Hypocretin underlies the evolution of sleep loss in the Mexican cavefish
Hypocretin underlies the evolution of sleep loss in the Mexican cavefish
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DOI：
10.1101/122903
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发表时间：
2017-03
期刊：
影响因子：
7.7
通讯作者：
James B. Jaggard;B. A. Stahl;Evan Lloyd;D. Prober;Erik R. Duboue;A. Keene
中科院分区：
文献类型：
--
作者：
James B. Jaggard;B. A. Stahl;Evan Lloyd;D. Prober;Erik R. Duboue;A. Keene
不同物种的睡眠持续时间差异很大，但人们对导致这种行为差异的遗传基础或进化因素知之甚少。墨西哥洞穴鱼，Astyanax mexicanus，作为居住在河流中的地表种群存在，以及多个独立衍生的洞穴种群，它们在睡眠缺失方面进化趋同。洞穴鱼下丘脑中HCRT （Hypocretin/Orexin）阳性的神经元数量显著增加，且HCRT在转录物和蛋白水平上均上调。药理或基因抑制HCRT信号会增加洞穴鱼的睡眠时间，而不影响表层鱼的睡眠，这表明HCRT信号增强是洞穴鱼睡眠不足的基础。侧线消融或饥饿，选择性促进洞穴鱼睡眠的操作，抑制洞穴鱼的hcrt表达，而对表层鱼几乎没有影响。这些发现提供了遗传和神经元变化导致睡眠缺失进化的第一个证据，并支持HCRT在睡眠调节中的保守作用。
The duration of sleep varies dramatically between species, yet little is known about genetic bases or evolutionary factors driving this variation in behavior. The Mexican cavefish, Astyanax mexicanus, exists as surface populations that inhabit rivers, and multiple independently derived cave populations with convergent evolution on sleep loss. The number of Hypocretin/Orexin (HCRT)-positive hypothalamic neurons is increased significantly in cavefish, and HCRT is upregulated at both the transcript and protein levels. Pharmacological or genetic inhibition of HCRT signaling increases sleep duration in cavefish without affecting sleep in surface fish, suggesting enhanced HCRT signaling underlies sleep loss in cavefish. Ablation of the lateral line or starvation, manipulations that selectively promote sleep in cavefish, inhibit hcrt expression in cavefish while having little effect in surface fish. These findings provide the first evidence of genetic and neuronal changes that contribute to the evolution of sleep loss, and support a conserved role for HCRT in sleep regulation.