Progressive Loss of the Orexin Neurons Reveals Dual Effects on Wakefulness
Progressive Loss of the Orexin Neurons Reveals Dual Effects on Wakefulness
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DOI：
10.5665/sleep.5446
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发表时间：
2016-02-01
期刊：
影响因子：
5.6
通讯作者：
Behn, Cecilia Diniz
中科院分区：
文献类型：
--
作者：
Branch, Abigail F.;Navidi, William;Behn, Cecilia Diniz
研究目的：嗜睡症是由食欲素（也称为下丘脑泌素）神经元的丢失引起的。除了食欲肽，这些神经元释放额外的神经递质，这可能会对睡眠/觉醒行为产生复杂的影响。目前，还不清楚食欲素神经元是否促进觉醒的启动和维持，以及食欲素神经元是否影响睡眠的启动或维持。为了确定食欲素神经元对睡眠/觉醒行为动力学的影响，我们分析了急性食欲素神经元缺失的新型小鼠模型中的睡眠/觉醒结构。方法：我们使用生存分析和其他统计方法分析食欲素-tTA; TetO白喉毒素A小鼠在食欲素神经元变性的不同阶段的睡眠/觉醒结构。结果：食欲素神经元的逐渐丧失大大降低了长时间清醒发作的存活率，但也提高了短暂清醒发作的存活率。此外，与食欲素神经元的损失，小鼠更有可能在前30秒的非快速眼动睡眠，然后不太可能返回到睡眠中的前60秒wakefuls.Conclusions：这些研究结果有助于解释嗜睡症的特点是嗜睡和零碎的睡眠。食欲素神经元损失损害长时间清醒发作的存活，导致觉醒的维持不良，但这种神经元损失也通过增加在睡眠开始时醒来的风险并随后降低快速恢复睡眠的可能性而使睡眠片段化。
Study Objectives: Narcolepsy is caused by loss of the orexin (also known as hypocretin) neurons. In addition to the orexin peptides, these neurons release additional neurotransmitters, which may produce complex effects on sleep/wake behavior. Currently, it remains unknown whether the orexin neurons promote the initiation as well as the maintenance of wakefulness, and whether the orexin neurons influence initiation or maintenance of sleep. To determine the effects of the orexin neurons on the dynamics of sleep/wake behavior, we analyzed sleep/wake architecture in a novel mouse model of acute orexin neuron loss.Methods: We used survival analysis and other statistical methods to analyze sleep/wake architecture in orexin-tTA; TetO diphtheria toxin A mice at different stages of orexin neuron degeneration.Results: Progressive loss of the orexin neurons dramatically reduced survival of long wake bouts, but it also improved survival of brief wake bouts. In addition, with loss of the orexin neurons, mice were more likely to wake during the first 30 sec of nonrapid eye movement sleep and then less likely to return to sleep during the first 60 sec of wakefulness.Conclusions: These findings help explain the sleepiness and fragmented sleep that are characteristic of narcolepsy. Orexin neuron loss impairs survival of long wake bouts resulting in poor maintenance of wakefulness, but this neuronal loss also fragments sleep by increasing the risk of awakening at the beginning of sleep and then reducing the likelihood of quickly returning to sleep.