Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants.
Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants.
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DOI：
10.1371/journal.pbio.0050277
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发表时间：
2007-10-16
期刊：
影响因子：
9.8
通讯作者：
Mignot E
中科院分区：
文献类型：
--
作者：
Yokogawa T;Marin W;Faraco J;Pézeron G;Appelbaum L;Zhang J;Rosa F;Mourrain P;Mignot E
睡眠是整个动物界都保留的基本生物过程。为了更好地理解进化过程中的睡眠，需要研究睡眠调节网络如何保存。我们详细描述了成年斑马鱼的睡眠状态，其特征是可逆的不动期、觉醒阈值增加和位置偏好。使用温和的电刺激剥夺休息后会出现睡眠反弹，表明体内平衡调节。与哺乳动物不同，与鸟类类似，光会抑制斑马鱼的睡眠，并且没有证据表明睡眠会反弹。我们还在斑马鱼的促醒神经肽下丘脑分泌素（食欲素）的唯一受体中发现了无效突变。缺乏这种受体的鱼类在黑暗中表现出短暂且不连续的睡眠，这与哺乳动物嗜睡症的过度嗜睡和猝倒形成鲜明对比。与这一观察结果一致，我们发现下丘脑分泌素受体并不与斑马鱼中已知的主要促醒单胺能和胆碱能细胞群共定位。相反，它与大量 GABA 能神经元共定位，包括下丘脑前区的 Adra2a 阳性 GABA 能细胞亚群，这些神经元可以发挥睡眠调节作用。我们的研究验证了斑马鱼在睡眠研究中的用途，并表明脊椎动物睡眠调节网络的分子多样性。睡眠障碍很常见，但人们对其知之甚少。此外，大脑如何以及为何产生睡眠也是人们强烈猜测的对象。在这项研究中，我们证明用于基因研究的硬骨鱼会睡觉，并且与引起发作性睡病有关的下丘脑分泌素分子是保守的。在人类中，发作性睡病是一种与困倦、异常做梦、瘫痪和失眠相关的睡眠障碍。我们培育了一种突变鱼，其中下丘脑分泌素系统被破坏。有趣的是，这种睡眠突变鱼并没有表现出困倦或麻痹，但与非突变鱼相比，其夜间睡眠时间减少了 30%，睡眠时间缩短了 60%。我们还研究了斑马鱼的下丘脑分泌素系统和其他睡眠调节大脑系统之间的关系，发现大脑中表达模式的差异可以解释行为的差异。我们的研究说明了睡眠调节系统是如何在脊椎动物系统发育中进化的。斑马鱼是一种强大的遗传模型，具有透明的优势，可用于研究体内神经元网络，可用于研究睡眠。斑马鱼睡觉时，具有唤醒诱导分子下丘脑分泌素的受体。虽然这种受体的突变会导致哺乳动物出现嗜睡症，但鱼类的睡眠却是支离破碎的，这表明脊椎动物的睡眠控制存在差异。
Sleep is a fundamental biological process conserved across the animal kingdom. The study of how sleep regulatory networks are conserved is needed to better understand sleep across evolution. We present a detailed description of a sleep state in adult zebrafish characterized by reversible periods of immobility, increased arousal threshold, and place preference. Rest deprivation using gentle electrical stimulation is followed by a sleep rebound, indicating homeostatic regulation. In contrast to mammals and similarly to birds, light suppresses sleep in zebrafish, with no evidence for a sleep rebound. We also identify a null mutation in the sole receptor for the wake-promoting neuropeptide hypocretin (orexin) in zebrafish. Fish lacking this receptor demonstrate short and fragmented sleep in the dark, in striking contrast to the excessive sleepiness and cataplexy of narcolepsy in mammals. Consistent with this observation, we find that the hypocretin receptor does not colocalize with known major wake-promoting monoaminergic and cholinergic cell groups in the zebrafish. Instead, it colocalizes with large populations of GABAergic neurons, including a subpopulation of Adra2a-positive GABAergic cells in the anterior hypothalamic area, neurons that could assume a sleep modulatory role. Our study validates the use of zebrafish for the study of sleep and indicates molecular diversity in sleep regulatory networks across vertebrates. Sleep disorders are common and poorly understood. Further, how and why the brain generates sleep is the object of intense speculations. In this study, we demonstrate that a bony fish used for genetic studies sleeps and that a molecule, hypocretin, involved in causing narcolepsy, is conserved. In humans, narcolepsy is a sleep disorder associated with sleepiness, abnormal dreaming, and paralysis and insomnia. We generated a mutant fish in which the hypocretin system was disrupted. Intriguingly, this fish sleep mutant does not display sleepiness or paralysis but has a 30% reduction of its sleep time at night and a 60% decrease in sleep bout length compared with non-mutant fish. We also studied the relationships between the hypocretin system and other sleep regulatory brain systems in zebrafish and found differences in expression patterns in the brain that may explain the differences in behavior. Our study illustrates how a sleep regulatory system may have evolved across vertebrate phylogeny. Zebrafish, a powerful genetic model that has the advantage of transparency to study neuronal networks in vivo, can be used to study sleep. Zebrafish sleep, and have the receptor for the wake-inducing molecule hypocretin. While mutation in this receptor causes narcolepsy in mammals, in fish, sleep is fragmented, demonstrating differences in sleep control in vertebrates.
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影响因子：
3.3
作者：
Brown, R. E.;Winston, S.;McCarley, R. W.
通讯作者：
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DOI：
10.1016/j.bbrc.2006.10.172
发表时间：
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