Sympathetic input modulates, but does not determine, phase of peripheral circadian oscillators

Sympathetic input modulates, but does not determine, phase of peripheral circadian oscillators
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DOI:
10.1152/ajpregu.00498.2007
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发表时间:
2008-07-01
影响因子:
2.8
通讯作者:
Menaker, Michael
Menaker, Michael
中科院分区:
医学3区
文献类型:
--
作者:
Vujovic, Nina;Davidson, Alec J.;Menaker, Michael

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视交叉上核(SCN)中的昼夜节律时钟在生物体内维持着昼夜节律振荡器之间的相位同步。环境光信号缠绕着SCN,但定时的、有限的进餐对几个外围组织来说是一个压倒一切的时间提示。我们提供了一个外周振荡器,即颌下腺的数据,在这个数据中,饮食的时间限制未能影响基因表达。在白天喂养的大鼠中,颌下腺表达时钟基因Perod1(PER1)的节律保持在光周期(在夜间达到峰值)或变得心律不齐。这一结果表明,摄食信号与光周期信号在设定该组织中时钟基因的相位方面竞争较弱。由于颌下腺接受起源于SCN的交感神经支配,SCN将光周期信号传递给其他振荡器,我们试图评估这种神经输入在颌下腺PER1表达的相位控制中的作用。我们交感神经切断了颌下腺的神经,然后让大鼠接受白天限制的喂养。失神经后,所有颌下腺的PER1节律移位180相,进入白天摄食。这些结果支持这样的假设,即外周振荡器可能接收到有助于其卷吸阶段的多个信号。来自SCN的交感传出可以传递光周期信息,而其他外部信号可能通过其他传出或非神经通路到达组织。在一种不正常的、破坏性的养生方式中,比如白天限制进食,这些不同的信号相互竞争。如果一个信号不明显占优势,就可能导致心律失常。消除主导信号(例如,外科交感神经切除术)可能允许次要信号控制时相。
The circadian clock in the suprachiasmatic nucleus ( SCN) maintains phase synchrony among circadian oscillators throughout the organism. Environmental light signals entrain the SCN, but timed, limited meal access acts as an overriding time cue for several peripheral tissues. We present data from a peripheral oscillator, the submaxillary salivary gland, in which temporal restriction of meals fails to entrain gene expression. In day-fed rats, submaxillary gland rhythms in expression of the clock gene Period1 (Per1) stay entrained to the light cycle ( peaking at night) or become arrhythmic. This result suggests that feeding cues compete weakly with light cycle cues to set the phase of clock genes in this tissue. Since the submaxillary glands receive sympathetic innervation originating in the SCN, which relays light cycle cues to other oscillators, we attempted to assess the role of this neural input in phase control of submaxillary Per1 expression. We sympathetically denervated the submaxillary glands before subjecting rats to daytime-restricted feeding. After denervation, Per1 rhythms in all submaxillary glands shifted phase 180 and entrained to daytime feeding. These results support the hypothesis that peripheral oscillators may receive multiple signals contributing to their phase of entrainment. Sympathetic efferents from the SCN can relay light cycle information, while other external cues may reach tissues through other efferents or nonneural pathways. In an abnormal, disruptive regimen such as daytime-restricted feeding, these different signals compete. Arrhythmicity may result if one signal is not clearly dominant. Elimination of the dominant signal ( e. g., surgical sympathectomy) may allow a secondary signal to control phase.