Project 3 - Molecular mechanisms of acute ethanol behaviors in C. elegans

项目 3 - 线虫急性乙醇行为的分子机制

基本信息

  • 批准号:
    10633319
  • 负责人:
  • 金额:
    $ 18.4万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-08-05 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary – Project 3 The development of alcohol use disorder (AUD) results from an interaction between both environmental and genetic factors. Studies of the impact of environment on the risk to develop AUD have, to date, focused mainly on psychological characteristics (externalizing phenotypes, etc.) or on developmental defects associated with prenatal or adolescent exposure to alcohol. Here, we will study the role of the dietary omega-3 fatty acid eicosapentaenoic acid (EPA), an environmental factor, in adults for a role in modulating the acute behavioral response to ethanol. Our study of the alcohol-naive acute level of response (LR) is significant because this measure is strongly correlated with the liability to develop AUD. Using two model organisms (C. elegans and mouse), we have previously found that dietary omega-3 fatty acid levels significantly impact the acute LR to alcohol in ethanol-naive animals. In worms, we have found specifically that EPA is essential for the development of acute functional tolerance (AFT) to ethanol. We will use two complementary approaches to identify the mechanisms underlying the effects of EPA on the acute behavioral response to ethanol. In Aim 1 we will identify genes whose expression is regulated in response to different EPA levels (depleted, normal levels, above normal levels) in adult C. elegans. We will correlate gene expression changes and the time course of the effect of dietary EPA on AFT. We will directly test the roles of prioritized candidate genes in the development of AFT to identify the molecular pathways that are important for ethanol response behaviors and are affected by EPA levels. In Aim 2, we will use cutting edge lipidomics to determine what lipid species are derived from the dietary EPA. We will correlate the accumulation of EPA derived lipids to the time course of the effects of dietary EPA on AFT. We will identify candidate lipid mediators of the development of AFT. This will implicate molecular pathways in the machinery underlying AFT. These studies will provide novel insight into the roles of lipids in regulating the level of response to alcohol. Determination of the nature of these roles will enable future identification of the protein targets of ethanol, and the regulatory mechanisms affecting those proteins, that are impacted by these lipid-dependent functions. Finally, in Aim 3, we will continue a successful approach that uses the high-throughput genetic power of C. elegans to test the hypothesized roles of genes that have been implicated by other components of the VCU-ARC in behavioral responses to ethanol.
项目摘要-项目3

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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JILL C BETTINGER其他文献

JILL C BETTINGER的其他文献

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{{ truncateString('JILL C BETTINGER', 18)}}的其他基金

Neuropeptide receptors, behavioral states and acute ethanol effects
神经肽受体、行为状态和急性乙醇效应
  • 批准号:
    10385729
  • 财政年份:
    2020
  • 资助金额:
    $ 18.4万
  • 项目类别:
Neuropeptide receptors, behavioral states and acute ethanol effects
神经肽受体、行为状态和急性乙醇效应
  • 批准号:
    10615671
  • 财政年份:
    2020
  • 资助金额:
    $ 18.4万
  • 项目类别:
Identification of natural variants that influence responses to ethanol in C. elegans
鉴定影响秀丽隐杆线虫对乙醇反应的自然变异
  • 批准号:
    10457002
  • 财政年份:
    2018
  • 资助金额:
    $ 18.4万
  • 项目类别:
Identification of natural variants that influence responses to ethanol in C. elegans
鉴定影响秀丽隐杆线虫对乙醇反应的自然变异
  • 批准号:
    10226170
  • 财政年份:
    2018
  • 资助金额:
    $ 18.4万
  • 项目类别:
Identification of natural variants that influence responses to ethanol in C. elegans
鉴定影响秀丽隐杆线虫对乙醇反应的自然变异
  • 批准号:
    9976403
  • 财政年份:
    2018
  • 资助金额:
    $ 18.4万
  • 项目类别:
Identification of natural variants that influence responses to ethanol in C. elegans
鉴定影响秀丽隐杆线虫对乙醇反应的自然变异
  • 批准号:
    9753112
  • 财政年份:
    2018
  • 资助金额:
    $ 18.4万
  • 项目类别:
Regulation of responses to alcohol by the SWI/SNF chromatin remodeling complex
SWI/SNF 染色质重塑复合物对酒精反应的调节
  • 批准号:
    9176919
  • 财政年份:
    2016
  • 资助金额:
    $ 18.4万
  • 项目类别:
Project 3 - Molecular mechanisms of acute ethanol behaviors in C. elegans
项目 3 - 线虫急性乙醇行为的分子机制
  • 批准号:
    10429953
  • 财政年份:
    2014
  • 资助金额:
    $ 18.4万
  • 项目类别:
The Genetics of Acute Tolerance to Ethanol
乙醇急性耐受的遗传学
  • 批准号:
    8051538
  • 财政年份:
    2008
  • 资助金额:
    $ 18.4万
  • 项目类别:
The Genetics of Acute Tolerance to Ethanol
乙醇急性耐受的遗传学
  • 批准号:
    7579975
  • 财政年份:
    2008
  • 资助金额:
    $ 18.4万
  • 项目类别:

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