Interdisciplinary Studies for Mechanisms Underlying Social Isolation-Induced Health Critical Behavior Changes

社会隔离引起的健康关键行为变化背后机制的跨学科研究

• 批准号: 10713755
• 负责人: Wanhe Li
• 金额: $ 37.55万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713755
• 关键词: Acute; Address; Affect; Animal Behavior; Animals; Behavior; Behavioral; Biological; Biological Models; Biology; Brain; COVID-19 pandemic; Cells; Chronic; Chronic stress; Disease; Dissection; Drosophila melanogaster; Eating Disorders; Functional Imaging; Genetic; Goals; Health; Hunger; Hyperphagia; Interdisciplinary Study; Intervention; Mediating; Metabolism; Modeling; Molecular; Molecular Biology; Nature; Pathway interactions; Physiological; Physiology; Population; Problem behavior; Process; Research; Resolution; Signal Transduction; Sleep; Sleep Deprivation; Sleep disturbances; Social Environment; Social Interaction; Social Perception; Social isolation; Social status; Time; behavior change; behavior measurement; behavioral outcome; circadian pacemaker; innovation; insight; interdisciplinary approach; metabolomics; neurogenetics; novel; novel strategies; transcriptomic profiling; Acute; Address; Affect; Animal Behavior; Animals; Behavior; Behavioral; Biological; Biological Models; Biology; Brain; COVID-19 pandemic; Cells; Chronic; Chronic stress; Disease; Dissection; Drosophila melanogaster; Eating Disorders; Functional Imaging; Genetic; Goals; Health; Hunger; Hyperphagia; Interdisciplinary Study; Intervention; Mediating; Metabolism; Modeling; Molecular; Molecular Biology; Nature; Pathway interactions; Physiological; Physiology; Population; Problem behavior; Process; Research; Resolution; Signal Transduction; Sleep; Sleep Deprivation; Sleep disturbances; Social Environment; Social Interaction; Social Perception; Social isolation; Social status; Time; behavior change; behavior measurement; behavioral outcome; circadian pacemaker; innovation; insight; interdisciplinary approach; metabolomics; neurogenetics; novel; novel strategies; transcriptomic profiling

Project Summary Social interactions are essential for animal health. Prolonged isolation from social environments profoundly affects animal behavior, physiology, and wellness, expressed during the COVID-19 pandemic as increased levels of sleep disruption and eating disorders, among other population-wide behavioral problems. The underlying mechanisms through which chronic social isolation is processed and impacts health-critical behavior are unknown. A brief disconnection from the social environment is not detrimental. Social isolation, by its very nature, is a continuous and prolonged process, yet how animal brain constructs an evolving state recording this process remains an outstanding problem in understanding social isolation biologically. To address this challenge, I established a Drosophila melanogaster model and discovered the molecular differences between physiological states associated with acute and chronic social isolation. This novel approach has enabled the dissection of underlying mechanisms by using “isolation timing” as a parameter, thereby allowing the identification of cells that signal the chronic status of social isolation for the first time in any model system. My previous research has shown that manipulating the identified cells alters the perception of social isolation duration and social isolation-induced behavioral outcomes, including sleep loss and hyperphagia. In this proposal, we plan to carry out three complimentary projects that capitalize on our recent results to further uncover the timekeeping mechanism modulating physiological effects during chronic social isolation. First, we will elucidate the genetic and molecular pathways that contribute to timekeeping and mediate health-critical behavioral alterations induced by chronic social isolation, with a special focus on the cross talk with the circadian clock. Second, we will identify the molecular substrates underlying “isolation timing” during chronic social isolation and interrogate how an “isolation timer” signals the sleep/wake regulatory network. Third, we will investigate how chronic social isolation drives insatiable hunger and impacts metabolism. To achieve these goals, we will employ a multidisciplinary approach including neurogenetics, high throughput and high-resolution behavioral measurements, transcriptome profiling, functional imaging, and metabolomic analysis. The proposed study, using an innovative framework to investigate the mechanisms by which chronic social isolation is processed on long-time scales and impacts health-critical behaviors at the molecular and cellular levels, will ultimately lead to a deeper understanding of the biology of social isolation and potential interventions/treatments to alleviate the suffering and diseases caused by chronic social isolation.

项目摘要 社会互动对于动物健康至关重要。从社会环境中长期隔离 影响在Covid-19大流行期间表达的动物行为，生理和健康，随着增加 睡眠中断和饮食失调的水平以及其他人口的行为问题。这 处理慢性社会隔离并影响健康关键的基本机制 行为未知。与社会环境的短暂脱节并不有害。社会隔离，由 它的本质是一个连续而延长的过程，但动物脑如何构建不断发展的状态 记录这一过程仍然是在生物学上理解社会隔离的一个重大问题。到 应对这一挑战，我建立了果蝇模型并发现了分子 与急性和慢性社会隔离相关的物理状态之间的差异。这本小说 方法已通过使用“隔离时间”作为参数，使基本机制的解剖， 从而允许识别任何第一次在任何人中向社会隔离的慢性状态发出的鉴定 模型系统。我以前的研究表明，操纵已确定的细胞会改变对 社会隔离持续时间和社会隔离引起的行为结果，包括睡眠损失和 脾气。在此提案中，我们计划进行三个免费的项目，以利用我们的最新 结果可以进一步揭示定时机制调节慢性社会期间生理效应的结果 隔离。首先，我们将阐明有助于计时的遗传和分子途径 调解由慢性社会隔离引起的关键健康行为改变，特别关注 与昼夜节律聊天。其次，我们将确定“隔离”的分子底物 时间”在长期社会隔离期间，并询问“隔离计时器”如何标志着睡眠/唤醒调节性 网络。第三，我们将调查长期的社会隔离如何驱动无限的饥饿和影响 代谢。为了实现这些目标，我们将采用一种多学科方法，包括神经遗传学，高 吞吐量和高分辨率的行为测量，转录组分析，功能成像和 代谢组分析。拟议的研究使用创新框架来研究 长期以长期处理的慢性社会隔离，并影响了关键的健康行为 分子和细胞水平，最终将使人们对社会隔离的生物学有更深入的了解 以及潜在的干预措施/治疗，以减轻由长期社会隔离引起的痛苦和疾病。