Primate Early Life Stress Leads to Long-Term Mild Hippocampal Decreases in Corticosteroid Receptor Expression
Primate Early Life Stress Leads to Long-Term Mild Hippocampal Decreases in Corticosteroid Receptor Expression
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DOI：
10.1016/j.biopsych.2009.12.016
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发表时间：
2010-06-01
影响因子：
10.6
通讯作者：
Pryce, Christopher R.
中科院分区：
文献类型：
--
作者：
Arabadzisz, Dimitrula;Diaz-Heijtz, Rochellys;Pryce, Christopher R.
背景资料：盐皮质激素受体（MR）和糖皮质激素受体（GR）基因的表达在抑郁症的几个脑区适度减少。这些减少可能部分是由于早期生活压力（ELS），这预示着情绪障碍。控制灵长类动物的研究是很重要的，以测试是否ELS足以诱导长期的情绪变化也会导致长期改变MR和/或GR的大脑expression.Methods：在普通的绒猴，ELS的日常30-120分钟的社会隔离在一个月-1导致一些长期的变化，在稳态和情绪行为。在这些相同的受试者中，本研究的目的是使用绒猴特异性核糖核酸探针来确定ELS是否对脑MR和GR基因表达产生长期影响。在青春期，相对于对照组，ELS绒猴表现出轻度减少的信使RNA信号，（-15%，p = 0.05）和GR（-13%，p = 0.02）在海马-主要是CA 1-但不是在前额叶皮质，其他皮质区域，或下丘脑.结论：在青春期绒猴脑，减少海马MR和GR的表达是一致的慢性指标ELS.这些慢性、轻度、特定的减少不太可能是观察到的ELS长期情绪影响的急性介导剂。然而，他们确实表明海马MR/GR参与ELS的神经发育效应。
Background: 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.Methods: 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.Results: 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-but not in prefrontal cortex, other cortical regions, or hypothalamus.Conclusions: 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.