Insulin-Like Growth Factor I Modulates Sleep Through Hypothalamic Orexin Neurons

Although metabolic and sleep disturbances are commonly associated, the underlying processes are not yet fully defined. Insulin-like growth factor-I (IGF-I), an anabolic hormone that shows a circadian pattern in the circulation and activity-dependent entrance in the brain, is associated to sleep regulation along evolution. However, its role in this universal homeostatic process remains poorly understood. We now report that the activity of orexin neurons, a discrete cell population in the lateral hypothalamus that is involved in the circadian sleep/wake cycle and arousal, is modulated by circulating IGF-I. Furthermore, mice with blunted IGF-I receptor activity in orexin neurons have lower levels of orexin in the hypothalamus, show altered electrocorticographic patterns with predominant slow wave activity, reduced onset-sleep latency, and less transitions between sleep and awake stages. Collectively, these results extend the role of this pleiotropic growth factor to shaping sleep architecture through regulation of orexin neurons. We speculate that poor sleep quality associated to diverse conditions may be related to disturbed brain IGF-I input to orexin neurons.