Bastianini Stefano, Alvente Sara, Berteotti Chiara, Lo Martire Viviana, Matteoli Gabriele, Miglioranza Elena, Silvani Alessandro, Zoccoli Giovanna
Laboratory of Physiological Regulation in Sleeping Mice (PRISM), Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
J Sleep Res. 2025 Apr;34(2):e14287. doi: 10.1111/jsr.14287. Epub 2024 Jul 20.
Narcolepsy type-1 (NT1) is a lifelong sleep disease, characterised by impairment of the orexinergic system, with a typical onset during adolescence and young adulthood. Since the wake-sleep cycle physiologically changes with ageing, this study aims to compare sleep patterns between orexin-knockout (KO) and wild type (WT) control mice at different ages. Four groups of age-matched female KO and WT mice (16 weeks of age: 8 KO-YO and 9 WT-YO mice; 87 weeks of age: 13 KO-OLD and 12 WT-OLD mice) were implanted with electrodes for discriminating wakefulness, rapid-eye-movement sleep (REMS), and non-REMS (NREMS). Mice were recorded for 48 h in their home cages and for 7 more hours into a plethysmographic chamber to characterise their sleep-breathing pattern. Regardless of orexin deficiency, OLD mice spent less time awake and had fragmentation of this behavioural state showing more bouts of shorter length than YO mice. OLD mice also had more NREMS bouts and less frequent NREMS apneas than YO mice. Regardless of age, KO mice showed cataplexy-like episodes and shorter REMS latency than WT controls and had a faster breathing rate and an increased minute ventilation during REMS. KO mice also had more wakefulness, NREMS and REMS bouts, and a shorter mean length of wakefulness bouts than WT controls. Our experiment indicated that the lack of orexins as well as ageing importantly modulate the sleep and breathing phenotype in mice. The narcoleptic phenotype caused by orexin deficiency in female mice was substantially preserved with ageing.
1型发作性睡病（NT1）是一种终身性睡眠疾病，其特征为食欲素能系统受损，典型发病期在青春期和成年早期。由于清醒-睡眠周期会随着年龄增长而发生生理性变化，本研究旨在比较不同年龄的食欲素基因敲除（KO）小鼠和野生型（WT）对照小鼠的睡眠模式。将四组年龄匹配的雌性KO小鼠和WT小鼠（16周龄：8只KO-青年小鼠和9只WT-青年小鼠；87周龄：13只KO-老年小鼠和12只WT-老年小鼠）植入电极，以区分清醒、快速眼动睡眠（REMS）和非快速眼动睡眠（NREMS）。将小鼠置于其饲养笼中记录48小时，并在体积描记室中再记录7小时，以确定其睡眠呼吸模式。无论是否缺乏食欲素，老年小鼠清醒时间较少，且这种行为状态存在碎片化，与青年小鼠相比，其清醒发作次数更多且每次发作时间更短。老年小鼠的NREMS发作次数也更多，NREMS呼吸暂停频率比青年小鼠更低。无论年龄如何，KO小鼠都表现出猝倒样发作，REMS潜伏期比WT对照小鼠短，且呼吸频率更快，在REMS期间每分通气量增加。KO小鼠的清醒、NREMS和REMS发作次数也比WT对照小鼠更多，且清醒发作的平均时长比WT对照小鼠更短。我们的实验表明，食欲素缺乏以及衰老都会显著调节小鼠的睡眠和呼吸表型。雌性小鼠因食欲素缺乏导致的发作性睡病表型在衰老过程中基本得以保留。
