Developmental divergence of sleep-wake patterns in orexin knockout and wild-type mice
Developmental divergence of sleep-wake patterns in orexin knockout and wild-type mice
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DOI：
10.1111/j.1460-9568.2006.05292.x
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Shaw, Cynthia
中科院分区：
文献类型：
--
作者：
Blumberg, Mark S.;Coleman, Cassandra M.;Shaw, Cynthia
发作性睡病是一种以白天和夜间间歇性睡眠和清醒以及猝倒为特征的疾病，在人类和非人类动物中，与食欲素能系统的功能完整性有关。成年食欲素基因敲除小鼠和具有食欲素受体突变的狗表现出的症状与患有发作性睡病的人类相似。与发作性睡病一样，人类和大鼠的婴儿睡眠-觉醒周期是高度分散的，睡眠和觉醒的巩固发作是逐渐发展的。基于嗜睡症患者和婴儿的这些共同特征，我们假设食欲素基因敲除小鼠的睡眠-觉醒碎片化的发展将表现为基因敲除小鼠和野生型小鼠之间的发育差异，其中敲除小鼠落后于野生型小鼠。我们通过记录婴儿食欲素敲除小鼠和野生型小鼠在出生后前三周的睡眠-觉醒模式来检验这一假设。敲除型和野生型都表现出年龄依赖性、因此不依赖于食欲素的睡眠-觉醒模式的量和质的变化。然而，在 3 周龄时，野生型的睡眠和觉醒发作进一步巩固，敲除小鼠落后于野生型，并且表现出明显更多的发作碎片化。这些发现表明，成人发作性睡病特征的行为状态的碎片化可能反映了婴儿期特征的更加碎片化的睡眠-觉醒模式的回归。
Narcolepsy, a disorder characterized by fragmented bouts of sleep and wakefulness during the day and night as well as cataplexy, has been linked in humans and nonhuman animals to the functional integrity of the orexinergic system. Adult orexin knockout mice and dogs with a mutation of the orexin receptor exhibit symptoms that mirror those seen in narcoleptic humans. As with narcolepsy, infant sleep-wake cycles in humans and rats are highly fragmented, with consolidated bouts of sleep and wakefulness developing gradually. Based on these common features of narcoleptics and infants, we hypothesized that the development of sleep-wake fragmentation in orexin knockout mice would be expressed as a developmental divergence between knockouts and wild-types, with the knockouts lagging behind the wild-types. We tested this hypothesis by recording the sleep-wake patterns of infant orexin knockout and wild-type mice across the first three postnatal weeks. Both knockouts and wild-types exhibited age-dependent, and therefore orexin-independent, quantitative and qualitative changes in sleep-wake patterning. At 3 weeks of age, however, by which time the sleep and wake bouts of the wild-types had consolidated further, the knockouts lagged behind the wild-types and exhibited significantly more bout fragmentation. These findings suggest the possibility that the fragmentation of behavioural states that characterizes narcolepsy in adults reflects reversion back toward the more fragmented sleep-wake patterns that characterize infancy.