Neurobiology of Sleep and Circadian Rhythms最新文献

Sleep disruption with aging in senescence-accelerated mice-prone 8 (SAMP8) mice and analysis of factors associated with age-related sleep fragmentation using RNA sequencing of the hypothalamus 衰老加速小鼠（SAMP8）的睡眠中断与衰老，以及使用下丘脑RNA测序分析与年龄相关的睡眠碎片相关的因素

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-12-31 DOI: 10.1016/j.nbscr.2025.100142

Kazuyuki Okamura , Rie Yanagisawa , Miyuki Sato , Takehiro Suzuki , Nobuyoshi Nakajima , Tin-Tin Win-shwe , Eiko Koike

Aging is a risk factor for various disorders, and age-dependent changes in sleep parameters are involved in the pathogenesis of many diseases. Senescence-accelerated mice-prone 8 (SAMP8) have a short lifespan and show a disrupted circadian rhythm. However, little is known about how sleep parameters change with age in SAMP8. In this study, we evaluated changes in sleep parameters with aging in SAMP8 compared with those in senescence-accelerated mouse resistant 1 (SAMR1) as the control. Sleep quantity and fragmentation of sleep were evaluated at 4, 36, and 56 weeks of age using a PiezoSleep® system. The average duration of sleep episodes, reflected as the sleep fragmentation, decreased in an age-dependent manner in both SAMR1 and SAMP8, especially under light phase conditions. Interestingly, while the difference between SAMR1 and SAMP8 was not evident at 4 weeks of age, it was significantly reduced in SAMP8 at 36 and 56 weeks of age. These results suggest that the reduction of average sleep episode duration associated with the aging process was accelerated in SAMP8. To explore the mechanisms underlying the accelerated sleep fragmentation in SAMP8, we performed RNA sequencing on hypothalamic specimens obtained from SAMR1 and SAMP8 at 49 weeks of age, which revealed upregulation of type I interferon (IFN)-responsive genes in the SAMP8 hypothalamus. Furthermore, serum IFN-α levels at 49 weeks of age were higher in SAMP8 compared with those in SAMR1, suggesting that elevated IFN-α production in SAMP8 could be associated with the sleep fragmentation.

衰老是多种疾病的危险因素，睡眠参数的年龄依赖性变化与许多疾病的发病机制有关。衰老加速小鼠易感8 （SAMP8）寿命短，昼夜节律紊乱。然而，人们对SAMP8中睡眠参数如何随年龄变化知之甚少。在这项研究中，我们评估了SAMP8中睡眠参数随衰老的变化，并与衰老加速小鼠抵抗1 （SAMR1）中睡眠参数的变化进行了比较。在4、36和56周龄时，使用PiezoSleep®系统评估睡眠量和睡眠片段。在SAMR1和SAMP8中，睡眠片段的平均持续时间以年龄依赖的方式减少，尤其是在光相条件下。有趣的是，虽然SAMR1和SAMP8在4周龄时差异不明显，但SAMP8在36周龄和56周龄时显著降低。这些结果表明，与衰老过程相关的平均睡眠持续时间的减少在SAMP8中加速。为了探索SAMP8加速睡眠碎片化的机制，我们对49周龄的SAMR1和SAMP8下丘脑标本进行了RNA测序，结果显示SAMP8下丘脑中I型干扰素（IFN）应答基因上调。此外，与SAMR1相比，49周龄时SAMP8的血清IFN-α水平更高，表明SAMP8中IFN-α产生的升高可能与睡眠片段化有关。

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引用次数: 0

The PER2:BRCA1:POU2F1(OCT-1) ternary complex represents a multi-component scaffold model for circadian gene regulation PER2:BRCA1:POU2F1（OCT-1）三元复合物代表了昼夜节律基因调控的多组分支架模型

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-11-30 DOI: 10.1016/j.nbscr.2025.100141

Elizaveta Kadukhina , Siqi Jia , Linda M. Villa , Xiao Yi , Daniel G.S. Capelluto , Jonathan S. Briganti , Anne M. Brown , Carla V. Finkielstein

