Distribution of the glucocorticoid receptor in the human amygdala; changes in mood disorder patients
Distribution of the glucocorticoid receptor in the human amygdala; changes in mood disorder patients
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DOI：
10.1007/s00429-013-0589-4
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发表时间：
2013-06
影响因子：
3.1
通讯作者：
Qian Wang;E. Verweij;H. Krugers;M. Joëls;M. Joëls;D. Swaab;P. Lucassen
中科院分区：
文献类型：
--
作者：
Qian Wang;E. Verweij;H. Krugers;M. Joëls;M. Joëls;D. Swaab;P. Lucassen
暴露于压力激活下丘脑-垂体-肾上腺（HPA）轴，刺激肾上腺释放糖皮质激素（GC）。这些激素在身体和大脑中发挥许多作用，并与a.o.糖皮质激素受体（GR）在边缘系统中表达，包括海马和杏仁核。下丘脑-垂体-肾上腺轴过度活跃和应激反馈紊乱是抑郁症的共同特征。GR蛋白存在于人类的下丘脑和海马体中，但是对于GR在杏仁核（一种与恐惧和焦虑有关的大脑结构）中的表达，无论是在健康受试者还是在抑郁症患者中，都知之甚少。由于啮齿类动物的慢性应激会影响杏仁核中的GR表达，因此可以预期抑郁症与健康对照组的GR蛋白水平会发生变化。为了验证这一点，我们研究了GR-α蛋白在死后人类杏仁核中的表达，并评估了10名重性或双相抑郁患者和8名非抑郁对照的变化。丰富的GR免疫反应，观察到在人类杏仁核，无论是在神经元和星形胶质细胞，在其不同的解剖亚核具有类似的模式。在抑郁症患者中，GR蛋白水平以及含GR的星形胶质细胞的百分比显著高于双相抑郁症患者或对照组。两者合计，GR蛋白在人类杏仁核中的突出表达表明，该区域可以形成皮质类固醇和应激的重要靶点，而在重度抑郁症中GR表达增加，但不是双相抑郁症，提示可能参与重度抑郁症的病因。
Exposure to stress activates the hypothalamic–pituitary–adrenal (HPA) axis that stimulates glucocorticoid (GC) release from the adrenal. These hormones exert numerous effects in the body and brain and bind to a.o. glucocorticoid receptors (GR) expressed in the limbic system, including the hippocampus and amygdala. Hyperactivity of the HPA axis and disturbed stress feedback are common features in major depression. GR protein is present in the human hypothalamus and hippocampus, but little is known—neither in healthy subjects nor in depressed patients—about GR expression in the amygdala, a brain structure involved in fear and anxiety. Since chronic stress in rodents affects GR expression in the amygdala, altered GR protein level in depressed versus healthy controls can be expected. To test this, we investigated GR-α protein expression in the post-mortem human amygdala and assessed changes in ten major or bipolar depressed patients and eight non-depressed controls. Abundant GR immunoreactivity was observed in the human amygdala, both in neurons and astrocytes, with a similar pattern in its different anatomical subnuclei. In major depression, GR protein level as well as the percentage of GR-containing astrocytes was significantly higher than in bipolar depressed patients or in control subjects. Taken together, the prominent expression of GR protein in the human amygdala indicates that this region can form an important target for corticosteroids and stress, while the increased GR expression in major, but not bipolar, depression suggests possible involvement in the etiology of major depression.