Abstract

Across animal phyla, sleep is associated with increased cellular repair, suggesting that cellular damage may be a core component of sleep pressure. In support of this notion, sleep in the nematode Caenorhabditis elegans can be triggered by damaging conditions, including noxious heat, high salt, and ultraviolet light exposure. It is not clear, however, whether this stress-induced sleep (SIS) is a direct consequence of cellular damage, or of a resulting energy deficit, or whether it is triggered simply by the sensation of noxious conditions. Here, we show that thermosensation is dispensable for heat-induced sleep, that osmosensation is dispensable for salt-induced sleep, and that wounding is also a sleep trigger, together indicating that SIS is not triggered by sensation of noxious environments. We present evidence that genetic variation in cellular repair pathways impacts sleep amount, and that SIS involves systemic monitoring of cellular damage. We show that the low-energy sensor AMP-activated protein kinase (AMPK) is not required for SIS, suggesting that energy deficit is not the primary sleep trigger. Instead, AMPK-deficient animals display enhanced SIS responses, and pharmacological activation of AMPK reduces SIS, suggesting that ATP-dependent repair of cellular damage mitigates sleep pressure.

摘要

跨动物门，睡眠与细胞修复增加有关，表明细胞损伤可能是睡眠压力的核心组成部分。为了支持这种观点，请在线虫秀丽隐杆线虫中入睡有害的条件（包括有毒的热量，高盐和紫外线照射）可能引发这种情况。然而，尚不清楚这种应激诱导的睡眠（SIS）是细胞损伤的直接结果，还是所导致的能量不足的结果，还是仅仅是由有害条件引起的。在这里，我们表明热感觉对于热诱导的睡眠是必不可少的，渗透压对于盐诱导的睡眠是必不可少的，并且创伤也是睡眠触发，共同表明SIS不是由有害环境的感觉触发的。我们提供的证据表明，细胞修复途径中的遗传变异会影响睡眠量，并且SIS涉及细胞损伤的系统性监测。我们表明，SIS不需要低能量传感器AMP激活的蛋白激酶（AMPK），表明能量不足不是主要的睡眠触发因素。取而代之的是，缺乏AMPK的动物表现出增强的SIS反应，而AMPK的药理激活降低了SIS，表明对细胞损伤的ATP依赖性修复可以缓解睡眠压力。