Chronic psychosocial stress results in sensitization of the HPA axis to acute heterotypic stressors despite a reduction of adrenal in vitro ACTH responsiveness
Chronic psychosocial stress results in sensitization of the HPA axis to acute heterotypic stressors despite a reduction of adrenal in vitro ACTH responsiveness
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DOI：
10.1016/j.psyneuen.2012.02.015
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发表时间：
2012-10
影响因子：
3.7
通讯作者：
Nicole Uschold-Schmidt;Kewir D. Nyuyki;A. Füchsl;I. Neumann;S. Reber
中科院分区：
文献类型：
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作者：
Nicole Uschold-Schmidt;Kewir D. Nyuyki;A. Füchsl;I. Neumann;S. Reber
虽然慢性心理社会应激通常伴随着基础下丘脑-垂体-肾上腺（HPA）轴活动的变化，但当暴露于急性挑战时，慢性应激生物体必须产生足够的糖皮质激素（GC）反应。本研究的主要目的是测试这是否是真的或不为慢性下属殖民地住房（CSC，19天）的范例，建立和临床相关的慢性心理社会应激小鼠模型。如前所述，CSC小鼠的特征在于，尽管肾上腺增大，但早晨血浆皮质酮（CORT）水平未受影响，而晚上血浆CORT水平降低，表明肾上腺功能的适应不良崩溃。通过颈静脉导管重复采血测定的血浆CORT水平以及相对右肾上腺CORT含量在CSC中与单独饲养的对照（SHC）小鼠相比增加，以响应急性升高平台（EPF，5分钟）暴露。然而，在体外刺激肾上腺外植体与生理和药理剂量的促肾上腺皮质激素显示衰减反应的左，右肾上腺CSC后，尽管黑素皮质素2受体（Mc 2 r），Mc 2 r辅助蛋白（MRAP）的mRNA和/或蛋白质表达，类固醇生成的关键酶没有下调。两者合计，我们表明，慢性心理社会应激暴露损害体外ACTH反应的左右肾上腺，而它增加肾上腺反应的急性异型应激体内。这表明，在急性应激暴露在体内抢救左，右肾上腺ACTH敏感性，或本身作为CORT分泌在慢性应激CSC小鼠的额外的因素。
Although chronic psychosocial stress is often accompanied by changes in basal hypothalamo-pituitary-adrenal (HPA) axis activity, it is vital for a chronically-stressed organism to mount adequate glucocorticoid (GC) responses when exposed to acute challenges. The main aim of the present study was to test whether this is true or not for the chronic subordinate colony housing (CSC, 19 days) paradigm, an established and clinically relevant mouse model of chronic psychosocial stress. As shown previously, CSC mice are characterized by unaffected morning and decreased evening plasma corticosterone (CORT) levels despite enlarged adrenals, suggesting a maladaptive breakdown of adrenal functioning. Plasma CORT levels, determined by repeated blood sampling via jugular vein catheters, as well as relative right adrenal CORT content were increased in CSC compared with single-housed control (SHC) mice in response to acute elevated platform (EPF, 5min) exposure. However, in vitro stimulation of adrenal explants with physiological and pharmacological doses of ACTH revealed an attenuated responsiveness of both the left and right adrenal glands following CSC, despite mRNA and/or protein expression of melanocortin 2 receptor (Mc2r), Mc2r accessory protein (MRAP), and key enzymes of steroidogenesis were not down-regulated. Taken together, we show that chronic psychosocial stressor exposure impairs in vitro ACTH responsiveness of both the left and right adrenal glands, whereas it increases adrenal responsiveness to an acute heterotypic stressor in vivo. This suggests that an additional factor present during acute stressor exposure in vivo rescues left and right adrenal ACTH sensitivity, or itself acts as CORT secretagogue in chronically stressed CSC mice.