；双重抑制下的五端启动子抑制元件/卷曲螺旋 C2 结构域 1a 和 NUDR/Deaf-1；核变形表皮自身调节因子）是 5-HT1A 受体的两个重要调节因子。使用 Western blot 和定量实时聚合酶链反应（qPCR），我们检查了暴露于慢性束缚应激（CRS；每天 6 小时，持续 21 天）的雄性大鼠前额叶皮质（PFC）中 Freud-1、NUDR 和 5-HT1A 受体的 mRNA 和蛋白质表达。在 21 天的 CRS 后，PFC 中 Freud-1 mRNA 和蛋白质水平均显著降低（分别为 36.8%和 32%；P<0.001），而 NUDR 蛋白和 mRNA 水平没有显著变化。与 Freud-1 蛋白减少一致，5-HT1A 受体 mRNA 水平在 PFC 中同样上调，而蛋白质水平实际上下降，表明转录后受体下调。数据表明，CRS 会特异性改变雄性大鼠 PFC 中的 5-羟色胺系统，具体改变 Freud-1 和 5-HT1A 受体，而对 NUDR 没有影响。这些结果表明，了解 Freud-1 和 NUDR 在 PFC 中差异调节的机制非常重要，这是理解慢性应激对 5-羟色胺系统（与 5-羟色胺相关的转录因子）和与应激相关的疾病（如抑郁症）相关影响的基础。
