Mechanisms underlying ethanol action in Drosophila

果蝇中乙醇作用的机制

• 批准号: 6937973
• 负责人: NANCY L URIZAR
• 金额: $ 4.37万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-31 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6937973
• 关键词: Drosophilidae; RNA binding protein; alcoholism /alcohol abuse; brain mapping; cytoskeletal proteins; drug metabolism; drug tolerance; ethanol; gene expression; genetically modified animals; immunocytochemistry; in situ hybridization; invertebrate locomotion; learning disorders; memory disorders; microarray technology; mutant; neuropeptides; neuropharmacology; phenotype; postdoctoral investigator; protein structure function; psychopharmacology

DESCRIPTION (provided by applicant): The goal of this proposal is to elucidate the molecular mechanisms underlying ethanol action in the Drosophila brain. Towards this end I have developed an assay system for acute and chronic tolerance to the sedative effects of ethanol. Using this assay and microarrays, I have identified several genes that exhibit a change in gene expression upon acute and/or chronic exposure to ethanol. Homer, a putative scaffolding protein, and Ypsilon Schachtel (YPS), an RNA binding protein were chosen for further characterization. Preliminary data show that Drosophila mutants of the Homer and YPS genes exhibit decreased and increased ethanol sensitivity, respectively, suggesting that Homer and YPS mediate some of the behavioral effects of ethanol. To determine whether Homer and YPS play a role in regulating ethanol sensitivity and tolerance in Drosophila, the following aims will be pursued: 1) Determine whether the ethanol phenotypes observed in Homer and YPS mutant flies can be rescued using Homer or YPS genomic constructs. 2) Determine whether the ethanol phenotypes observed in the Homer and YPS mutant flies are the result of a change in ethanol absorption/metabolism. 3) Identify the Homer and YPS spatial and temporal expression requirements for rescue of the ethanol phenotypes using the GAL4/UAS and TARGET systems. 4) Determine whether mutants of Homer and YPS have defects in learning and memory and/or locomotor activity.

描述（由申请人提供）：该提案的目标是阐明果蝇大脑中乙醇作用的分子机制。为此，我开发了一种对乙醇镇静作用的急性和慢性耐受性的测定系统。使用这种测定和微阵列，我已经鉴定了几个在急性和/或慢性接触乙醇时表现出基因表达变化的基因。选择 Homer（一种假定的支架蛋白）和 Ypsilon Schachtel（YPS）（一种 RNA 结合蛋白）进行进一步表征。初步数据显示，Homer 和 YPS 基因的果蝇突变体分别表现出乙醇敏感性降低和增加，这表明 Homer 和 YPS 介导了乙醇的一些行为效应。为了确定 Homer 和 YPS 是否在调节果蝇乙醇敏感性和耐受性中发挥作用，将追求以下目标：1）确定在 Homer 和 YPS 突变果蝇中观察到的乙醇表型是否可以使用 Homer 或 YPS 基因组构建体来挽救。 2) 确定在 Homer 和 YPS 突变果蝇中观察到的乙醇表型是否是乙醇吸收/代谢变化的结果。 3) 确定使用 GAL4/UAS 和 TARGET 系统拯救乙醇表型的 Homer 和 YPS 空间和时间表达要求。 4)确定Homer和YPS突变体是否存在学习记忆和/或运动活动缺陷。