Stress-induced glucocorticoid desensitizes adrenoreceptors to gate the neuroendocrine response to somatic stress in male mice.
Stress-induced glucocorticoid desensitizes adrenoreceptors to gate the neuroendocrine response to somatic stress in male mice.
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压力诱导的糖皮质激素使肾上腺受体脱敏，以对雄性小鼠的躯体应激反应构成神经内分泌反应。
DOI：
10.1016/j.celrep.2022.111509
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发表时间：
2022-10-18
期刊：
影响因子：
8.8
通讯作者：
Tasker, Jeffrey G.
中科院分区：
文献类型：
--
作者：
Jiang, Zhiying;Chen, Chun;Weiss, Grant L.;Fu, Xin;Stelly, Claire E.;Sweeten, Brook L. W.;Tirrell, Parker S.;Pursell, India;Stevens, Carly R.;Fisher, Marc O.;Begley, John C.;Harrison, Laura M.;Tasker, Jeffrey G.
下丘脑促肾上腺皮质激素释放激素 (CRH) 神经元的去甲肾上腺素能传入通过 α1 肾上腺素受体激活为下丘脑 - 垂体 - 肾上腺 (HPA) 轴提供主要的兴奋性驱动。去甲肾上腺素能传入神经优先通过躯体压力刺激而不是心理压力刺激来招募。压力诱导的糖皮质激素反馈到下丘脑，对 HPA 轴进行负调节，提供关键的自动调节约束，防止糖皮质激素过度暴露和神经病理学。负反馈机制是否针对应激模式特异性 HPA 激活尚不清楚。在这里，我们描述了雄性小鼠急性应激后 HPA 轴 α1 肾上腺素受体激活的脱敏，这是由糖皮质激素对 CRH 神经元中肾上腺素受体运输的快速调节介导的。糖皮质激素诱导的 α1 受体转运使 HPA 轴对躯体压力源不敏感，但对心理压力源不敏感。我们的研究结果表明，糖皮质激素对 CRH 神经元中肾上腺素信号传导的快速抑制是体细胞应激激活所特有的，并且揭示了一种快速的、应激模式选择性的糖皮质激素负反馈机制。身体和心理压力会激活皮质类固醇的神经内分泌分泌。去甲肾上腺素回路对于神经内分泌对身体压力的反应至关重要，但对心理压力则不然。江等人。研究表明，压力引起的皮质类固醇会降低大脑中去甲肾上腺素的敏感性，从而抑制对随后的身体压力源的反应，但使心理压力反应保持完整。
Noradrenergic afferents to hypothalamic corticotropin releasing hormone (CRH) neurons provide a major excitatory drive to the hypothalamic-pituitary-adrenal (HPA) axis via α1 adrenoreceptor activation. Noradrenergic afferents are recruited preferentially by somatic, rather than psychological, stress stimuli. Stress-induced glucocorticoids feed back onto the hypothalamus to negatively regulate the HPA axis, providing a critical autoregulatory constraint that prevents glucocorticoid overexposure and neuropathology. Whether negative feedback mechanisms target stress modality-specific HPA activation is not known. Here, we describe a desensitization of the α1 adrenoreceptor activation of the HPA axis following acute stress in male mice that is mediated by rapid glucocorticoid regulation of adrenoreceptor trafficking in CRH neurons. Glucocorticoid-induced α1 receptor trafficking desensitizes the HPA axis to a somatic but not a psychological stressor. Our findings demonstrate a rapid glucocorticoid suppression of adrenergic signaling in CRH neurons that is specific to somatic stress activation, and they reveal a rapid, stress modality-selective glucocorticoid negative feedback mechanism. Physical and psychological stressors activate neuroendocrine secretion of corticosteroid. Noradrenaline circuits are critical to the neuroendocrine response to physical but not psychological stress. Jiang et al. show that stress-induced corticosteroids decrease noradrenaline sensitivity in the brain, which suppresses the response to subsequent physical stressors but leaves the psychological stress response intact.
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