The circadian clock component PER2 coordinates daily oscillations in gene expression across multiple tissues, yet its role in assembling multi-protein regulatory complexes remains incompletely understood. Here, we report that PER2 nucleates a ternary complex with the tumor suppressor BRCA1 and the transcription factor POU2F1(OCT-1) to impose circadian control on target gene promoters. Using bacterial two-hybrid screening, we identified BRCA1 as a novel PER2-interacting protein. Biochemical mapping revealed that PER2 engages BRCA1 through multiple discrete binding interfaces: PER2 spanning residues 356–574 and 683–872 interact with both the N-terminal (1–400) and C-terminal BRCT (1670–1863) domains of BRCA1. Structural modeling predicted 361 residue contacts between PER2 and BRCA1, substantially more than the 74 contacts predicted for PER2:POU2F1(OCT-1), indicating differential affinities that enable ordered complex assembly. Sequential pull-down assays demonstrated that PER2, BRCA1, and POU domain form a stable ternary complex in vitro, with POU2F1(OCT-1) serving as the DNA-binding platform. Electrophoretic mobility shift assays revealed that pre-assembly of PER2 with POU domain inhibits DNA binding, while BRCA1 is essential for stabilizing PER2 recruitment to DNA-bound POU2F1(OCT-1). Using ESR1 as a functional readout, we demonstrated that this ternary complex directly regulates promoter activity. Circadian transcriptome analysis revealed that Esr1 exhibits robust clock-dependent oscillations that are abolished in Per1/2 double-knockout mice, while Pou2f1 and Brca1 maintain constitutive expression. These findings establish PER2 as a circadian scaffold that assembles multivalent protein complexes to temporally gate transcription, providing mechanistic insight into how circadian disruption can influence target gene expression.

昼夜节律钟组件PER2协调多个组织中基因表达的日常振荡，但其在组装多蛋白调控复合物中的作用仍不完全清楚。在这里，我们报道PER2与肿瘤抑制因子BRCA1和转录因子POU2F1（OCT-1）形成一个三元复合物，对靶基因启动子施加昼夜节律控制。通过细菌双杂交筛选，我们发现BRCA1是一种新的per2相互作用蛋白。生化图谱显示，PER2通过多个离散的结合界面与BRCA1结合：PER2跨越356-574和683-872残基与BRCA1的n端（1-400）和c端BRCT（1670-1863）结构域相互作用。结构建模预测了PER2和BRCA1之间的361个残基接触，大大超过了PER2:POU2F1（OCT-1）预测的74个接触，表明不同的亲和力能够实现有序的复杂组装。序列下拉分析表明，PER2、BRCA1和POU结构域在体外形成稳定的三元配合物，其中POU2F1（OCT-1）作为dna结合平台。电泳迁移率转移分析显示，PER2与POU结构域的预组装抑制DNA结合，而BRCA1对于稳定PER2募集到DNA结合的POU2F1（OCT-1）至关重要。使用ESR1作为功能读出，我们证明了这种三元复合物直接调节启动子活性。昼夜转录组分析显示，在Per1/2双敲除小鼠中，Esr1表现出强大的时钟依赖性振荡，而Pou2f1和Brca1保持组成性表达。这些发现证实了PER2是一个昼夜节律支架，可以组装多价蛋白复合物来暂时控制转录，为昼夜节律中断如何影响靶基因表达提供了机制见解。

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引用次数: 0

Sleep stage classification from ECG using machine learning: Evaluating the impact of signal duration 利用机器学习对ECG进行睡眠阶段分类：评估信号持续时间的影响

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-11-24 DOI: 10.1016/j.nbscr.2025.100140

Mohammadreza Iravani, Sadaf Moharreri

Sleep stage flagging is critical for diagnosing conditions like insomnia, sleep apnea, and narcolepsy. Traditional methods rely on time-intensive manual scoring by experts, limiting scalability and accessibility, especially in resource-limited settings. Automating sleep stage classification through signal processing and machine learning could improve diagnostic efficiency and reduce healthcare burdens. While prior studies have utilized multiple signals such as electroencephalogram (EEG), electromyogram (EMG), and electrocardiogram (ECG), this study focuses solely on ECG to provide a simpler, more accessible solution. By simplifying signal input, the approach enhances feasibility in resource-constrained environments. Features based on heart rate variability (HRV) and Poincaré plot descriptors were extracted and used to train machine learning models for five-stage sleep classification. The approach was evaluated using two publicly available datasets, the Haaglanden Medisch Centrum Sleep Staging Database and the MIT-BIH Polysomnographic Database, which were chosen for their varied recording environments and subject diversity. Neural Networks, K-Nearest Neighbors (KNN), XGBoost, and Random Forest were employed to assess performance. The highest classification accuracy of 67 % was achieved with long-duration ECG recordings, outperforming models trained on shorter segments by 12 %. These findings emphasize the impact of signal duration on classification performance and suggest opportunities to refine sleep stage prediction. The study demonstrates the feasibility of ECG-only systems for portable, low-cost, and scalable sleep monitoring. The insights gained may facilitate the development of more accessible and efficient sleep disorder detection, particularly in low-resource settings.

