| Summary: | <p>Sleep is a vital behaviour, and despite spending one third of our lives asleep, we are yet to define its function. A proposed function connects sleep and the build-up of reactive oxygen species (ROS) in the brain, suggesting that sleep is needed as antioxidant defence mechanism. Indeed, ROS accumulation is implicated with prolonged waking, and artificial increase of ROS in the brain can induce sleep in animals. Using the fruit fly Drosophila melanogaster, investigated sleep’s possible role as an antioxidant defence. Acting as a ROS sensor in sleep-promoting dorsal fan-shaped (dFB) neurons is the potassium channel Shaker’s b subunit Hyperkinetic (Hk). Oxidization of its cofactor NADPH causes conformational changes of the channel and thereby modulates dFB neuron activity. dFB neurons could thus act as an early-alert system for rising ROS levels in the brain.</p>
<p>Here, I analysed the sleep pattern, learning and lifespan of short-sleeping Hk mutants, and found severe deficits in learning as well as a drastically shortened lifespan. Learning, additional to sleep duration, was rescued by reinstating Hk into dFB neurons. Lifespan was affected independently of sleep duration, as pan-neuronal Hk expression was required to rescue lifespan.</p>
<p>Introduction of the ROS-limiting alternative oxidase (AOX) into mitochondria of flies affected sleep duration and architecture similarly to Hk mutants. However, learning and lifespan remained unaffected, showing that flies were healthy despite severely shortened sleep duration. Furthermore, AOX expression in Hk mutants rescued learning, suggesting that learning deficits after chronic sleep deprivation are caused by an accumulation of ROS. Lifespan on the other hand seemed to be affected by loss of Hk regardless of sleep state or AOX expression, showing its dependence on functional Hk itself.</p>
<p>Summarizing, ROS plays an important role in the induction and regulation of sleep, and symptoms of chronic sleep deprivation can be counteracted via regulation of ROS production.</p>
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