Ultrashort (msec) Light Exposure as a Countermeasure to Circadian Desynchrony

超短（毫秒）光照作为昼夜节律不同步的对策

• 批准号: 8194843
• 负责人: JAMIE M ZEITZER
• 金额: $ 35.81万
• 依托单位: PALO ALTO VETERANS INSTIT FOR RESEARCH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8194843
• 关键词: Accidents; Adolescent; Affect; Arousal; Brain; Carcinogens; Cardiac; Cell Nucleus; Characteristics; Circadian Rhythms; Cognition; Cognitive; Cues; Delayed Sleep Phase Syndrome; Diabetes Mellitus; Disease; Elements; Endocrine; Ensure; Exposure to; Eyelid structure; Fatigue; Functional disorder; Goals; Growth; Hamsters; Health; Health behavior; Hormones; Hour; Human; Hypothalamic structure; Individual; International Agency for Research on Cancer; Laboratories; Lateral Hypothalamic Area; Lead; Length; Length of Stay; Light; Link; Malignant Neoplasms; Measurement; Measures; Mental Depression; Metabolism; Methods; Moods; Mus; Obesity; Perception; Performance; Phase; Physiologic pulse; Physiological; Physiology; Pilot Projects; Preoptic Areas; Protocols documentation; Rattus; Regimen; Relative (related person); Reporting; Research; Retina; Schedule; Site; Sleep; Sleeplessness; Societies; Stimulus; System; Techniques; Temperature; Testing; Therapeutic; Thinking; Time; Travel; Vertebrates; Workplace; World Health Organization; alertness; arm; awake; cancer risk; circadian pacemaker; cost; design; immune function; improved; light effects; light treatment; millisecond; nerve supply; novel; pressure; relating to nervous system; research study; shift work; social; suprachiasmatic nucleus; young adult

DESCRIPTION (provided by applicant): Circadian desynchrony is a phenomenon that occurs when the internal circadian clock is misaligned with the social schedule that one tries to keep. This arises volitionally in a variety of circumstances, including shift work and jet travel. It leads to significant pathophysiology including deleterious changes in sleep, cognition, metabolism, immune function, and cardiac function, which in turn can lead to, among other things, increases in obesity, cancer risk, and workplace accidents. Circadian desynchrony also occurs naturally in delayed sleep phase disorder (DSPD), a condition in many adolescents and young adults that is compounded by social pressures and causes individuals to shift their sleep time later while their wake time remains fixed. DSPD leads to significant decline in workplace and academic performance and has been linked to a variety of disorders including obesity and depression. Circadian desynchrony is most readily treated by hours of administration of bright light. This, however, is not always possible and our lack of complete understanding of the characteristics of light and how it influences the circadian pacemaker limit our ability to design better countermeasures to circadian desynchrony. It is the purpose of this application to examine the basic physiology of how light influences circadian timing, as well as how light impacts alertness at night and a novel mechanism by which to change circadian timing during sleep. Specifically, we will examine the hypothesis that when subjects are exposed, while awake at night, to ultrashort (millisecond) pulses of light, the light is able to both synchronize the human circadian system and improve alertness, as determined by both subjective and objective measures. In a separate experiment, subjects will be exposed to ultrashort pulses of light at night while they sleep. In that experiment, we intend to examine the hypothesis that this stimulus will not only penetrate the closed eyelid and synchronize the circadian system, but that it will do so without disrupting sleep. In order to examine these hypotheses, young, healthy subjects will be brought into a specially designed human circadian laboratory and exposed to different regimens of light. We introduce in this study a novel protocol that reduces the study length of stay from the standard week to just two days. While greatly reducing subject burden and study costs, we are able to maintain high fidelity measurements of the human circadian system. We will also examine alertness through a variety of techniques including performance tracking and examination of electroencephalographic activity. Results from this experiment will not only fundamentally change the manner in which we think about how light affects the human circadian pacemaker, but it will also lead to direct, testable therapeutics for the treatment of circadian desynchrony. It may also lead to a better understanding of the impact of light on other hypothalamic- influenced functions including mood and endocrine function. PUBLIC HEALTH RELEVANCE: The lack of synchrony between the internal circadian clock and the outside world is increasingly becoming a significant problem in our round-the-clock lives and leads to significant negative health consequences, including an increased cancer risk, workplace accidents, and obesity. In fact, the International Agency for Research on Cancer, the cancer arm of the World Health Organization, classifies shift work as a probable carcinogen. This project intends to examine the brain physiology underlying the synchronization of the internal circadian clock to the external world and will test a novel method of synchronizing this brain clock, one that could lead to a novel therapy for shift workers, jet travelers, and adolescents with delayed sleep phase syndrome.

描述（由申请人提供）：昼夜节律紊乱是一种现象，发生在内部生物钟与社会时间表，一个试图保持不一致。这种情况在各种情况下都会自愿出现，包括轮班工作和喷气式飞机旅行。它导致显著的病理生理学，包括睡眠、认知、代谢、免疫功能和心脏功能的有害变化，这反过来又会导致肥胖、癌症风险和工作场所事故的增加。昼夜节律紊乱也自然发生在睡眠相位延迟障碍（DSPD）中，这是一种在许多青少年和年轻人中发生的疾病，由于社会压力而加剧，导致个人改变他们的睡眠时间，而他们的醒来时间保持固定。DSPD导致工作和学习成绩显著下降，并与包括肥胖和抑郁症在内的各种疾病有关。昼夜节律紊乱最容易通过数小时的强光治疗。然而，这并不总是可能的，我们缺乏对光的特性以及它如何影响昼夜节律起搏器的完整理解，限制了我们设计更好的昼夜节律节律对策的能力。本申请的目的是研究光如何影响昼夜节律的基本生理学，以及光如何影响夜间的警觉性和一种在睡眠期间改变昼夜节律的新机制。具体来说，我们将研究这样一个假设，即当受试者在夜间清醒时暴露于超短（毫秒）光脉冲时，光能够同步人类昼夜节律系统并提高警觉性，这是由主观和客观测量确定的。在另一项实验中，受试者将在晚上睡觉时暴露在超短脉冲光下。在那个实验中，我们打算检验这样一个假设，即这种刺激不仅会穿透闭合的眼睑，使昼夜节律系统同步，而且不会干扰睡眠。为了检验这些假设，年轻健康的受试者将被带入一个专门设计的人类昼夜节律实验室，并暴露在不同的光照下。我们在这项研究中引入了一种新的方案，将研究的住院时间从标准的一周缩短到两天。在大大减少受试者负担和研究成本的同时，我们能够保持对人类昼夜节律系统的高保真测量。我们还将通过各种技术来检查警觉性，包括性能跟踪和脑电图活动检查。这项实验的结果不仅将从根本上改变我们对光如何影响人类昼夜节律起搏器的看法，而且还将为治疗昼夜节律紊乱带来直接的、可测试的治疗方法。它还可能导致更好地理解光对下丘脑影响的其他功能的影响，包括情绪和内分泌功能。 公共卫生相关性：内部生物钟与外部世界之间缺乏同步越来越成为我们全天候生活中的一个重要问题，并导致严重的负面健康后果，包括癌症风险增加，工作场所事故和肥胖。事实上，国际癌症研究机构，世界卫生组织的癌症分支机构，将轮班工作列为可能的致癌物质。该项目旨在研究内部生物钟与外部世界同步的大脑生理学，并将测试一种同步这种大脑时钟的新方法，这种方法可能会为轮班工作者，喷气式飞机旅行者和青少年提供新的治疗方法。