Understanding the impact of environmental disruption in biological timing systems through signal processing.

通过信号处理了解环境破坏对生物计时系统的影响。

• 批准号: 9386306
• 负责人: Benjamin Lee Smarr
• 金额: $ 9.87万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9386306
• 关键词: Address; Adrenal Glands; Affect; Animals; Automobile Driving; Back; Behavioral; Biological; Biological Models; Body Temperature; Body Temperature Changes; Brain; Cells; Cellular Phone; Chronic; Circadian Rhythms; Corticosterone; Coupling; Cues; Darkness; Data; Development; Diabetes Mellitus; Disease; Dose; Dysmenorrhea; Dyspepsia; Endocrine; Endocrine system; Environment; Environmental Impact; Estradiol; Feedback; Female; Frequencies; Future; Genetic; Glucocorticoids; Health; Hormonal; Hormonal Change; Hour; Human; Hypothalamic structure; Impaired cognition; Impairment; Implant; Individual; Infertility; Inflammation; Investigation; Jet Lag Syndrome; Life; Light; Lighting; Machine Learning; Malignant Neoplasms; Mammals; Measures; Mental Depression; Modeling; Modernization; Monitor; Myocardial Infarction; Obesity; Operative Surgical Procedures; Organ; Orphan; Output; Ovulation; Pattern; Periodicity; Persons; Pharmacology; Phase; Physiological; Physiology; Pituitary-Adrenal System; Planet Earth; Pollution; Prevention strategy; Preventive treatment; Rattus; Records; Regulation; Research Infrastructure; Resolution; Risk; Risk Marker; Sampling; Schools; Shapes; Signal Transduction; Social Obligations; Spermatogenesis; Stress; Stroke; Structure; System; Testing; Testosterone; The Sun; Time; Tissues; Wireless Technology; Work; base; biological systems; body system; comparative; drinking; feeding; high risk; male; mathematical model; minimally invasive; pituitary gonadal axis; predicting response; predictive modeling; rapid detection; reconstruction; resilience; response; shift work; signal processing; social; suprachiasmatic nucleus; targeted treatment; temporal measurement; time use

Project Summary/Abstract. Life on Earth evolved to take time cues from the Sun. Consequently, most or all cells in the mammalian body use genetic feedback loops to time their daily (circadian) rhythms. When a person or any mammal sees light, that winds an orchestrating circadian brain clock in the hypothalamic suprachiasmatic nucleus (SCN). The SCN in turn helps keep the myriad other tissue and endocrine rhythms in synchrony, enabling health. The modern environment is highly disruptive to this internal synchrony. Light at night from cell phones or urban light pollution, and social impositions like school start times or rotating work shifts all act as “temporal pollution,” causing loss of internal synchrony. The more severe the desynchrony, the higher the risk for a broad range of diseases, including obesity, cancer, infertility, depression and ultimately cognitive decline. Without knowing how these systems normally maintain synchrony or which systems are normally synchronized, it is hard to understand what happens in desynchrony to degrade health. This problem is complicated by the fact that some biological systems have ultradian (every few hours) and infradian (every few days) cycles in addition to circadian cycles. The hypothalamo-pituitary-adrenal axis (HPA) generates ultradian rhythms through negative feedback, but also shows a strong circadian cycle; the hypothalamo-pituitary-gonadal axis (HPG) shows the same negative feedback ultradian activity, circadian rhythmicity, and also infradian rhythms of ovulation and spermatogenesis. These two axes are regulated by the SCN. Recent work indicates that there is cross-talk between these axes, and that their hormonal outputs - corticosterone, and estradiol (in females) and testosterone (in males), respectively – work to synchronize extra-SCN tissues and behavioral rhythms of feeding and drinking (FaD). Finally, the SCN, HPA, and HPG axes all affect core body temperature (CBT), so that high temporal resolution recordings of CBT contain information about the cycling and synchrony of these systems across time scales. There are three aims to this proposal, using rats as a model system: 1) Test at high temporal resolution the effects of changes to the HPA axis, HPG axis, and SCN on CBT. 2) Use these relationships to build a model that can back-predict the state of the HPA axis, HPG axis, and SCN from a high temporal resolution CBT record of a given individual. 3) Expose rats to environmental temporal disruption in the form of a 6 h “jetlag” phase advance of the light cycle, and use the model to predict the response across these systems at 1-minute temporal resolution. This work will employ within-animal comparisons before and after surgical and pharmacological manipulations of rats whose FaD, activity, and CBT are captured continuously at 1-minute resolution. These data will be analyzed using signal-processing and machine learning to define patterns and relationships. The resulting model will allow minimally-invasive exploration of environmental disruption across physiological systems in real time. The model will be used to quantify synchrony as it is disrupted and re-emerges, identifying markers for risk or resilience, and generating hypotheses for future work into preventive strategies and treatments.

项目摘要/摘要。 地球上的生命从太阳开始发展。 使用遗传反馈循环为他们的日常（昼夜节律）节奏计时。 这会在下丘脑上的核心（SCN）中串行昼夜节律时钟 反过来，有助于保持无数的组织和内分泌节奏，从而使健康。 环境对这种内部同步高度破坏。 和社会强加的学校起步时间或旋转工作之类 内部同步。 包含肥胖，癌症，不育，深度和最终认知能力下降。 系统通常保持同步或哪些系统正常同步，很难理解什么 发生在降解健康的情况下发生的事实。 除了每隔几天）和昼夜节日外，有超级（每隔几天）（每隔几天） 下丘脑 - 垂体 - 肾上腺轴（HPA）通过负反馈产生超级节奏，但也会产生 显示强烈的苏联周期； 反馈超级活性，昼夜节律以及卵形和精子发生的基础节奏。 这两个轴由SCN调节。 并且激素输出 - 皮质酮和雌二醇（在女性中）和睾丸酮（在男性中）， 分别进行同步的额外SCN组织和进食和饮酒的行为节奏（FAD）。 最后，SCN，HPA和HPG轴轴轴都会影响核心身体身体身体（CBT），因此高度分辨率很高 CBT的记录包含有关系统跨时间尺度的循环和同步的信息。 该提议有三个目标 对HPA轴，HPG轴和SCN的变化对CBT的影响。 可以从高临时CBT记录中进行后预测HPA轴，HPG轴和SCN的状态 给定的个人。 光周期，并使用模型在1分钟时间内预测整个系统的响应 解决方案。 在1分钟的分辨率下连续捕获对大鼠FAD，活动FAD和CBT的操纵 将使用信号处理和机器学习来定义模式和关系 模型将允许对真实生理系统之间环境破坏的最小侵入性探索 时间。 或韧性，并为未来的工作产生假设，以进行预防策略和治疗。