Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology, Zürich, Switzerland.
Biol Psychiatry. 2010 Jun 1;67(11):1106-9. doi: 10.1016/j.biopsych.2009.12.016. Epub 2010 Feb 4.
Expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) genes are moderately reduced in several brain regions in depression. These reductions could be partly due to early life stress (ELS), which predicts emotional disorders. Controlled primate studies are important to test whether ELS sufficient to induce long-term emotional changes also induces long-term altered MR and/or GR brain expression.
In the common marmoset, ELS of daily 30-120-min social isolation across month-1 resulted in some long-term changes in homeostasis and emotional behavior. In some of these same subjects, the aim of this study was to use marmoset-specific riboprobes to determine whether ELS produced long-term effects on brain MR and GR gene expression.
At adolescence, relative to control subjects, ELS marmosets exhibited mildly reduced messenger RNA signal for both MR (-15%, p = .05) and GR (-13%, p = .02) in hippocampus-primarily CA1-2-but not in prefrontal cortex, other cortical regions, or hypothalamus.
In adolescent marmoset monkey brains, reduced hippocampal expression of MR and GR are consistent chronic-indicators of ELS. It is unlikely that these chronic, mild, specific reductions were acute-mediators of the observed long-term emotional effects of ELS. However, they do suggest involvement of hippocampal MR/GR in the neurodevelopmental effects of ELS.
在抑郁症的几个大脑区域中,矿物质皮质激素受体 (MR) 和糖皮质激素受体 (GR) 基因的表达都有中度降低。这些减少可能部分是由于早期生活应激 (ELS),这预示着情绪障碍。受控的灵长类动物研究对于测试 ELS 是否足以引起长期的情绪变化,也是否会引起长期改变的 MR 和/或 GR 脑表达是很重要的。
在普通狨猴中,持续一个月的每天 30-120 分钟的社会隔离 ELS 导致了体内平衡和情绪行为的一些长期变化。在这些相同的研究对象中,本研究的目的是使用狨猴特异性的核糖探针来确定 ELS 是否对大脑 MR 和 GR 基因表达产生了长期影响。
与对照组相比,ELS 狨猴在青春期时,海马体(主要是 CA1-2)中的 MR(-15%,p=0.05)和 GR(-13%,p=0.02)的信使 RNA 信号都有轻微的降低,但在前额叶皮质、其他皮质区域或下丘脑则没有。
在青春期的狨猴大脑中,MR 和 GR 的海马体表达减少是 ELS 的慢性指标。这些慢性、轻度、特异性的减少不太可能是 ELS 观察到的长期情绪影响的急性中介。然而,它们确实表明海马体 MR/GR 参与了 ELS 的神经发育作用。