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Insulin‐like growth factor I modulates sleep through hypothalamic orexin neurons
The FASEB Journal ( IF 4.4 ) Pub Date : 2020-10-08 , DOI: 10.1096/fj.202001281rr
Jonathan A. Zegarra‐Valdivia 1, 2, 3 , Jaime Pignatelli 1, 2 , Maria Estrella Fernandez de Sevilla 1, 2 , Ana M. Fernandez 1, 2 , Victor Munive 1, 2 , Laura Martinez‐Rachadell 1, 2 , Angel Nuñez 4 , Ignacio Torres Aleman 1, 2
Affiliation  

Although sleep disturbances are common co‐morbidities of metabolic diseases, the underlying processes linking both are not yet fully defined. Changes in the duration of sleep are paralleled by changes in the levels of 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. However, the specific role, if any, of IGF‐I 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 IGF‐I. Furthermore, mice with blunted IGF‐I receptor activity in orexin neurons have lower levels of orexin in the hypothalamus, show altered electro‐corticographic patterns with predominant slow wave activity, and reduced onset‐sleep latency. Collectively, these results extend the role in the brain of this pleiotropic growth factor to shaping sleep architecture through the 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.

中文翻译:

胰岛素样生长因子 I 通过下丘脑食欲素神经元调节睡眠

尽管睡眠障碍是代谢疾病的常见并发症,但尚未完全确定将两者联系起来的潜在过程。睡眠持续时间的变化与胰岛素样生长因子-I (IGF-I) 水平的变化平行,IGF-I 是一种合成代谢激素,在循环中显示出昼夜节律模式,并依赖于大脑的活动。然而,IGF-I 在这个普遍的稳态过程中的具体作用(如果有的话)仍然知之甚少。我们现在报告说,食欲素神经元的活动是由 IGF-I 调节的,该神经元是下丘脑外侧参与昼夜节律睡眠/觉醒周期和唤醒的离散细胞群。此外,食欲素神经元中 IGF-I 受体活性减弱的小鼠下丘脑中的食欲素水平较低,显示改变的脑电图模式,主要是慢波活动,并减少了入睡潜伏期。总的来说,这些结果将这种多效性生长因子在大脑中的作用扩展到通过调节食欲素神经元来塑造睡眠结构。我们推测与不同条件相关的睡眠质量差可能与大脑 IGF-I 输入到食欲素神经元的紊乱有关。
更新日期:2020-10-08
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