Proteomic Dissection of Withdrawal-Induced Excessive Drinking

戒断引起的过度饮酒的蛋白质组学解析

• 批准号: 7814528
• 负责人: Christine C Wu
• 金额: $ 8.72万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7814528
• 关键词: Alcohol consumption; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Amygdaloid structure; Animal Model; Animals; Antibodies; Area; Behavior; Behavioral; Biological Assay; Brain; Brain region; Breeding; Chronic; Cluster Analysis; Data; Dependence; Detection; Development; Dissection; Drosophila inturned protein; Equipment; Fractionation; Funding; Future; Gene Expression; Gene Targeting; Genes; Genetic; Genetic Models; Genotype; Goals; Growth; Heart; Heavy Drinking; Individual; Individual Differences; Informatics; Knock-out; Label; Letters; Longitudinal Studies; Mass Spectrum Analysis; Measurement; Metabolic; Methodology; Modeling; Molecular; Monitor; Mus; Mutagenesis; National Center for Research Resources; National Heart, Lung, and Blood Institute; Neurosciences; Parents; Phenotype; Procedures; Protein Isoforms; Proteins; Proteomics; RNA Interference; Reaction; Relapse; Research; Research Personnel; Resources; Rewards; Sampling; Services; Subcellular Fractions; Technology; Technology Transfer; Time; Tissues; Transgenic Animals; Transgenic Model; Transgenic Organisms; Validation; Western Blotting; Withdrawal; adenylyl cyclase 7; alcohol exposure; assay development; behavior test; brain tissue; comparative; drinking; drinking behavior; instrument; instrumentation; knockout animal; meetings; neuroadaptation; parent grant; preference; programs; protein expression; protein profiling; public health relevance; tool; validation studies

DESCRIPTION (provided by applicant): The overarching goal of the Integrative Neuroscience Initiative on Alcoholism (INIA)-West Consortium is to identify the molecular, cellular, and behavioral neuroadaptations that occur in the brain reward circuits associated with the extended amygdala and its connections. It is hypothesized that genetic differences and/or neuroadaptations in this circuitry are responsible for the individual differences in vulnerability to the excessive consumption of alcohol. Therefore, one of our main focuses is the identification of genes whose expression is regulated by alcohol and which are responsible for any given model of excessive alcohol consumption. The Wu UOl is one 18 U01s of the INIA-West Consortium and is focused on the differential proteomic analysis of brain fractions enriched from well-characterized animal models of drinking for the purpose of identifying gene targets associated with the behavioral phenotype. Recently, the collective efforts of the Consortium have converged on 51 gene targets. We propose to expand the scope of the Wu U01 parent grant to include a proteomic service component (to be referred to as the INIA-West Quantitative Proteomics Core) to meet the analytical proteomic needs of INIA-West. Specifically, targeted proteomic assays ("mass spectrometry Westerns") will be developed for each of the recently selected 51 INIA-West gene targets and will be used to quantify these targets in brain samples generated from the INIA-West investigators. Currently, INIA-West has no designated Proteomics Core Resource and no mechanism for the proteomic analyses of INIA-West samples. This request for supplementary funds through the Wu UOl parent grant will provide a centralized service component to INIA-West to focus analytical efforts on the quantification of INIA-West gene target proteins and facilitate comparative analyses across the multiple animal models and paradigms of excessive drinking. PUBLIC HEALTH RELEVANCE: High-throughput multiplexed measurements of selected gene target proteins will expedite the understanding of molecular differences underlying the vulnerability to excessive alcohol consumption.

描述（由申请人提供）：酗酒综合神经科学倡议（INIA）-西方联盟的总体目标是确定与扩展杏仁核及其连接相关的大脑奖赏回路中发生的分子、细胞和行为神经适应。据推测，该回路中的遗传差异和/或神经适应是造成过度饮酒易感性的个体差异的原因。因此，我们的主要关注点之一是鉴定其表达受酒精调节的基因，这些基因与任何特定的过度饮酒模型有关。 Wu UOl 是 INIA-West 联盟的 18 U01 之一，专注于对从充分表征的饮酒动物模型中丰富的大脑部分进行差异蛋白质组分析，目的是识别与行为表型相关的基因目标。最近，该联盟的集体努力已集中在51个基因目标上。我们建议扩大 Wu U01 母基金的范围，纳入蛋白质组服务组件（称为 INIA-West 定量蛋白质组核心），以满足 INIA-West 的分析蛋白质组需求。具体来说，将为最近选择的 51 个 INIA-West 基因靶标中的每一个开发靶向蛋白质组测定（“质谱 Westerns”），并将用于量化 INIA-West 研究人员生成的大脑样本中的这些靶标。目前，INIA-West 没有指定的蛋白质组学核心资源，也没有对 INIA-West 样品进行蛋白质组学分析的机制。通过 Wu UOl 母基金申请补充资金将为 INIA-West 提供集中服务组件，以将分析工作集中在 INIA-West 基因目标蛋白的量化上，并促进多种动物模型和过度饮酒范例的比较分析。 公共健康相关性：对选定基因靶蛋白的高通量多重测量将加快对导致过度饮酒脆弱性的分子差异的理解。