睡眠阶段标记对于诊断失眠、睡眠呼吸暂停和嗜睡症等疾病至关重要。传统方法依赖于专家耗时的人工评分，限制了可扩展性和可访问性，特别是在资源有限的环境中。通过信号处理和机器学习自动化睡眠阶段分类可以提高诊断效率，减轻医疗负担。虽然之前的研究利用了多种信号，如脑电图（EEG）、肌电图（EMG）和心电图（ECG），但本研究仅关注ECG，以提供更简单、更容易获得的解决方案。通过简化信号输入，提高了该方法在资源受限环境下的可行性。提取基于心率变异性（HRV）和poincar情节描述符的特征，并用于训练机器学习模型进行五阶段睡眠分类。该方法使用两个公开可用的数据集进行评估，Haaglanden医学中心睡眠分期数据库和MIT-BIH多导睡眠图数据库，选择这些数据集是因为它们具有不同的记录环境和受试者多样性。使用神经网络、k近邻（KNN）、XGBoost和随机森林来评估性能。长时间ECG记录达到了67%的最高分类准确率，比短段训练的模型高出12%。这些发现强调了信号持续时间对分类性能的影响，并提出了改进睡眠阶段预测的机会。该研究证明了仅ecg系统用于便携式、低成本和可扩展的睡眠监测的可行性。所获得的见解可能有助于开发更容易获得和有效的睡眠障碍检测，特别是在资源匮乏的环境中。

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引用次数: 0

Cortical excitability is affected by light exposure – Distinct effects in adolescents and young adults 光暴露对皮质兴奋性的影响——在青少年和年轻人中有不同的影响

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-11-19 DOI: 10.1016/j.nbscr.2025.100138

Roya Sharifpour , Fermin Balda , Ilenia Paparella , John Read , Zoé Leysens , Sara Letot , Islay Campbell , Elise Beckers , Fabienne Collette , Christophe Phillips , Mikhail Zubkov , Gilles Vandewalle

Light, particularly blue-wavelength light exerts a broad range of non-image forming (NIF) effects including the stimulation of cognition and alertness and the regulation of mood, sleep and circadian rhythms. However, its underlying brain mechanisms are not fully elucidated. Likewise, whether adolescents show a different NIF sensitivity to light compared to adults is not established. Here, we investigated whether cortical excitability, a basic aspect of brain function that depends on sleep-wake regulation, is affected by blue light and whether the effect is similar in young adults and adolescents. We used transcranial magnetic stimulation coupled to high-density electroencephalography (TMS–EEG) in healthy young adults (N = 13, 24.2 ± 3.4 y) and in adolescents (N = 15, 16.9 ± 1.1 y). Our results showed that, in young adults, blue light affected cortical excitability following an apparent inverted-U relationship, while adolescents' cortical excitability was not significantly different under blue light compared to orange light. In addition, although light did not affect performance on a visuomotor vigilance task completed during the TMS-EEG recordings, cortical excitability was positively correlated to task performance in both age groups. This study provides valuable insights into the complex interplay between light, cortical excitability, and behavior. Our findings highlight the role of age in NIF effects of light, suggesting that brain responses to light differ during developmental periods.

光，尤其是蓝色波长的光具有广泛的非图像形成（NIF）效应，包括刺激认知和警觉性以及调节情绪、睡眠和昼夜节律。然而，其潜在的大脑机制尚未完全阐明。同样，与成年人相比，青少年是否表现出不同的NIF对光的敏感性还没有确定。在这里，我们研究了皮质兴奋性（大脑功能的一个基本方面，依赖于睡眠-觉醒调节）是否受到蓝光的影响，以及这种影响在年轻人和青少年中是否相似。我们在健康青年（N = 13, 24.2±3.4 y）和青少年（N = 15, 16.9±1.1 y）中使用经颅磁刺激联合高密度脑电图（TMS-EEG）。我们的研究结果表明，在年轻人中，蓝光对皮层兴奋性的影响遵循明显的倒u关系，而青少年的皮层兴奋性在蓝光和橙光下没有显著差异。此外，尽管在TMS-EEG记录期间，光对完成的视觉运动警戒任务的表现没有影响，但在两个年龄组中，皮质兴奋性与任务表现呈正相关。这项研究为光、皮质兴奋性和行为之间复杂的相互作用提供了有价值的见解。我们的研究结果强调了年龄在光的NIF效应中的作用，表明大脑对光的反应在发育时期有所不同。

