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）：酒精中毒综合神经科学倡议（INIA）-西部联盟的首要目标是确定与扩展杏仁核及其连接相关的大脑奖励回路中发生的分子，细胞和行为神经适应。据推测，遗传差异和/或神经适应在这个电路是负责的个体差异的脆弱性过度饮酒。因此，我们的主要重点之一是识别其表达受酒精调节的基因，以及负责任何给定的过量饮酒模型的基因。Wu U 01是INIA-West Consortium的18个U 01之一，专注于从充分表征的饮酒动物模型中富集的脑组分的差异蛋白质组学分析，目的是鉴定与行为表型相关的基因靶标。最近，该联盟的集体努力集中在51个基因靶点上。我们建议扩大Wu U 01母基金的范围，以包括蛋白质组学服务组件（称为INIA-West定量蛋白质组学核心），以满足INIA-West的分析蛋白质组学需求。具体而言，将针对最近选定的51个INIA-West基因靶标中的每一个开发靶向蛋白质组学测定（“质谱Western”），并将用于定量来自INIA-West研究者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母基金申请的补充资金将为INIA-West提供一个集中的服务组件，将分析工作集中在INIA-West基因靶蛋白的定量上，并促进对多种动物模型和过度饮酒范例的比较分析。 公共卫生相关性：高通量多重测量选定的基因靶蛋白将加快理解潜在的脆弱性过度饮酒的分子差异。