Center for Circadian Rhythms and Alcohol-Induced Tissue Damage

摘要 只有一部分酒精使用障碍患者会出现临床上显著的器官损伤（约10 - 10%）。 30%），但尚不清楚是什么因素使个体易患具有临床意义的器官病理学？ 有令人信服的证据支持这一假设，即昼夜动态平衡的破坏（例如，移位 工作、社会时差）是易受酒精引起的疾病影响的一个似乎合理的易感因素。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的障碍 节律和酒精引起的器官损伤一直缺乏一个结合昼夜节律和酒精 进行这些研究所需的专门知识以及建立 进行昼夜节律研究所需的基础设施。此R24酒精研究资源的目标 该计划旨在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将昼夜节律的研究 节奏融入他们现有的研究项目。为了实现这一目标，我们提出以下建议： 具体目标：目标1。提供必要的资源，以进行涉及酒精的新颖，创新的研究 和昼夜节律。我们的R24计划中拟议的基础设施、专业知识和人员将允许 酒精研究人员通过在我们的设施进行研究来调查创新的假设。结束时 在每项研究中，将向研究者提供其研究的生物标本，以评价研究特定的 结果。目标二。为了提供来自酒精喂养的昼夜节律紊乱的小鼠和昼夜节律紊乱的小鼠的生物标本， 人类饮酒我们的R24酒精研究资源计划将提供生物标本（从 我们的生物储存库）酒精研究人员调查假设使用标准化的实验 操作和评估。生物标本将来自已经进行的研究， 可供索取的标本，包括人类和小鼠标本。目标3.提供咨询 和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一个 通过提供昼夜节律方面的咨询和培训，为酒精研究界提供资源 研究（Aim 3a）和对其他实验室收集的数据进行昼夜节律特异性分析（Aim 3 b）。该NIAAA R24酒精研究资源计划的资源将促进科学严谨性， 在酒精和昼夜节律实验中的重复性。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了更深入的了解， 这将导致识别新的靶点和干预措施，以预防和治疗酒精诱导的器官损伤。 损害

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.