Vasoactive Intestinal Peptide Is Critical for Circadian Regulation of Glucocorticoids

Vasoactive Intestinal Peptide Is Critical for Circadian Regulation of Glucocorticoids
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DOI:
10.1159/000140676
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发表时间:
2008-01-01
期刊:
影响因子:
4.1
通讯作者:
Waschek, James A.
Waschek, James A.
中科院分区:
医学2区
文献类型:
--
作者:
Loh, Dawn H.;Abad, Catalina;Waschek, James A.

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背景/目的:行为和生理的昼夜节律控制是所有生物体的中心特征。哺乳动物的主时钟位于下丘脑,视交叉上核(SCN)负责维持日常节奏。最近的各种证据表明,神经肽血管活性肠肽(VIP)对SCN的正常功能至关重要。本研究的目的是探讨VIP在驱动下丘脑-垂体-肾上腺轴昼夜节律中的可能作用。方法:在昼夜和昼夜条件下,通过全天候采样测定循环ACTH和皮质酮浓度。下丘脑-垂体-肾上腺轴的反应方面进行了测试的应用程序的急性应激足电击和光。结果:我们证明了在VIP缺陷小鼠中ACTH和皮质酮的昼夜节律丢失。在突变小鼠中,光诱导皮质酮反应的能力也受到损害,肾上腺中Per 1的光诱导也受到损害。与此相反,急性应激反应显然是不变的损失的VIP。结论:因此,我们的数据表明,VIP是必不可少的昼夜节律调节,否则完整的下丘脑-垂体-肾上腺轴。版权所有(C)2008 S. Karger AG,巴塞尔
Background/Aims: Circadian control of behavior and physiology is a central characteristic of all living organisms. The master clock in mammals resides in the hypothalamus, where the suprachiasmatic nucleus (SCN) synchronizes daily rhythms. A variety of recent evidence indicates that the neuropeptide vasoactive intestinal peptide (VIP) is critical for normal functioning of the SCN. The aim of our study was to examine the possible role of VIP in driving circadian rhythms in the hypothalamic-pituitary-adrenal axis. Methods: Circulating ACTH and corticosterone concentrations were determined by round-the-clock sampling under diurnal and circadian conditions. The responsive aspects of the hypothalamic-pituitary-adrenal axis were tested by application of acute stress by footshock and light. Results: We demonstrate that the circadian rhythms in ACTH and corticosterone are lost in VIP-deficient mice. The ability of light to induce a corticosterone response was also compromised in the mutant mice, as was photic induction of Per1 in the adrenal glands. In contrast, the acute stress response was apparently unaltered by the loss of VIP. Conclusion: Thus, our data demonstrate that VIP is essential for the circadian regulation of an otherwise intact hypothalamic-pituitary-adrenal axis. Copyright (C) 2008 S. Karger AG, Basel