Sleep induction by repetitive mechanosensory stimulation.

通过重复机械感觉刺激诱导睡眠。

• 批准号: 10608638
• 负责人: Kyunghee Koh
• 金额: $ 42.9万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10608638
• 关键词: Acute; Adult; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Alzheimer' s disease patient; Arctic Regions; Biological Models; Brain; Cessation of life; Cognition; Cognitive; Corticotropin-Releasing Hormone; Data; Defect; Disease Progression; Diuretics; Drosophila genus; Elderly; Exhibits; Fatigue; Frequencies; GABA-B Receptor; Genes; Health; Health Benefit; Homeostasis; Homologous Gene; Hormones; Human; Infant; Intervention; Invertebrates; Mechanical Stimulation; Mediating; Memory; Memory impairment; Mind; Molecular; Motor; Mus; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neurons; Neuropeptides; Neurotoxins; Oxidative Stress; Patients; Pattern; Persons; Play; Prevention; Process; Protocols documentation; Research; Resistance; Role; Sensory; Sensory Process; Short-Term Memory; Signal Pathway; Signal Transduction; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Specificity; Stimulus; Stress; Suggestion; Symptoms; Testing; Work; cognitive benefits; experimental study; familial Alzheimer disease; fly; gamma-Aminobutyric Acid; habituation; improved; insight; knock-down; memory consolidation; neuromechanism; novel; overexpression; premature; receptor; relating to nervous system; sleep regulation; vibration

Project Summary Sleep is essential for a healthy mind and body and is conserved from invertebrates to humans. Sleep serves multiple functions, including memory consolidation, clearance of harmful metabolites, and prevention of oxidative stress and premature death. Accumulating evidence suggests a bidirectional relationship between sleep and neurodegenerative diseases such as Alzheimer’s disease (AD). AD patients often suffer from sleep disruptions, while disrupted sleep accelerates AD pathologies. Importantly, improved sleep can ameliorate memory deficits in a Drosophila model of AD, suggesting that sleep-related interventions could be an effective strategy for treating AD patients. Sleep is regulated by multiple processes, including sensory processes. Anecdotal observations suggest that babies sleep better when gently rocked or bounced, and several experimental studies have confirmed that rocking promotes sleep in humans and mice. However, the underlying mechanisms for this intriguing phenomenon are not well understood. Fly sleep is similar to human sleep, and our recent finding that gentle vibration promotes sleep in flies provides an opportunity for uncovering the mechanisms of sleep induction by mechanical stimulation. We found that flies sleep longer during vibration and sleep shorter afterward, suggesting vibration-induced sleep (VIS) leads to the accumulation of sleep credit. Preliminary data suggest VIS can also rescue memory deficits due to sleep loss and enhance resistance to oxidative stress. Flies with reduced GABA signaling do not sleep more during vibration, and preliminary data suggest that signaling through a neuropeptide called Diuretic Hormone 44 is also involved in VIS. Building on these results, the proposed studies will investigate whether VIS confers cognitive and health benefits of normal sleep in Drosophila models of AD and discover molecular and neural mechanisms underlying VIS. Our work will provide a novel platform to study the mechanisms of sleep regulation by repetitive mechanosensory stimulation and may suggest a non-invasive sleep-related intervention for AD patients.

项目摘要 睡眠对于健康的身心健康是必不可少的，从无脊椎动物到人类都是如此。睡眠是服务的 多种功能，包括巩固记忆，清除有害代谢物，预防 氧化应激和过早死亡。越来越多的证据表明，两者之间存在双向关系 睡眠和神经退行性疾病，如阿尔茨海默病(AD)。AD患者经常失眠 睡眠中断会加速AD的病理。重要的是，改善睡眠可以改善 果蝇阿尔茨海默病模型的记忆缺陷，提示睡眠相关的干预可能是有效的 治疗AD患者的策略。睡眠受到多个过程的调节，包括感觉过程。 坊间观察表明，婴儿在轻轻摇晃或弹跳时睡得更好，还有几个 实验研究证实摇摆对人类和小鼠的睡眠有促进作用。然而， 这一耐人寻味的现象的潜在机制还没有被很好地理解。苍蝇的睡眠与人类相似 睡眠，我们最近发现，温和的振动促进了果蝇的睡眠，这提供了一个机会 揭示机械刺激诱导睡眠的机制。我们发现苍蝇睡得更久 在振动期间和之后睡眠较短的情况下，提示振动诱导睡眠(VIS)会导致 睡眠积分的积累。初步数据表明，VIS还可以修复因睡眠不足而造成的记忆缺陷 增强对氧化应激的抵抗力。GABA信号减弱的果蝇在 振动和初步数据表明，通过一种名为利尿激素44的神经肽发出的信号是 也参与了VIS。在这些结果的基础上，拟议的研究将调查VIS是否 正常睡眠对阿尔茨海默病果蝇模型的认知和健康益处并发现分子和神经 VIS背后的机制。我们的工作将为研究睡眠机制提供一个新的平台 通过重复机械感觉刺激进行调节，并可能提示与睡眠相关的非侵入性 对AD患者的干预。