Decreased expression of mineralocorticoid receptor mRNA and its splice variants in postmortem brain regions of patients with major depressive disorder
Decreased expression of mineralocorticoid receptor mRNA and its splice variants in postmortem brain regions of patients with major depressive disorder
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DOI：
10.1016/j.jpsychires.2010.12.002
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发表时间：
2011-07-01
影响因子：
4.8
通讯作者：
DeRijk, Roel H.
中科院分区：
文献类型：
--
作者：
Klok, Melanie D.;Alt, Simone R.;DeRijk, Roel H.
大脑中糖皮质激素受体（GR）和矿皮质激素受体（MR）的适当信号传导对调节下丘脑-垂体-肾上腺（HPA）轴、情绪唤醒和认知表现至关重要。迄今为止，关于重度抑郁症（MDD）患者大脑中MR（和GR）表达的数据很少。在定量PCR的帮助下，我们评估了海马、杏仁核、额下回、扣带回和伏隔核组织样本中MR和GR mRNA的表达，包括剪接变体MR α和MR β。比较了6名重度抑郁症患者和6名非抑郁症患者的组织样本的表达水平。相对于总GR，海马总mRNA表达量较高，杏仁核、额下回和伏隔核表达量较低。在所有被分析的大脑区域都可以检测到MR α和MR β，尽管MR β的表达很低。MDD患者海马、额下回和扣带回组织中MR或GR的表达水平显著降低（30-50%）（p < 0.05），而杏仁核和伏隔核中MR或GR的表达水平无差异。数据显示，MR α和MR β mRNA在整个人类大脑边缘均有表达，其中海马表达量最高。MDD患者特定脑区皮质类固醇受体表达的减少可能是HPA过度活跃、情绪和认知障碍的基础，通常在患有压力相关精神病理的患者中观察到。(C) 2010 Elsevier Ltd.版权所有。
Appropriate signaling in the brain by the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) is critical in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, emotional arousal and cognitive performance. To date, few data exist on MR (and GR) expression in the brain of patients suffering from major depressive disorder (MDD).With the help of quantitative PCR we assessed MR and GR mRNA expression, including the splice variants MR alpha and MR beta, in tissue samples from the hippocampus, amygdala, inferior frontal gyrus, cingulate gyrus and nucleus accumbens. Expression levels were compared between tissue samples from six MDD patients and six non-depressed subjects.Relative to total GR, total MR mRNA expression was higher in hippocampus and lower in the amygdala, inferior frontal gyrus and nucleus accumbens. Both MR alpha and MR beta could be detected in all brain regions that were analyzed, although MR beta expression was low. Significantly lower expression levels (30-50%) were detected for MR or GR in hippocampal, inferior frontal gyrus and cingulate gyrus tissue from MDD patients (p < .05), while no differences were found in the amygdala or nucleus accumbens.The data show that both MR alpha and MR beta mRNA are expressed throughout the human limbic brain with highest expressions in the hippocampus. A decreased expression of corticosteroid receptors in specific brain regions of MDD patients could underlie HPA hyperactivity, mood and cognitive disturbances often observed in patients suffering from stress-related psychopathologies. (C) 2010 Elsevier Ltd. All rights reserved.