Dual orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexy
Dual orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexy
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DOI：
10.7554/elife.54275
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发表时间：
2020-04-21
期刊：
影响因子：
7.7
通讯作者：
Yamanaka, Akihiro
中科院分区：
文献类型：
--
作者：
Hung, Chi Jung;Ono, Daisuke;Yamanaka, Akihiro
产生食欲素/下丘脑泌素的神经元和产生黑色素浓缩的神经元（MCH）在下丘脑中共同延伸，并投射到整个大脑以调节睡眠/觉醒。食欲素神经元的消融减少觉醒并导致发作性睡病样表型，而MCH神经元的消融增加觉醒。由于目前还不清楚食欲素和MCH神经元如何相互作用来调节睡眠/觉醒，我们产生了食欲素和MCH神经元都可以被消融的转基因小鼠。双消融小鼠表现出觉醒增加，快速眼动（REM）和非REM（NREM）睡眠减少。与食欲素神经元消融小鼠相比，双消融小鼠表现出严重的cataemia，这表明MCH神经元通常抑制cataemia。双消融小鼠还表现出频繁的睡眠发作，并且Delta和Theta范围内的光谱功率升高，这种独特的状态我们称之为“Delta-Theta睡眠”。总之，这些结果表明食欲素和MCH神经元在体内的功能相互作用，这表明这些神经元群体在睡眠/觉醒周期的协同参与。
Orexin/hypocretin-producing and melanin-concentrating hormone-producing (MCH) neurons are co-extensive in the hypothalamus and project throughout the brain to regulate sleep/wakefulness. Ablation of orexin neurons decreases wakefulness and results in a narcolepsy-like phenotype, whereas ablation of MCH neurons increases wakefulness. Since it is unclear how orexin and MCH neurons interact to regulate sleep/wakefulness, we generated transgenic mice in which both orexin and MCH neurons could be ablated. Double-ablated mice exhibited increased wakefulness and decreased both rapid eye movement (REM) and non-REM (NREM) sleep. Double-ablated mice showed severe cataplexy compared with orexin neuron-ablated mice, suggesting that MCH neurons normally suppress cataplexy. Double-ablated mice also showed frequent sleep attacks with elevated spectral power in the delta and theta range, a unique state that we call 'delta-theta sleep'. Together, these results indicate a functional interaction between orexin and MCH neurons in vivo that suggests the synergistic involvement of these neuronal populations in the sleep/wakefulness cycle.