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

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 社会互动对动物健康至关重要。与社会环境的长期隔离 影响动物的行为、生理和健康，在新冠肺炎大流行期间表现为 睡眠障碍和饮食紊乱的程度，以及其他全人群的行为问题。这个 慢性社会隔离被处理并对健康至关重要的潜在机制 行为是未知的。与社会环境短暂的脱离并不是有害的。社会孤立，由 它的本质，是一个持续和漫长的过程，然而动物的大脑是如何构建一个进化状态的 记录这一过程仍然是从生物学角度理解社会隔离的一个突出问题。至 为了应对这一挑战，我建立了一个黑腹果蝇模型，并发现了分子 与急性和慢性社交隔离相关的生理状态之间的差异。这部小说 该方法通过使用“隔离定时”作为参数来实现对底层机制的剖析， 从而允许在任何情况下第一次识别发出长期社会隔离状态的细胞 模型系统。我之前的研究表明，操纵已识别的细胞会改变人们对 社会隔离持续时间和社会隔离导致的行为结果，包括睡眠不足和 吞噬过多。在这项提案中，我们计划实施三个免费项目，这些项目利用我们最近的 结果进一步揭示了慢性社交中调节生理效应的守时机制 与世隔绝。首先，我们将阐明基因和分子途径有助于守时和 调解由慢性社会隔离引起的对健康至关重要的行为改变，特别关注 与生物钟的串音。其次，我们将确定“隔离”背后的分子底物 在慢性社交隔离期间的时间安排，并询问“隔离计时器”如何发出睡眠/唤醒调节信号 网络。第三，我们将调查长期的社会隔离如何导致永无止境的饥饿和影响 新陈代谢。为了实现这些目标，我们将采用多学科方法，包括神经遗传学、高等 吞吐量和高分辨率行为测量、转录组分析、功能成像和 代谢组学分析。拟议的研究，使用一个创新的框架来研究机制，通过 哪些慢性社会隔离是在长时间范围内进行的，并影响到 分子和细胞水平，最终将导致对社会隔离生物学的更深层次的理解 以及可能的干预/治疗措施，以减轻长期社会孤立造成的痛苦和疾病。