Mechanisms of alcohol-induced plasticitey mediated by Arf6
Arf6介导的酒精诱导可塑性机制
基本信息
- 批准号:9761413
- 负责人:
- 金额:$ 34.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-10 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAlcohol abuseAlcohol consumptionAlcohol dependenceAlcoholsBehavioralBehavioral AssayBiochemicalBiological AssayBrainCell Culture TechniquesCell Surface ReceptorsCellsChronicConsumptionCouplingDataDependenceDevelopmentDiseaseDoseDrosophila genusEndocytosisEthanolExperimental GeneticsFDA approvedFRAP1 geneFaceFamilyGTPase-Activating ProteinsGene FamilyGenesGoalsGrowthGuanineGuanine Nucleotide Exchange FactorsGuanosine Triphosphate PhosphohydrolasesHealth HazardsHumanInsulin ReceptorLaboratoriesLeadMediatingMediationMetabolismMolecularMonomeric GTP-Binding ProteinsNervous system structureNeuronal PlasticityNeuronsOutcomePathway interactionsPharmaceutical PreparationsPharmacologyPlayPublishingRattusReactionReceptor SignalingRelapseResearchResistanceRibosomal Protein S6 KinaseRisk FactorsRodentRoleSedation procedureSelf AdministrationSignal TransductionSirolimusTestingTherapeutic InterventionUnited StatesUp-RegulationVertebratesaddictionadverse outcomealcohol abuse therapyalcohol behavioralcohol exposurealcohol responsealcohol sensitivityalcohol use disorderbasebehavioral outcomebehavioral responseeffective therapyexperienceflygenetic manipulationhigh risk drinkingin vivoinsightinsulin mediatorsinsulin signalingmTOR Inhibitorneural circuitneuromechanismnew therapeutic targetnovelpreferencepreventreceptor-mediated signalingrhotargeted treatmenttherapeutic targettraffickingtranslational impactvinegar fly
项目摘要
Alcohol abuse disorders (AUD) are a major health hazard that affects millions of people every year in the
United States. Repeat alcohol exposure can lead to tolerance, increased preference and consumption. Such
behavioral changes, and the accompanying neuronal plasticity, underlie addiction, yet many molecular
mechanisms governing these changes remain to be elucidated. Signaling through the insulin receptor (InR) in
neurons is known to modify plasticity, but its effects on alcohol-induced behavioral responses are not known.
Our goal is to understand the cellular, neural, and circuit mechanisms of Arf6-dependent nervous system InR
signaling in alcohol-induced plasticity. This is based on our published data that Arf6 mediates InR signaling in
vivo and in cell culture. First, we will determine the mechanisms of Arf6-mediated InR signaling and
endocytosis. We will systematically, and comprehensively test the role of two gene families known to directly
regulate the function of Arf6. Second, we will determine neural circuits that specifically affect ethanol-induced
tolerance and consumption preference, as well as the naïve aversive reactions to alcohol. We will test the role
of Arf6 regulators in these circuits in alcohol-induced behavioral responses. Third, we will determine in vivo
mechanisms how signaling from the InR pathway can affect distinct alcohol-induced behavioral changes:
tolerance, and consumption preference. The genes we propose to investigate are all conserved from
Drosophila to humans, and the proposed research will advance our molecular understanding of the
mechanisms regulating alcohol-induced behavioral changes. This in turn, will result in the identification of new
risk factors and therapeutic targets for the treatment of alcohol abuse disorders.
酒精滥用障碍 (AUD) 是一种主要的健康危害,每年影响数百万人。
美国。重复接触酒精会导致耐受性、偏好和消费增加。
行为变化以及伴随的神经元可塑性是成瘾的基础,但许多分子
控制这些变化的机制仍有待阐明。
众所周知,神经元可以改变可塑性,但它对酒精引起的行为反应的影响尚不清楚。
我们的目标是了解 Arf6 依赖性神经系统 InR 的细胞、神经和回路机制
这是基于我们发表的数据,即 Arf6 在酒精诱导的可塑性中介导 InR 信号传导。
首先,我们将确定 Arf6 介导的 InR 信号传导和细胞培养的机制。
我们将系统地、全面地测试已知直接作用的两个基因家族的作用。
其次,我们将确定专门影响乙醇诱导的神经回路。
我们将测试其作用。
第三,我们将在体内确定这些回路中 Arf6 调节剂的作用。
InR 通路的信号传导如何影响酒精引起的不同行为变化的机制:
我们建议研究的基因都是保守的。
果蝇对人类的影响,拟议的研究将增进我们对果蝇的分子理解
调节酒精引起的行为变化的机制反过来将导致新的识别。
治疗酒精滥用障碍的危险因素和治疗目标。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Adrian Rothenfluh其他文献
Adrian Rothenfluh的其他文献
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{{ truncateString('Adrian Rothenfluh', 18)}}的其他基金
Transcriptional Regulation of Alcohol Sensitivity and Tolerance
酒精敏感性和耐受性的转录调控
- 批准号:
10651398 - 财政年份:2023
- 资助金额:
$ 34.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10889349 - 财政年份:2021
- 资助金额:
$ 34.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10471924 - 财政年份:2021
- 资助金额:
$ 34.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10683122 - 财政年份:2021
- 资助金额:
$ 34.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10738062 - 财政年份:2021
- 资助金额:
$ 34.31万 - 项目类别:
Control of Alcohol Responses by Actin-Regulating Genes
肌动蛋白调节基因控制酒精反应
- 批准号:
10306135 - 财政年份:2021
- 资助金额:
$ 34.31万 - 项目类别:
ATAC-ing dopaminergic cell identity with single-cell resolution
ATAC-ing 多巴胺能细胞识别与单细胞分辨率
- 批准号:
9980840 - 财政年份:2019
- 资助金额:
$ 34.31万 - 项目类别:
Mechanisms of alcohol-induced plasticitey mediated by Arf6
Arf6介导的酒精诱导可塑性机制
- 批准号:
10165421 - 财政年份:2018
- 资助金额:
$ 34.31万 - 项目类别:
Mechanisms of alcohol-induced plasticitey mediated by Arf6
Arf6介导的酒精诱导可塑性机制
- 批准号:
10414927 - 财政年份:2018
- 资助金额:
$ 34.31万 - 项目类别:
Engineering Drosophila that self-administer cocaine
工程果蝇自我管理可卡因
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9439365 - 财政年份:2017
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$ 34.31万 - 项目类别:
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