A bidirectional relationship between sleep and oxidative stress in Drosophila.
A bidirectional relationship between sleep and oxidative stress in Drosophila.
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DOI：
10.1371/journal.pbio.2005206
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发表时间：
2018-07
期刊：
影响因子：
9.8
通讯作者：
Shirasu-Hiza M
中科院分区：
文献类型：
--
作者：
Hill VM;O'Connor RM;Sissoko GB;Irobunda IS;Leong S;Canman JC;Stavropoulos N;Shirasu-Hiza M
尽管睡眠在动物中似乎广泛存在，但睡眠的生理功能仍不清楚。在这项研究中，我们试图找出不同群体的短睡眠果蝇突变体中常见的生理缺陷，这可能有助于深入了解睡眠的功能和调节。我们发现这些短睡眠突变体具有对急性氧化应激敏感的共同表型，表现出比对照更短的生存时间。我们进一步表明，使用遗传或药理学方法增加野生型果蝇的睡眠可以提高氧化挑战后的存活率。此外，通过抗氧化基因的过度表达来减少野生型果蝇神经元中的氧化应激，从而减少睡眠时间。总之，这些结果支持了这样的假设：睡眠的一个关键功能是抵御氧化应激，并且还指出神经元中活性氧 (ROS) 在睡眠调节中的相互作用。大多数动物都在睡觉；人类一生中近三分之一的时间都在睡觉。然而睡眠的基本功能仍然未知。在这里，我们使用短睡眠果蝇突变体来揭示睡眠在抵抗氧化应激中的作用。氧化应激是活性氧和抗氧化反应的不平衡。尽管这些短睡眠突变体在多种途径上存在缺陷，但它们都表现出对氧化应激的敏感性。此外，增加野生型果蝇的睡眠可以增强对氧化应激的抵抗力。这表明睡眠的一项功能是抵御氧化应激。最后，减少野生型果蝇神经元的氧化应激会减少它们的睡眠，这表明氧化应激也调节睡眠。总而言之，我们的结果支持了睡眠和氧化应激之间双向关系的一个有趣的假设：氧化应激触发睡眠，然后睡眠充当身体和大脑的抗氧化剂。这些结果对患有慢性睡眠限制和与氧化应激相关疾病的人类患者具有影响。
Although sleep appears to be broadly conserved in animals, the physiological functions of sleep remain unclear. In this study, we sought to identify a physiological defect common to a diverse group of short-sleeping Drosophila mutants, which might provide insight into the function and regulation of sleep. We found that these short-sleeping mutants share a common phenotype of sensitivity to acute oxidative stress, exhibiting shorter survival times than controls. We further showed that increasing sleep in wild-type flies using genetic or pharmacological approaches increases survival after oxidative challenge. Moreover, reducing oxidative stress in the neurons of wild-type flies by overexpression of antioxidant genes reduces the amount of sleep. Together, these results support the hypothesis that a key function of sleep is to defend against oxidative stress and also point to a reciprocal role for reactive oxygen species (ROS) in neurons in the regulation of sleep. Most animals sleep; humans sleep nearly a third of their lives. Yet the fundamental functions of sleep remain unknown. Here, we used short-sleeping Drosophila mutants to uncover a role for sleep in resistance to oxidative stress. Oxidative stress is an imbalance of reactive oxygen species and antioxidant responses. Although these short-sleeping mutants have defects in diverse pathways, they all exhibit sensitivity to oxidative stress. Moreover, increasing sleep in wild-type flies increased resistance to oxidative stress. This suggests that one function of sleep is to defend against oxidative stress. Finally, reducing oxidative stress in neurons of wild-type flies reduces their sleep, suggesting that oxidative stress also regulates sleep. Taken together, our results support an intriguing hypothesis for a bidirectional relationship between sleep and oxidative stress: oxidative stress triggers sleep, which then acts as an antioxidant for both the body and the brain. These results have implications for human patients suffering from chronic sleep restriction and diseases associated with oxidative stress.
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