Shank3 influences mammalian sleep development.
Shank3 influences mammalian sleep development.
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DOI：
10.1002/jnr.25119
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发表时间：
2022-12
影响因子：
4.2
通讯作者：
Peixoto, Lucia
中科院分区：
文献类型：
--
作者：
Medina, Elizabeth;Schoch, Hannah;Ford, Kaitlyn;Wintler, Taylor;Singletary, Kristan G.;Peixoto, Lucia
睡眠问题在自闭症谱系障碍（ASD）中很普遍，可以在诊断前观察到，并且与限制和重复行为的增加有关。因此，睡眠异常可能是这种疾病的核心特征，但其发展轨迹仍然未知。动物模型提供了一个独特的机会，了解睡眠个体发育的ASD。之前，我们发现在高置信度ASD基因Shank 3（Shank 3 C）中具有截短的成年小鼠重现了临床睡眠表型。在这项研究中，我们首次使用纵向脑电图（EEG）记录来定义ASD小鼠模型从断奶到成年早期的睡眠变化。我们发现，Shank 3/C雄性小鼠在其整个生命周期中睡眠总体较少，尽管非快速眼动（NREM）睡眠显着减少，但在生命早期快速眼动（REM）睡眠增加，并且对特定发育期间出现的睡眠压力增加有异常反应。我们证明，小鼠在睡眠不足时迅速入睡的能力在24至30天之间正常发展。然而，突变体无法在长时间清醒后减少睡眠潜伏期，并且无论年龄如何，都无法对睡眠不足保持相同的反应。这种现象似乎独立于稳态NREM睡眠慢波动力学。总的来说，我们的研究概括了临床前模型和临床研究，表明睡眠减少与ASD一致相关，并表明入睡问题可能反映了睡眠和唤醒机制的异常发展。孤独症在自闭症谱系障碍（ASD）中很普遍，严重影响生活质量。使用ASD小鼠模型，我们发现睡眠问题从年轻时就存在，并随着时间的推移而恶化，支持异常睡眠作为ASD的核心特征。
Sleep problems are prevalent in autism spectrum disorder (ASD), can be observed before diagnosis, and are associated with increased restricted and repetitive behaviors. Therefore, sleep abnormalities may be a core feature of the disorder, but the developmental trajectory remains unknown. Animal models provide a unique opportunity to understand sleep ontogenesis in ASD. Previously we showed that adult mice with a truncation in the high‐confidence ASD gene Shank3 (Shank3∆C) recapitulate the clinical sleep phenotype. In this study we used longitudinal electro‐encephalographic (EEG) recordings to define, for the first time, changes in sleep from weaning to young adulthood in an ASD mouse model. We show that Shank3∆C male mice sleep less overall throughout their lifespan, have increased rapid eye movement (REM) sleep early in life despite significantly reduced non‐rapid eye movement (NREM) sleep, and have abnormal responses to increased sleep pressure that emerge during a specific developmental period. We demonstrate that the ability to fall asleep quickly in response to sleep loss develops normally between 24 and 30 days in mice. However, mutants are unable to reduce sleep latency after periods of prolonged waking and maintain the same response to sleep loss regardless of age. This phenomenon seems independent of homeostatic NREM sleep slow‐wave dynamics. Overall, our study recapitulates both preclinical models and clinical studies showing that reduced sleep is consistently associated with ASD and suggests that problems falling asleep may reflect abnormal development of sleep and arousal mechanisms. Insomnia is prevalent in Autism Spectrum Disorder (ASD) and heavily influences quality of life. Using a mouse model of ASD we show that sleep problems are present from young ages and worsen with time, supporting abnormal sleep as a core feature of ASD.
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
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影响因子：
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影响因子：
6.7
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