Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
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DOI：
10.1038/s41467-021-22179-z
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发表时间：
2021-04-09
影响因子：
16.6
通讯作者：
Vasudevan SR
中科院分区：
文献类型：
--
作者：
Jagannath A;Varga N;Dallmann R;Rando G;Gosselin P;Ebrahimjee F;Taylor L;Mosneagu D;Stefaniak J;Walsh S;Palumaa T;Di Pretoro S;Sanghani H;Wakaf Z;Churchill GC;Galione A;Peirson SN;Boison D;Brown SA;Foster RG;Vasudevan SR
腺苷的积累与睡眠需求密切相关，咖啡因会拮抗睡眠压力的检测。咖啡因也会直接影响昼夜节律计时系统，并且独立于睡眠生理学，但咖啡因如何介导这些对昼夜节律钟的影响尚不清楚。在这里，我们确定了一种基于腺苷的调节机制，允许睡眠和昼夜节律过程相互作用，以优化小鼠的睡眠/觉醒时间。腺苷编码睡眠历史，并且该信号通过光调节昼夜节律夹带。药理学和遗传学方法表明，腺苷通过腺苷A1/A2 A受体信号传导作用于昼夜节律时钟，腺苷A1/A2 A受体信号传导通过激活Ca 2 + -ERK-AP-1和CREB/CRTC 1-CRE途径来调节时钟基因Per 1和Per 2。我们表明，这些信号通路会聚在一起，并抑制光激活的相同途径。因此，昼夜节律夹带由光系统地调制在每天的基础上的睡眠历史。这些发现有助于我们理解腺苷如何整合来自光和睡眠的信号来调节小鼠的昼夜节律。睡眠压力和昼夜节律相互影响。然而，监管机制尚不明确。在这里，作者表明，腺苷A1/A2 A受体拮抗剂，如咖啡因，改变昼夜节律，增强光的作用，提供了睡眠压力和昼夜节律之间的分子联系。
The accumulation of adenosine is strongly correlated with the need for sleep and the detection of sleep pressure is antagonised by caffeine. Caffeine also affects the circadian timing system directly and independently of sleep physiology, but how caffeine mediates these effects upon the circadian clock is unclear. Here we identify an adenosine-based regulatory mechanism that allows sleep and circadian processes to interact for the optimisation of sleep/wake timing in mice. Adenosine encodes sleep history and this signal modulates circadian entrainment by light. Pharmacological and genetic approaches demonstrate that adenosine acts upon the circadian clockwork via adenosine A1/A2A receptor signalling through the activation of the Ca2+ -ERK-AP-1 and CREB/CRTC1-CRE pathways to regulate the clock genes Per1 and Per2. We show that these signalling pathways converge upon and inhibit the same pathways activated by light. Thus, circadian entrainment by light is systematically modulated on a daily basis by sleep history. These findings contribute to our understanding of how adenosine integrates signalling from both light and sleep to regulate circadian timing in mice. Sleep pressure and circadian rhythms influence one another. However, the regulatory mechanisms are unclear. Here, the authors show that adenosine A1/A2A receptor antagonists, such as caffeine, shift circadian rhythms and enhance the effects of light, providing a molecular link between sleep pressure and circadian rhythm.
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影响因子：
5.7
作者：
Greene RW;Bjorness TE;Suzuki A
通讯作者：
Suzuki A
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5.3
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