Sleep/wake fragmentation disrupts metabolism in a mouse model of narcolepsy
Sleep/wake fragmentation disrupts metabolism in a mouse model of narcolepsy
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DOI：
10.1113/jphysiol.2007.129510
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发表时间：
2007-06
期刊：
影响因子：
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通讯作者：
Shengwen Zhang;J. Zeitzer;T. Sakurai;S. Nishino;E. Mignot
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文献类型：
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作者：
Shengwen Zhang;J. Zeitzer;T. Sakurai;S. Nishino;E. Mignot
最近的人口研究已经确定了睡眠时间和体重调节之间的重要相互关系。下丘脑/食欲素神经肽系统能够影响其中的每一个。下丘脑泌素系统的紊乱，如发作性睡病，会导致睡眠中断，并经常与身体质量指数增加有关。我们通过测量运动、进食、饮酒、体温、睡眠/觉醒和能量代谢在发作性睡病小鼠模型(消融下丘脑分泌素表达神经元)中的作用，研究了下丘脑分泌素系统、新陈代谢和睡眠之间的潜在相互关系。我们发现发作性睡病小鼠的活动、进食、饮酒和能量消耗显著减少。这些小鼠还表现出严重的睡眠/醒来碎片。觉醒后，转基因小鼠和对照小鼠的活动和食物/水摄入量随时间的增加速度相似。缺乏长觉醒部分或全部解释了在这些转基因小鼠中观察到的总体运动、进食和饮酒的差异。像其他参数一样，能量消耗也随着睡眠/清醒状态的不同而上升和下降。然而，与其他参数不同的是，对照组小鼠醒来后能量消耗增加的速度比发作性睡病小鼠更快。我们的结论是，睡眠/觉醒的严重碎片化是发作性睡病小鼠在不受干扰的情况下运动、摄食、饮水和能量消耗减少的主要原因。我们还确定了下丘脑泌素系统在能量消耗中的内在作用，这种作用可能不依赖于睡眠/觉醒调节、运动或食物摄入量。这项研究表明，在睡眠/清醒模式改变的小鼠模型中，需要对多种表型进行协调研究。
Recent population studies have identified important interrelationships between sleep duration and body weight regulation. The hypothalamic hypocretin/orexin neuropeptide system is able to influence each of these. Disruption of the hypocretin system, such as occurs in narcolepsy, leads to a disruption of sleep and is often associated with increased body mass index. We examined the potential interrelationship between the hypocretin system, metabolism and sleep by measuring locomotion, feeding, drinking, body temperature, sleep/wake and energy metabolism in a mouse model of narcolepsy (ataxin‐ablation of hypocretin‐expressing neurons). We found that locomotion, feeding, drinking and energy expenditure were significantly reduced in the narcoleptic mice. These mice also exhibited severe sleep/wake fragmentation. Upon awakening, transgenic and control mice displayed a similar rate of increase in locomotion and food/water intake with time. A lack of long wake episodes partially or entirely explains observed differences in overall locomotion, feeding and drinking in these transgenic mice. Like other parameters, energy expenditure also rose and fell depending on the sleep/wake status. Unlike other parameters, however, energy expenditure in control mice increased upon awakening at a greater rate than in the narcoleptic mice. We conclude that the profound sleep/wake fragmentation is a leading cause of the reduced locomotion, feeding, drinking and energy expenditure in the narcoleptic mice under unperturbed conditions. We also identify an intrinsic role of the hypocretin system in energy expenditure that may not be dependent on sleep/wake regulation, locomotion, or food intake. This investigation illustrates the need for coordinated study of multiple phenotypes in mouse models with altered sleep/wake patterns.