Role of the circadian rhythm on endocannabinoid response to an acute stress

昼夜节律对急性应激内源性大麻素反应的作用

• 批准号: 10320481
• 负责人: Nicole P Bowles
• 金额: $ 18.1万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10320481
• 关键词: Acute; Adult; Affect; Age; Americas; Area; Arithmetic; Arousal; Attenuated; Behavior; Biological; Black American; Black Populations; Black race; Blood Platelets; Cardiac; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Cessation of life; Characteristics; Circadian Rhythms; Communities; Cues; Depressed mood; Development; Doctor of Philosophy; Emotional; Emotions; Endocannabinoids; Environment; Enzymes; Etiology; Event; Evidence based intervention; Exercise; Exertion; Expenditure; Future; Goals; Health; Heart Diseases; Heart Rate; Hemostatic function; Human; Hydrocortisone; Hypertension; Incidence; Intervention; Knowledge; Labor Forces; Laboratories; Lead; Light; Lighting; Link; Lipids; Marshal; Measures; Medical; Medication Management; Melatonin; Mentors; Moderate Exercise; Moods; Mus; Pathway interactions; Periodicity; Phase; Physiological; Physiology; Plasma; Prevention; Protocols documentation; Psyche structure; Psychosocial Stress; Questionnaires; Race; Recovery; Reporting; Research; Rest; Risk; Role; Salivary; Schedule; Scientist; Sleep; Sleep Wake Cycle; Standardization; Stress; Stroke; System; Testing; Time; Training; Translating; Variant; Wakefulness; Work; acute stress; aged; awake; base; biological adaptation to stress; cardiometabolism; cardioprotection; cardiovascular health; career; caucasian American; circadian; cost; emotion regulation; endocannabinoid signaling; endogenous cannabinoid system; habituation; improved; mortality; parent grant; platelet function; productivity loss; psychosocial; receptor; response; shift work; stress management; stress reactivity; stressor

Project Summary Cardiovascular (CV) disease is the leading cause of death in the US. Night and rotating shift work, ~20% of the labor force, is associated with a greater incidence of both psychosocial stress and CV disease suggesting that wakefulness and activity when the body is optimized for sleep and recovery is harmful to one’s health. Acute stressors in the form of both heightened emotions in response to a psychosocial stress and moderate exercise can trigger a CV event, however, the underlying physiology remains unclear. Endocannabinoids (eCB) are lipid messengers that modulate the emotional and physiological response to stress and have also been demonstrated to regulate CV function. Colleagues and I have recently demonstrated a robust endogenous circadian rhythm in basal levels of circulating eCBs with a trough during the biological night. However, the circadian variation in eCB reactivity, change from baseline in response to an acute stress, remains unclear. A difference in eCB response and associated CV reactivity to an acute stress across the circadian system provides a plausible pathway that could underlie risks for development of CV disease in shift workers. Thus, I aim to test the hypotheses that changes of circulating eCBs in response to (a) an acute psychosocial stress and (b) a mild somatic stress (exercise) are dependent upon circadian phase and will correlate with changes in emotional and CV reactivity. The proposed research will take advantage of the opposite effects on mood of psychosocial stress (depressed mood) and exercise stress (improved mood) to further examine how eCB regulation of emotional processing is related to CV function. Additionally, as Black Americans have the highest age-adjusted CV disease mortality and persistently demonstrate differential responses to stress this proposal will test the hypothesis that Blacks compared to Whites will have attenuated eCB responses to psychosocial and somatic stressors. These aims will be achieved via a multi-day circadian protocol (dim lighting free of time cues) with sleep-wake cycles adjusted to recurring 18h cycles so that after numerous cycles all behaviors occur evenly across all circadian phases. Assessments include circadian phase and amplitude from salivary melatonin, circulating eCBs from blood plasma and mood from questionnaires. Relevant markers of CV function will include autonomic function and markers of hemostasis. This protocol will be performed in 40 healthy adults as an additional component to my primary mentor’s active project (R01HL142064, PI, Steven Shea). Elucidation of mechanisms that impact stress reactivity across the circadian system integrates my prior training and is a logical progression in my research career that will provide valuable information for evaluating the utility of evidence-based interventions. To achieve my long-term goal of becoming an independent scientist translating stress and circadian research between the laboratory and community, this K01 will provide further training in the following areas: 1) Standardization and assessment of stress protocols; 2) Advanced statistical training for examining the temporal order of stress markers; and 3) Knowledge on the etiology and prevention of sudden CV events and assessment of CV health.

项目摘要 心血管（CV）疾病是美国死亡的主要原因。夜间和旋转的班次工作，约有20％ 劳动力与心理压力和简历疾病的更大事件有关，表明 当身体对睡眠和恢复进行优化时，清醒和活动对人的健康有害。急性 响应社会心理压力和适度运动的情绪增强的形式的表现 可以触发简历事件，但是，潜在的生理尚不清楚。内源性大麻素（欧洲央行）是脂 调节压力的情感和身体反应的使者也已被证明 调节简历函数。我和我最近在 在生物之夜，循环ECB的基本水平。但是，欧洲央行的昼夜节律变化 反应性，从基线响应急性应力的变化尚不清楚。欧洲央行响应的差异 并相关的对昼夜节律急性应激的CV反应性提供了一个合理的途径 转变工人中CV疾病发展的风险可能是基础。那我的目的是检验 响应（a）急性社会心理压力和（b）轻度躯体压力的循环ECB的变化 （锻炼）取决于昼夜节律，并将与情绪和简历反应性的变化相关。 拟议的研究将利用对心理压力情绪的相反影响（沮丧 情绪）和运动压力（改善情绪），以进一步研究欧洲央行的情感处理调节 与CV功能有关。此外，由于黑人美国人的年龄调整后的简历疾病死亡率最高， 持续证明对压力的差异反应该提议将检验黑人的假设 与白人相比，将减弱欧洲央行对社会心理和躯体压力源的反应。这些目标会 可以通过调整睡眠效果周期来通过多天的昼夜节律协议（无时间提示）来实现 为了重复出现的18H循环，以使许多循环在所有昼夜节律阶段均匀地发生。 评估包括昼夜节期和唾液褪黑激素的放大器，从血液中循环ECB 问卷的等离子体和情绪。简历功能的相关标记将包括自主功能，并且 止血的标记。该方案将在40名健康成年人中进行，作为我的附加组成部分 主要导师的活动项目（R01HL142064，PI，Steven Shea）。阐明影响压力的机制 整个昼夜节律系统的反应性整合了我的先前培训，这是我的研究中的逻辑进步 将为评估基于证据的干预措施的实用性提供宝贵信息的职业。实现 我成为一名独立科学家的长期目标，将压力和昼夜节律转化为 实验室和社区，该K01将在以下领域提供进一步的培训：1）标准化和 评估压力方案； 2）检查临时压力顺序的高级统计培训 标记； 3）关于病因和预防突然简历事件的知识以及对简历健康的评估。