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引用次数: 0

Neuroimaging findings in sleep disorders: A review article 睡眠障碍的神经影像学发现：综述文章

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-11-03 DOI: 10.1016/j.nbscr.2025.100137

Ali Kavehee , Fatemeh Kashaninasab , Mir Farhad Ghalehbandi , Mahboobeh Khoozan

Objective

Sleep disorders including insomnia, obstructive sleep apnea (OSA), narcolepsy and REM sleep behavior disorder (RBD), significantly impair cognition, emotional wellbeing and physical health. This review synthesizes Neuroimaging evidence across major sleep disorders. It also documents knowledge gaps in the literature and provides clear next steps towards better diagnostic and therapeutic steps for sleep disorders.

Methods

PRISMA 2020 guidelines were followed for the systematic review of Neuroimaging studies on sleep disorders, with a comprehensive search of PubMed, Scopus and Google Scholar between 1997 and 2024.

Results

A total of 93 Neuroimaging studies published between 1997 and 2024 were systematically reviewed. Insomnia is characterized by reduced gray matter volume in the prefrontal cortex and hippocampus, increased beta activity in EEG, and decreased frontal lobe metabolism, supporting the hyperarousal model. OSA is associated with cortical thinning, hippocampal atrophy, and disrupted Default Mode Network (DMN) connectivity, correlating with cognitive deficits. Narcolepsy exhibits hypothalamic atrophy, reduced orexin signaling, and abnormal thalamocortical connectivity, explaining excessive daytime sleepiness and cataplexy. Parasomnias, particularly REM sleep behavior disorder (RBD), show neurodegenerative changes in the brainstem and basal ganglia, serving as early markers for synucleinopathies like Parkinson's disease.

Conclusion

Multimodal Neuroimaging and electrophysiological findings provide critical insights into the pathophysiology of sleep disorders, highlighting distinct neural patterns that enhance diagnostic precision and guide targeted interventions. Multimodal imaging approaches are essential for advancing precision medicine in sleep disorder management.

目的睡眠障碍包括失眠、阻塞性睡眠呼吸暂停（OSA）、发作性睡病和快速眼动睡眠行为障碍（RBD），严重损害认知、情绪健康和身体健康。这篇综述综合了主要睡眠障碍的神经影像学证据。它还记录了文献中的知识空白，并为更好地诊断和治疗睡眠障碍提供了明确的下一步措施。方法采用sprisma 2020指南，对1997年至2024年间的睡眠障碍神经影像学研究进行系统评价，并综合检索PubMed、Scopus和谷歌Scholar。结果系统回顾了1997 ~ 2024年间发表的93篇神经影像学研究。失眠的特征是前额皮质和海马灰质体积减少，脑电图β活动增加，额叶代谢减少，支持高觉醒模型。OSA与皮质变薄、海马萎缩和默认模式网络（DMN）连接中断有关，与认知缺陷相关。发作性睡症表现为下丘脑萎缩、食欲素信号减少和丘脑皮质连通性异常，这解释了白天过度嗜睡和猝倒。异睡眠症，特别是快速眼动睡眠行为障碍（RBD），表现出脑干和基底神经节的神经退行性改变，是突触核蛋白病（如帕金森病）的早期标志。结论多模态神经成像和电生理研究结果为睡眠障碍的病理生理学提供了重要的见解，突出了不同的神经模式，提高了诊断精度并指导了有针对性的干预措施。多模态成像方法对于推进睡眠障碍管理的精准医学至关重要。

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引用次数: 0

Chronotype in alpha-tACS: Preliminary evidence hints at sleep quality modulation of aftereffects in evening types in the morning α - tacs的睡眠类型：初步证据表明，睡眠质量调节的后效在晚上类型的早晨

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-11-01 DOI: 10.1016/j.nbscr.2025.100136

Peppi Schulz , Heiko I. Stecher , Christoph S. Herrmann

Transcranial alternating current stimulation (tACS) is a promising tool for research on oscillatory brain activity, yet both behavioral and electrophysiological outcome measures show high variability across studies. One source for this variability might be chronotype and an incidental mismatch between chronotype and the time of the measurement.

