Role of drosophila Neuropeptide F in Ethanol Response

果蝇神经肽 F 在乙醇反应中的作用

• 批准号: 6870408
• 负责人: PING SHEN
• 金额: $ 25.76万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6870408
• 关键词: Drosophilidae; arthropod genetics; behavior test; behavioral /social science research tag; biochemical evolution; biological signal transduction; drug resistance; drug tolerance; ethanol; ethology; gene expression; genetic manipulation; genetic models; genetic regulation; genetic screening; immunocytochemistry; neuroanatomy; neuropeptide Y; neuropeptides; neuropharmacology; neuroregulation; pharmacogenetics; protein structure function; psychobiology; psychopharmacology

DESCRIPTION (provided by applicant): The neuropeptide Y (NPY) signaling system is both structurally and functionally conserved between Drosophila and mammals. Recent studies from this laboratory have shown that Drosophila neuropeptide F (NPF), the single NPY homologue in the fly genome, plays important roles in modulating motivational feeding, locomotion and alcohol response. Parallel phenotypes have been observed between NPF-deficient flies and NPY-knockout mice: both animals displayed normal baseline feeding but deficits in motivational feeding; NPF-deficient fly larvae showed food-elicited hyperactive locomotion whereas NPY knockouts exhibited increased susceptibility to seizure; both NPF-deficient flies and NPY knockout mice displayed decreased ethanol sensitivity. Moreover, flies overexpressing NPF showed increased sensitivity to ethanol sedation, similar to the phenotypes of NPY-overexpressing mice. These observations strongly suggest that Drosophila is a suitable genetic model for the study of the neural, cellular and molecular mechanisms underlying the action the NPF/NPY signaling system. This proposed research aims to further elucidate the neurobiological basis of. NPY-mediated regulation of ethanol related behaviors. The specific aims of this application include: 1) Identification and functional analysis of the neuroanatomical sites of the NPF system involved in modulation of ethanol response; 2) EMS-mutagenesis screen of genes involved in NPF/NPFR1-mediated ethanol response; 3) gain-of-function screen for genes involved in NPF/NPFR1 -mediated ethanol response.. The results from these studies should provide novel insights into understanding why a common neural signaling system underlies the controls of feeding and alcohol related behaviors, what components of the signaling pathway are conserved, and how genetic factors contribute to ethanol sensitivity in diverse organisms

描述（由申请人提供）：神经肽Y（NPY）信号系统在果蝇和哺乳动物之间在结构和功能上都是保守的。该实验室最近的研究表明，果蝇神经肽 F (NPF) 作为果蝇基因组中的单一 NPY 同源物，在调节动机性进食、运动和酒精反应中发挥着重要作用。在 NPF 缺陷果蝇和 NPY 敲除小鼠之间观察到平行表型：两种动物都表现出正常的基线摄食，但动机摄食方面存在缺陷； NPF 缺陷的果蝇幼虫表现出食物引起的过度运动，而 NPY 敲除则表现出癫痫发作的易感性增加； NPF 缺陷果蝇和 NPY 敲除小鼠均表现出乙醇敏感性降低。此外，过表达 NPF 的果蝇对乙醇镇静的敏感性增加，与 NPY 过表达小鼠的表型相似。这些观察结果强烈表明，果蝇是研究 NPF/NPY 信号系统作用背后的神经、细胞和分子机制的合适遗传模型。 这项研究旨在进一步阐明神经生物学基础。 NPY 介导的乙醇相关行为调节。该应用的具体目标包括：1）对参与乙醇反应调节的 NPF 系统神经解剖位点进行识别和功能分析； 2) EMS诱变筛选参与NPF/NPFR1介导的乙醇反应的基因； 3）对参与NPF/NPFR1介导的乙醇反应的基因进行功能获得性筛选。这些研究的结果应该为理解为什么一个共同的神经信号系统是控制进食和酒精相关行为的基础、哪些组成部分提供新的见解信号通路的保守性，以及遗传因素如何影响不同生物体的乙醇敏感性