Center for Circadian Rhythms and Alcohol-Induced Tissue Damage

摘要 只有一部分有酒精使用障碍的人会出现临床上严重的器官损害(~10- 30%)，但目前尚不清楚是什么因素使个人易患上具有临床意义的器官病理？ 有令人信服的证据支持这样一种假设，即昼夜节律稳态的破坏(例如，改变 工作、社交时差)似乎是易受酒精引起的病症影响的易感因素。对以下项目感兴趣 对昼夜节律的研究正在增长；然而，研究昼夜节律之间的相互作用是一个障碍 节律和酒精引起的器官损害是缺乏昼夜节律和酒精的组合 进行这些研究所需的专业知识，以及建立 进行昼夜节律研究所需的基础设施。R24酒精研究资源的目标 计划是通过提供必要的基础设施、支持和专业知识来克服这些障碍 将允许美国和国际上的酒精研究人员纳入对昼夜节律的研究 在他们现有的研究计划中加入节奏。为了实现这一目标，我们提出如下建议 具体目标：目标1.提供必要的资源，开展有关酒精的新颖、创新的研究 和昼夜节律。我们R24计划中建议的基础设施、专业知识和人员将允许 酒精研究人员通过在我们的设施中进行研究来调查创新假说。在结束时 在每项研究中，将向研究人员提供他们研究中的生物标本，以评估特定于研究的 结果。目的2.从酒精喂养、昼夜节律紊乱的小鼠和昼夜节律紊乱的小鼠中提供生物标本 饮酒的人类。我们的R24酒精研究资源计划将提供生物样品(来自 我们的生物库)提供给酒精研究人员，以使用标准化实验来研究假说 操纵和评估。这些生物素将来自已经进行的研究和 可供索取的标本包括人和小鼠标本。目标3.提供咨询 以及用于昼夜节律研究的分析工具。我们的R24酒精研究资源计划将是 通过提供昼夜节律方面的咨询和培训，为酒精研究社区提供资源 研究(目标3a)和对其他实验室收集的数据进行特定昼夜节律分析(目标3a) 3B)。NIAAA R24酒精研究资源计划的资源将促进科学严谨性和 酒精和昼夜节律实验中实验室间的重复性。预计这些努力将导致 对每个器官中重叠或不同的疾病机制有更大的了解 这将导致确定预防和治疗酒精诱导器官的新靶点和干预措施 损坏。

ABSTRACT Only a subset of individuals with an alcohol-use disorder develop clinically significant organ damage (~10- 30%) but it is not known what factors predispose individuals to develop clinically significant organ pathology? There is compelling evidence to support the hypothesis that disruption of circadian homeostasis (e.g., shift work, social jet lag) is a plausible susceptibility factor for vulnerability to alcohol-induced pathologies. Interest in the study of circadian rhythms is growing; however, an obstacle to study the interactions between circadian rhythms and alcohol-induced organ damage has been the lack of a combined circadian rhythm and alcohol expertise that is required to conduct these studies as well as the high cost associated with establishing the infrastructure necessary to perform circadian research. The objective of this R24 Alcohol Research Resource Program is to overcome these obstacles by providing the necessary infrastructure, support, and expertise that will allow both alcohol researchers in the United States and internationally to incorporate the study of circadian rhythms into their existing research programs. In order to achieve this objective we propose the following Specific Aims: Aim 1. Provide the essential resources to conduct novel, innovative studies involving alcohol and circadian rhythms. The proposed infrastructure, expertise and personnel in our R24 Program will allow alcohol researchers to investigate innovative hypotheses by conducting studies in our facility. At the conclusion of each study, investigators will be provided with biospecimens from their study to evaluate study-specific outcomes. Aim 2. To provide biospecimens from alcohol-fed, circadian disrupted mice and circadian disrupted humans consuming alcohol. Our R24 Alcohol Research Resource Program will provide biospecimens (from our biorepository) to alcohol researchers to investigate hypotheses using standardized experimental manipulations and assessments. The biospecimens will be from studies that have already been conducted and those that are available for request including both human and mouse specimens. Aim 3. Provide consultation and analytic tools for circadian rhythm research. Our R24 Alcohol Research Resource Program will be a resource for the alcohol research community by providing consultation and training in circadian rhythms research (Aim 3a) and by conducting circadian-specific analyses of data collected in other laboratories (Aim 3b). The resources of this NIAAA R24 Alcohol Research Resource Program will facilitate scientific rigor and reproducibility across labs in alcohol and circadian rhythm experimentation. These efforts are expected to lead to a significantly greater understanding of the overlapping or dissimilar disease mechanisms in each organ which should lead to identification of novel targets and interventions to prevent and treat alcohol-induced organ damage.