Center for Research in Neuroscience of Lyon (CRNL), SLEEP Team, CNRS UMR 5292, INSERM U1028, Centre Hospitalier le Vinatier-Bâtiment 462-Neurocampus Michel Jouvet, Bron Cedex, France.
University Lyon1, Lyon, France.
Sleep. 2022 Jul 11;45(7). doi: 10.1093/sleep/zsac089.
Narcolepsy type 1 (NT1) is a rare neurology disorder caused by the loss of orexin/hypocretin neurons. NT1 is characterized by excessive daytime sleepiness, sleep and wake fragmentation, and cataplexy. These symptoms have been equally described in both women and men, although influences of gender and hormonal cycles have been poorly studied. Unfortunately, most studies with NT1 preclinical mouse models, use only male mice to limit potential variations due to the hormonal cycle. Therefore, whether gender and/or hormonal cycles impact the expression of narcoleptic symptoms remains to be determined. To address this question, we analyzed vigilance states and cataplexy in 20 female and 17 male adult orexin knock-out narcoleptic mice, with half of the females being recorded over multiple days. Mice had access to chocolate to encourage the occurrence of cataplectic episodes. A vaginal smear was performed daily in female mice to establish the state of the estrous cycle (EC) of the previous recorded night. We found that vigilance states were more fragmented in males than females, and that females had less paradoxical sleep (p = 0.0315) but more cataplexy (p = 0.0375). Interestingly, sleep and wake features were unchanged across the female EC, but the total amount of cataplexy was doubled during estrus compared to other stages of the cycle (p = 0.001), due to a large increase in the number of cataplexy episodes (p = 0.0002). Altogether these data highlight sex differences in the expression of narcolepsy symptoms in orexin knock-out mice. Notably, cataplexy occurrence was greatly influenced by estrous cycle. Whether it is due to hormonal changes would need to be further explored.
发作性睡病 1 型（NT1）是一种罕见的神经紊乱疾病，由食欲素/下丘脑分泌素神经元缺失引起。NT1 的特征是白天过度嗜睡、睡眠和觉醒碎片化以及猝倒。这些症状在女性和男性中同样有描述，尽管性别和激素周期的影响尚未得到充分研究。不幸的是，大多数 NT1 临床前小鼠模型的研究仅使用雄性小鼠，以限制因激素周期而导致的潜在变化。因此，性别和/或激素周期是否会影响发作性睡病症状的表达仍有待确定。为了解决这个问题，我们分析了 20 只雌性和 17 只雄性成年食欲素敲除发作性睡病小鼠的警觉状态和猝倒，其中一半雌性小鼠连续多天记录。为了鼓励猝倒发作，给小鼠提供了巧克力。每天对雌性小鼠进行阴道涂片，以确定前一晚的动情周期（EC）状态。我们发现雄性小鼠的警觉状态比雌性小鼠更为碎片化，而且雌性小鼠的异相睡眠较少（p = 0.0315），但猝倒较多（p = 0.0375）。有趣的是，睡眠和觉醒特征在整个雌性 EC 中没有变化，但与周期的其他阶段相比，发情期的总猝倒量增加了一倍（p = 0.001），这是由于猝倒发作次数的大量增加（p = 0.0002）。总的来说，这些数据强调了在食欲素敲除小鼠中，性别对发作性睡病症状表达的差异。值得注意的是，猝倒的发生受到动情周期的极大影响。是否与激素变化有关，还需要进一步探讨。