14 evening type and 14 morning type participants performed a sustained attention task — once at their chronotypically optimal and once at a non-optimal time of day. TACS was applied for 20 min at the individual alpha frequency over two electrodes located at Cz and Oz. EEG was recorded for 10 min prior to and after stimulation. Sleep timing and quality were assessed with a sleep questionnaire. While planned analyses failed to find effects of stimulation and session timing on alpha power, exploratory analyses revealed that below average sleep quality in evening types in the morning was associated with no changes or unexpected decreases in alpha power after stimulation. Effects of sleep quality were present in the morning for evening types, but neither in the evening session nor in morning types. It is suggested that this effect of sleep quality reflects increased sleepiness, which could impede expected aftereffects of tACS. It is likely that effects of sleepiness might be especially relevant when people are stimulated at a chronotypically non-optimal time. Due to the exploratory nature of these sleep effects and their presence in only a small subgroup leading to low power and confidence, future systematic sham-controlled studies are needed to clarify the relationship between sleep, time of day and chronotype in

α

-tACS proposed here.

经颅交流电刺激（tACS）是研究振荡脑活动的一种很有前途的工具，但行为和电生理结果测量在研究中显示出很高的可变性。这种差异的一个来源可能是时间类型，以及时间类型和测量时间之间偶然的不匹配。14名晚睡型和14名早睡型的参与者执行了一项持续注意力任务——一次是在他们的最佳时间，一次是在一天中的非最佳时间。在位于Cz和Oz的两个电极上以单个α频率施加TACS 20分钟。记录刺激前后10分钟的脑电图。通过睡眠问卷对睡眠时间和质量进行评估。虽然计划分析未能发现刺激和会话时间对α功率的影响，但探索性分析显示，晚上类型的早晨低于平均睡眠质量与刺激后α功率没有变化或意外下降有关。对于晚睡型的人来说，睡眠质量在早上出现了影响，但在晚睡型和早起型的人身上都没有。我们认为，这种睡眠质量的影响反映了嗜睡的增加，这可能会阻碍tACS预期的后遗症。当人们在一个典型的非最佳时间受到刺激时，困倦的影响可能会特别相关。由于这些睡眠效应的探索性，以及它们只存在于一个小的亚组，导致低功率和信心，未来需要系统的假对照研究来阐明睡眠、一天中的时间和α-tACS中生物钟类型之间的关系。

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引用次数: 0

Identification of photoperiod as a regulator of dopamine-mediated behavior in female mice 鉴定光周期在雌性小鼠多巴胺介导行为中的调节作用

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-08-17 DOI: 10.1016/j.nbscr.2025.100135

Beimnet B. Kassaye , Alexis N. Jameson , Katherine Moore , Douglas G. McMahon , Brad A. Grueter

Photoperiod is the primary environmental cue that regulates changes in behavior across seasons. Previously, we have shown that photoperiod has sex-specific effects on synaptic dopamine dynamics in the nucleus accumbens (NAc). Further, evidence suggests that the dopamine transporter (DAT) is a potential locus of action for the sex-specific effects of photoperiod on NAc dopamine. The NAc is a critical node within the reward circuit that brings motivation to action, and changes to NAc dopamine dynamics at the synapse can result in robust changes in behaviors. Cocaine is a psychostimulant that targets monoamine transporters, including DAT, and generates robust behavioral effects. Thus, using cocaine-mediated behavior, we can determine whether photoperiod impacts DAT function and dopamine physiology. Here, using male and female mice we examined the effect of seasonally relevant photoperiods on DAT function in the NAc and dopamine-dependent behavior. We found that females raised in Short, winter-like photoperiod have blunted cocaine-induced hyperlocomotion. Conversely, females raised in Long, summer-like photoperiod exhibit greater DA release and cocaine-mediated DAT inhibition while we observe decreased sensitivity to cocaine-associated learning. The combined work presented here provides evidence that photoperiod has differential, female-specific effects on NAc DAT function and DAT-mediated behaviors.

