Vagal regulation of respiratory clocks in mice
Vagal regulation of respiratory clocks in mice
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DOI：
10.1523/jneurosci.4131-06.2007
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发表时间：
2007-04-18
影响因子：
5.3
通讯作者：
Okamura, Hitoshi
中科院分区：
文献类型：
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作者：
Bando, Hideki;Nishio, Takeshi;Okamura, Hitoshi
本研究探讨了昼夜节律系统在小鼠呼吸功能昼夜变化中的作用。在研究的所有气道组织（即喉、气管、支气管和肺）中，我们观察到Per1、Per2、Bmal1和Clock核心振荡器基因（后两个基因与Per基因反相振荡）以及时钟调节的Dbp基因有明显的节律性表达。在Cry1(-/-) Cry2（-/-）敲除小鼠和野生型动物视交叉上核（SCN）主时钟损伤后，振荡被消除。这些发现表明呼吸系统细胞包含一个由SCN控制的功能性外周振荡器。此外，我们发现毒蕈碱乙酰胆碱受体基因Chm2、Chm3和Chm4以昼夜节律方式表达，气道粘膜下腺的粘蛋白分泌（而不是合成）受昼夜节律控制。来自SCN的信号主要通过迷走神经传递，因为单侧迷走神经切断术完全消除了（手术）同侧粘膜下腺的粘蛋白和PER2蛋白水平的节律，但在（完整的）对侧却没有。因此，外周时钟介导的毒蕈碱乙酰胆碱受体蛋白的昼夜节律表达，以及SCN和呼吸组织之间的副交感神经信号传导是将昼夜节律“时间”信息传递给气道腺体的重要途径。
The present study addresses the role of the circadian system in day - night changes of respiratory functions in the mouse. In all airway tissues investigated (i.e., larynx, trachea, bronchus, and lung), we observed clear rhythmic expression of the Per1, Per2, Bmal1, and Clock core oscillator genes ( the latter two genes oscillating in antiphase with the Per genes), as well as the clock-regulated Dbp gene. Oscillations were abolished in arrhythmic Cry1(-/-) Cry2(-/-) knock-out mice and after lesioning of the master clock in the suprachiasmatic nucleus (SCN) in wild-type animals. These findings indicate that respiratory system cells contain a functional peripheral oscillator that is controlled by the SCN. Furthermore, we found that the muscarinic acetylcholine receptor genes Chm2, Chm3, and Chm4 are expressed in a circadian manner, and that mucin secretion ( rather than synthesis) by the airway submucosal glands is under circadian control. Signals from the SCN are mainly transmitted by the vagal nerve because unilateral vagotomy completely abolished rhythms in mucin and PER2 protein levels in the ( operated) ipsilateral side of the submucosal glands, but not in the ( intact) contralateral side. Thus, peripheral clock mediated circadian expression of muscarinic acetylcholine receptor proteins, and parasympathetic signaling between SCN and respiratory tissues are essential gears in conferring circadian "time" information to airway glands.