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: 7010346
• 负责人: PING SHEN
• 金额: $ 25.15万
• 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/7010346
• 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是保守的。该实验室的最新研究表明，果蝇神经肽F（NPF）是飞蝇基因组中的单个NPY同源物，在调节动机喂养，运动和酒精反应中起着重要作用。 NPF缺陷蝇和NPY敲除小鼠之间已经观察到平行表型：两种动物均表现出正常的基线喂养，但动机喂养的缺陷。 NPF缺乏的蝇幼虫显示出食物吸引的多动力运动，而NPY敲除表现出增加对癫痫发作的敏感性。 NPF缺陷蝇和NPY基因敲除小鼠均显示出降低的乙醇敏感性。此外，过表达NPF的苍蝇对乙醇镇静的敏感性增加，类似于表达NPY的小鼠的表型。这些观察结果强烈表明果蝇是研究NPF/NPY信号系统的神经，细胞和分子机制的合适遗传模型。 这项拟议的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。该应用程序的具体目的包括：1）鉴定和功能分析，对乙醇反应调节的NPF系统的神经解剖位点； 2）参与NPF/NPFR1介导的乙醇反应的基因的EMS-刺量筛选； 3）对NPF/NPFR1介导的乙醇反应的基因的功能屏幕。这些研究的结果应提供新的见解，以理解为什么常见的神经信号系统的控制是基于喂养和酒精相关行为的控制，以及信号途径的哪些成分以及遗传因素如何促进乙醇敏感性的乙醇敏感性。