Department of Neurology, Perelman School of Medicine and the Center for Sleep and Circadian Neurobiology, University of Pennsylvania, 462 Stemmler Hall, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Curr Biol. 2013 Mar 18;23(6):501-6. doi: 10.1016/j.cub.2013.02.009. Epub 2013 Mar 7.
Sleep homeostasis, which refers to the maintenance of sleep amount or depth following sleep deprivation, indicates that sleep and sleep-like states serve fundamental functions that cannot be bypassed [1]. Homeostasis of sleep-like behavior is observed during C. elegans lethargus, a 2-3 hr behavioral quiescent period that occurs during larval state transitions [2]. Here, we report a role for DAF-16/FOXO, a transcription factor that is active under conditions of stress [3], in the response to deprivation of lethargus quiescence. Forced locomotion during lethargus results in nuclear translocation of DAF-16. The formation of dauer larvae, a developmental state promoted by daf-16, is increased in response to quiescence deprivation. daf-16 mutants show an impaired homeostatic response to deprivation of lethargus quiescence and are hypersensitive to the lethal effects of forced locomotion during lethargus. DAF-16 expression in muscle cells, but not in neurons, is sufficient to restore a homeostatic response to deprivation of quiescence, pointing to a role for muscle in sleep homeostasis. These findings are relevant to clinical observations of altered metabolic signaling in response to sleep deprivation and suggest that these signaling pathways may act in nonneuronal tissue to regulate sleep behaviors.
睡眠稳态是指在睡眠剥夺后维持睡眠量或深度的能力，它表明睡眠和类似睡眠的状态具有不可替代的基本功能[1]。在秀丽隐杆线虫的休眠行为中观察到类似睡眠行为的稳态，这是一种在幼虫状态转变期间发生的 2-3 小时的行为静止期[2]。在这里，我们报告了 DAF-16/FOXO（一种在应激条件下活跃的转录因子[3]）在响应休眠静止剥夺中的作用。在休眠期间强制运动导致 DAF-16 的核易位。 dauer 幼虫的形成，一种由 daf-16 促进的发育状态，在响应静止剥夺时增加。daf-16 突变体对休眠静止剥夺的稳态反应受损，并且在休眠期间强制运动的致命影响下敏感。肌肉细胞中 DAF-16 的表达，但不是神经元中的表达，足以恢复对静止剥夺的稳态反应，这表明肌肉在睡眠稳态中起作用。这些发现与睡眠剥夺时代谢信号改变的临床观察相关，并表明这些信号通路可能在非神经元组织中发挥作用，以调节睡眠行为。
