Hypoactivity of the hypothalamo-pituitary-adrenocortical axis during recovery from chronic variable stress
Hypoactivity of the hypothalamo-pituitary-adrenocortical axis during recovery from chronic variable stress
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DOI：
10.1210/en.2005-1041
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发表时间：
2006-04-01
期刊：
影响因子：
4.8
通讯作者：
Herman, JP
中科院分区：
文献类型：
--
作者：
Ostrander, MM;Ulrich-Lai, YM;Herman, JP
慢性应激诱导下丘脑-垂体-肾上腺皮质（HPA）轴内的功能和结构适应，提示神经内分泌对后续应激反应的长期改变。我们假设，以前的慢性应激会产生持续增强HPA轴的反应性新的压力。成年雄性大鼠暴露于慢性可变应激（CVS）1周，并允许恢复。血浆ACTH和皮质酮水平测定对照组或CVS大鼠暴露于新的心因性（新的环境或约束）或全身性（缺氧）应激源在16小时，4天，7天，或30天后CVS停止。血浆促肾上腺皮质激素和皮质酮反应的心因性应激源衰减4 d（新的环境和约束）和7 d（新的环境只）恢复CVS，而激素反应的全身性应激源在很大程度上不受CVS。CVS停止后16 h，下丘脑室旁核CRH mRNA表达上调，但下丘脑室旁核CRH和精氨酸加压素mRNA表达无明显变化。因此，与我们的假设相反，降低HPA轴敏感性心因性应激表现在CVS后延迟恢复时间点。HPA轴的能力，以响应系统的压力出现在很大程度上完整的CVS恢复过程中。这些数据表明，慢性应激选择性地靶向负责整合心因性刺激的脑回路，导致HPA轴反应性降低，可能部分由PVN CRH表达的短暂改变介导。
Chronic stress induces both functional and structural adaptations within the hypothalamo-pituitary-adrenocortical (HPA) axis, suggestive of long-term alterations in neuroendocrine reactivity to subsequent stressors. We hypothesized that prior chronic stress would produce persistent enhancement of HPA axis reactivity to novel stressors. Adult male rats were exposed to chronic variable stress (CVS) for 1 wk and allowed to recover. Plasma ACTH and corticosterone levels were measured in control or CVS rats exposed to novel psychogenic (novel environment or restraint) or systemic (hypoxia) stressors at 16 h, 4 d, 7 d, or 30 d after CVS cessation. Plasma ACTH and corticosterone responses to psychogenic stressors were attenuated at 4 d (novel environment and restraint) and 7 d (novel environment only) recovery from CVS, whereas hormonal responses to the systemic stressor were largely unaffected by CVS. CRH mRNA expression was up-regulated in the paraventricular nucleus of the hypothalamus (PVN) at 16 h after cessation of CVS, but no other alterations in PVN CRH or arginine vasopressin mRNA expression were observed. Thus, in contrast to our hypothesis, reductions of HPA axis sensitivity to psychogenic stressors manifested at delayed recovery time points after CVS. The capacity of the HPA axis to respond to a systemic stressor appeared largely intact during recovery from CVS. These data suggest that chronic stress selectively targets brain circuits responsible for integration of psychogenic stimuli, resulting in decreased HPA axis responsiveness, possibly mediated in part by transitory alterations in PVN CRH expression.