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.

项目概要 睡眠对于健康的身心至关重要，从无脊椎动物到人类都有睡眠。 多种功能，包括记忆巩固、清除有害代谢物以及预防 越来越多的证据表明氧化应激和过早死亡之间存在双向关系。 睡眠和神经退行性疾病，如阿尔茨海默病（AD）患者经常受到睡眠困扰。 重要的是，改善睡眠可以改善 AD 病症。 AD 果蝇模型中的记忆缺陷，表明与睡眠相关的干预措施可能是一种有效的方法 治疗 AD 患者的策略。睡眠受多个过程调节，包括感觉过程。 轶事观察表明，轻轻摇晃或弹跳时，婴儿睡得更好，而且有一些 实验研究证实，摇晃可以促进人类和小鼠的睡眠。 这种有趣现象的潜在机制尚不清楚，果蝇的睡眠与人类相似。 睡眠，我们最近发现温和的振动可以促进果蝇的睡眠，这为 揭示机械刺激诱导睡眠的机制我们发现果蝇睡眠时间更长。 在振动期间和随后较短的睡眠期间，表明振动诱导​​的睡眠（VIS）会导致 初步数据表明 VIS 还可以挽救因睡眠不足而导致的记忆缺陷。 并增强对氧化应激的抵抗力，GABA 信号减弱的果蝇在睡眠期间不会睡得更多。 振动，初步数据表明，通过一种称为利尿激素 44 的神经肽发出的信号是 基于这些结果，拟议的研究将调查 VIS 是否具有影响力。 正常睡眠对 AD 果蝇模型的认知和健康益处，并发现分子和神经 我们的工作将为研究睡眠机制提供一个新的平台。 通过重复的机械感觉刺激进行调节，可能表明与睡眠相关的非侵入性 对 AD 患者进行干预。