光周期是调节不同季节行为变化的主要环境线索。之前，我们已经证明光周期对伏隔核（NAc）突触多巴胺动力学具有性别特异性影响。此外，有证据表明，多巴胺转运蛋白（DAT）是光周期对NAc多巴胺的性别特异性影响的潜在作用位点。NAc是奖励回路中的一个关键节点，它会给行为带来动机，突触中NAc多巴胺动态的变化会导致行为的强烈变化。可卡因是一种针对单胺转运体的精神兴奋剂，包括DAT，并产生强大的行为效应。因此，利用可卡因介导的行为，我们可以确定光周期是否影响DAT功能和多巴胺生理。在这里，我们使用雄性和雌性小鼠，研究了与季节相关的光周期对NAc中DAT功能和多巴胺依赖行为的影响。我们发现，在短的，类似冬季的光周期中长大的雌性会减弱可卡因引起的过度运动。相反，在类似夏季的长光周期中长大的雌性表现出更多的DA释放和可卡因介导的DAT抑制，而我们观察到对可卡因相关学习的敏感性降低。本文提出的综合工作提供了证据，证明光周期对NAc DAT功能和DAT介导的行为具有不同的、女性特异性的影响。

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引用次数: 0

Effects of DNA methylation inhibitors on light-induced circadian clock plasticity DNA甲基化抑制剂对光诱导的生物钟可塑性的影响

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-08-13 DOI: 10.1016/j.nbscr.2025.100134

Suil Kim , Douglas G. McMahon

The suprachiasmatic nucleus (SCN) of the hypothalamus is a principal light-responsive circadian clock that adjusts circadian rhythms in mammalian physiology and behavior to changes in external light signals. Although mechanisms underlying how light acutely resets the timing of circadian rhythms have been characterized, it remains elusive how light signals induce lasting changes in circadian period, known as period after-effects. Here we have found that the period after-effects on circadian behavior of changing photoperiods are blocked by application of the DNA methyltransferase inhibitor RG108 near the SCN. At the level of single light pulses acting as clock-resetting stimulations, RG108 significantly attenuates period after-effects following acute phase shifts in behavioral rhythms in vivo, and blocks period after-effects on clock gene rhythms following phase resetting by the vasoactive intestinal peptide in the isolated ex vivo SCN. In addition, the DNA methyltransferase inhibitor SGI-1027 blocked period after-effects of optogenetic neuronal stimulation on ex vivo SCN rhythms. Acute clock resetting shifts themselves, however, do not appear to require DNA methylation at the SCN and behavioral levels, in contrast to subsequent period plasticity. Our results demonstrate that DNA methylation inhibitors block light-induced period after-effects in response to photoperiods and single light pulses. Together with previous studies showing that DNA methylation in the SCN is essential for period after-effects of non-24hr light cycles (T-cycles), this suggests that DNA methylation in the SCN may be a widespread mechanism of light-induced circadian period plasticity.

下丘脑的视交叉上核（SCN）是一个主要的光反应生物钟，根据外部光信号的变化调节哺乳动物生理和行为的昼夜节律。尽管光如何重置昼夜节律的机制已经被表征，但光信号如何诱导昼夜节律周期的持续变化，即所谓的周期后效，仍然是难以捉摸的。本研究发现，在SCN附近应用DNA甲基转移酶抑制剂RG108可以阻断光周期变化对昼夜行为的周期后效。在单光脉冲作为生物钟重置刺激的水平上，RG108显著减弱了体内行为节律急性相移后的周期后效，并阻断了离体SCN中血管活性肠肽对生物钟基因节律的周期后效。此外，DNA甲基转移酶抑制剂SGI-1027阻断了光遗传神经元刺激对体外SCN节律的周期后效。然而，与随后的可塑性相比，急性时钟重置本身似乎不需要在SCN和行为水平上的DNA甲基化。我们的研究结果表明，DNA甲基化抑制剂在响应光周期和单光脉冲时可以阻断光诱导期的后效。先前的研究表明，SCN中的DNA甲基化对于非24小时光周期（t周期）的周期后效应至关重要，这表明SCN中的DNA甲基化可能是光诱导的昼夜节律周期可塑性的广泛机制。

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引用次数: 0

Sleep regularity and duration are associated with depression severity in a nationally representative United States sample 在具有全国代表性的美国样本中，睡眠规律和持续时间与抑郁症严重程度有关

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-07-17 DOI: 10.1016/j.nbscr.2025.100133

Katherine A. Maki, Li Yang, Nicole Farmer, Shreya Papneja, Gwenyth R. Wallen, Jennifer J. Barb

Background

Sleep hygiene is integral to health, and sleep regularity may be associated with mental health outcomes in addition to duration. Although sleep and depression relationships are well-studied, the relative impact of different sleep factors remains unclear. As patient-specific factors and health behaviors influence sleep and mental health, we investigated associations between sleep and depression severity considering such factors in a United States sample of adults.

Methods

Two cycles (2011–2012, 2013–2014) from the National Health and Nutritional Examination Survey were studied. Objective sleep duration (day and night), and the sleep regularity index (SRI) were calculated from physical activity monitors worn for seven days. Complex survey procedures with four-year weights were used, and backward selection was used to test relevant variables in the fully adjusted regression model.

Results

Among participants (n = 7297), we found associations between sleep-associated variables and SRI, with increased daytime sleep being the strongest correlate of decreased SRI. In the fully adjusted model, lower SRI scores and reduced subjective night sleep remained significantly associated with depression. Sex was an additional independent predictor, with females exhibiting higher depression scores, and a significant sex × SRI interaction revealed that the inverse relationship between SRI and depressive symptoms was stronger in females than in males. Health behaviors, including active tobacco and cannabis use, were also associated with increased depression severity in the adjusted model.

Conclusions

Daytime sleep may serve as an SRI proxy, although additional cohorts should confirm relationships. Higher depression severity was associated with different sleep components, emphasizing the importance of sleep hygiene in mental health. Behaviors like current smoking and cannabis use were also associated with increased depression. Research exploring the temporality and interactions between these factors may assist in non-pharmacologic depression treatment.

睡眠卫生是健康不可或缺的一部分，除了持续时间外，睡眠规律可能与心理健康结果有关。尽管睡眠和抑郁的关系已经得到了充分的研究，但不同睡眠因素的相对影响仍不清楚。由于患者特有的因素和健康行为影响睡眠和心理健康，我们在美国成年人样本中考虑了这些因素，调查了睡眠和抑郁严重程度之间的关系。方法对2011-2012年、2013-2014年两个周期的全国健康与营养检查调查进行分析。客观睡眠时间（白天和黑夜）和睡眠规律指数（SRI）由佩戴7天的身体活动监测仪计算。采用四年权的复杂调查程序，并采用逆向选择对完全调整回归模型中的相关变量进行检验。在参与者（n = 7297）中，我们发现睡眠相关变量与SRI之间存在关联，白天睡眠增加与SRI降低的相关性最强。在完全调整的模型中，较低的SRI得分和较少的主观夜间睡眠仍然与抑郁症显著相关。性别是另一个独立的预测因子，女性表现出更高的抑郁评分，显著的性别× SRI交互作用表明，女性的SRI与抑郁症状之间的负相关强于男性。在调整后的模型中，健康行为，包括积极使用烟草和大麻，也与抑郁症严重程度的增加有关。结论：白天睡眠可以作为SRI的替代指标，但需要更多的队列来证实两者之间的关系。较高的抑郁严重程度与不同的睡眠成分有关，强调了睡眠卫生对心理健康的重要性。目前吸烟和使用大麻等行为也与抑郁症的增加有关。探索这些因素之间的时间性和相互作用的研究可能有助于非药物治疗抑郁症。

{"title":"Sleep regularity and duration are associated with depression severity in a nationally representative United States sample","authors":"Katherine A. Maki, Li Yang, Nicole Farmer, Shreya Papneja, Gwenyth R. Wallen, Jennifer J. Barb","doi":"10.1016/j.nbscr.2025.100133","DOIUrl":"10.1016/j.nbscr.2025.100133","url":null,"abstract":"<div><h3>Background</h3><div>Sleep hygiene is integral to health, and sleep regularity may be associated with mental health outcomes in addition to duration. Although sleep and depression relationships are well-studied, the relative impact of different sleep factors remains unclear. As patient-specific factors and health behaviors influence sleep and mental health, we investigated associations between sleep and depression severity considering such factors in a United States sample of adults.</div></div><div><h3>Methods</h3><div>Two cycles (2011–2012, 2013–2014) from the National Health and Nutritional Examination Survey were studied. Objective sleep duration (day and night), and the sleep regularity index (SRI) were calculated from physical activity monitors worn for seven days. Complex survey procedures with four-year weights were used, and backward selection was used to test relevant variables in the fully adjusted regression model.</div></div><div><h3>Results</h3><div>Among participants (n = 7297), we found associations between sleep-associated variables and SRI, with increased daytime sleep being the strongest correlate of decreased SRI. In the fully adjusted model, lower SRI scores and reduced subjective night sleep remained significantly associated with depression. Sex was an additional independent predictor, with females exhibiting higher depression scores, and a significant sex × SRI interaction revealed that the inverse relationship between SRI and depressive symptoms was stronger in females than in males. Health behaviors, including active tobacco and cannabis use, were also associated with increased depression severity in the adjusted model.</div></div><div><h3>Conclusions</h3><div>Daytime sleep may serve as an SRI proxy, although additional cohorts should confirm relationships. Higher depression severity was associated with different sleep components, emphasizing the importance of sleep hygiene in mental health. Behaviors like current smoking and cannabis use were also associated with increased depression. Research exploring the temporality and interactions between these factors may assist in non-pharmacologic depression treatment.</div></div>","PeriodicalId":37827,"journal":{"name":"Neurobiology of Sleep and Circadian Rhythms","volume":"19 ","pages":"Article 100133"},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of MeCP2 leads to sleep deficits that are time-of-day dependent and worsen with sleep deprivation MeCP2的缺失会导致睡眠不足，这种睡眠不足与时间有关，并随着睡眠剥夺而恶化

Q2 Medicine

Neurobiology of Sleep and Circadian Rhythms

Pub Date : 2025-06-11 DOI: 10.1016/j.nbscr.2025.100132

Abrar Al Maghribi , Caitlin Ottaway , Michael Rempe , Elizabeth Medina , Kaitlyn Ford , Kristan Singletary , Lucia Peixoto

Rett syndrome (RTT) is a severe, progressive neurodevelopmental disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2). Sleep problems are frequently reported in Rett Syndrome, but the exact nature remains relatively unexplored. Currently there is limited understanding of MECP2's role in sleep architecture and regulation. In this study, we employed longitudinal electroencephalographic (EEG) and electromyographic (EMG) recordings to investigate sleep architecture during baseline conditions as well as the homeostatic response to sleep deprivation (SD) in Mecp2^-/y male mice. At baseline, Mecp2^-/y mice have more non-rapid-eye-movement (NREM) sleep and less rapid-eye-movement (REM) sleep than their wildtype littermates during the light period. However, Mecp2^-/y mice display altered sleep timing during the dark period, spending more time in both NREM and REM during the first half and less time during the second half. Mecp2^-/y mice also have lower EEG spectral power during wake and NREM at higher frequencies and higher power at lower frequencies during REM in compared to wildtype mice. In response to SD, Mecp2^-/y mice can accumulate and discharge sleep pressure normally and show a sleep rebound. However, baseline differences in sleep architecture are heightened after SD. Overall, our findings show that RTT mice exhibit distinct sleep patterns compared to wildtype mice, with time-of-day-dependent variations in NREM and REM sleep, as well as altered EEG spectral properties, that become more pronounced following SD. Future research should explore the molecular mechanisms through which MECP2 regulates sleep architecture to develop targeted therapeutics for sleep disturbances in RTT patients.

Rett综合征（RTT）是一种严重的进行性神经发育障碍，由编码甲基cpg结合蛋白2 （MECP2）的x连锁基因突变引起。睡眠问题经常在Rett综合征中被报道，但确切的性质仍然相对未知。目前对MECP2在睡眠结构和调节中的作用了解有限。在这项研究中，我们使用纵向脑电图（EEG）和肌电图（EMG）记录来研究基线条件下Mecp2-/y雄性小鼠的睡眠结构以及睡眠剥夺（SD）的稳态反应。在基线时，Mecp2-/y小鼠在光照期比野生型小鼠有更多的非快速眼动（NREM）睡眠和更少的快速眼动（REM）睡眠。然而，Mecp2-/y小鼠在黑暗期表现出睡眠时间的改变，在前半段的非快速眼动和快速眼动中花费更多的时间，在后半段花费更少的时间。与野生型小鼠相比，Mecp2-/y小鼠在较高频率的清醒和非快速眼动期间的脑电图频谱功率较低，而在较低频率的快速眼动期间的脑电图频谱功率较高。SD作用下，Mecp2-/y小鼠可正常积累和释放睡眠压力，出现睡眠反弹。然而，在SD后，睡眠结构的基线差异会加剧。总的来说，我们的研究结果表明，与野生型小鼠相比，RTT小鼠表现出不同的睡眠模式，NREM和REM睡眠的时间依赖性变化，以及脑电图频谱特性的改变，在SD后变得更加明显。未来的研究应探索MECP2调控睡眠结构的分子机制，以开发针对RTT患者睡眠障碍的靶向治疗方法。

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引用次数: 0