The omega-3 fatty acid eicosapentaenoic acid is required for normal alcohol response behaviors in C. elegans.
The omega-3 fatty acid eicosapentaenoic acid is required for normal alcohol response behaviors in C. elegans.
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DOI：
10.1371/journal.pone.0105999
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bettinger JC
中科院分区：
文献类型：
--
作者：
Raabe RC;Mathies LD;Davies AG;Bettinger JC
酒精成瘾是一个普遍的社会问题，对此几乎没有治疗方法。滥用倾向有显着的遗传和环境影响，了解这些因素将是重要的易感个体的识别和有效的药物治疗的发展。在人类中，对酒精的反应水平强烈预测随后的酒精滥用。反应水平是对酒精的抵消反应，对药物的敏感性水平和药物暴露期间耐受性发展的程度的组合，称为急性功能性耐受性。我们使用简单的和良好的特征化的神经系统秀丽隐杆线虫模型的急性行为效应的乙醇，以确定遗传和环境因素，影响水平的响应乙醇。鉴于蠕虫和人类的神经生物学机制之间的强分子保守性，乙醇的细胞水平效应可能是保守的。长链多不饱和脂肪酸水平的变化越来越多地与人类复杂的神经生物学表型有关，我们最近发现脂肪酸水平改变了蠕虫的乙醇反应。在这里，我们报告1）二十碳五烯酸，一种ω-3多不饱和脂肪酸，是急性功能耐受性发展所必需的，2）饮食补充二十碳五烯酸足以实现急性耐受性，3）饮食二十碳五烯酸可以改变野生型对乙醇的反应。这些结果表明，影响长链多不饱和脂肪酸水平的遗传变异可能是重要的滥用倾向位点，饮食中的多不饱和脂肪酸可能是一个重要的环境调节剂的行为反应乙醇。
Alcohol addiction is a widespread societal problem, for which there are few treatments. There are significant genetic and environmental influences on abuse liability, and understanding these factors will be important for the identification of susceptible individuals and the development of effective pharmacotherapies. In humans, the level of response to alcohol is strongly predictive of subsequent alcohol abuse. Level of response is a combination of counteracting responses to alcohol, the level of sensitivity to the drug and the degree to which tolerance develops during the drug exposure, called acute functional tolerance. We use the simple and well-characterized nervous system of Caenorhabditis elegans to model the acute behavioral effects of ethanol to identify genetic and environmental factors that influence level of response to ethanol. Given the strong molecular conservation between the neurobiological machinery of worms and humans, cellular-level effects of ethanol are likely to be conserved. Increasingly, variation in long-chain polyunsaturated fatty acid levels has been implicated in complex neurobiological phenotypes in humans, and we recently found that fatty acid levels modify ethanol responses in worms. Here, we report that 1) eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, is required for the development of acute functional tolerance, 2) dietary supplementation of eicosapentaenoic acid is sufficient for acute tolerance, and 3) dietary eicosapentaenoic acid can alter the wild-type response to ethanol. These results suggest that genetic variation influencing long-chain polyunsaturated fatty acid levels may be important abuse liability loci, and that dietary polyunsaturated fatty acids may be an important environmental modulator of the behavioral response to ethanol.
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DOI：
10.1111/j.1530-0277.2011.01699.x
发表时间：
2012-06-01
影响因子：
3.2
作者：
Kalu, Nnenna;Ramchandani, Vijay A.;Taylor, Robert
通讯作者：
Taylor, Robert
影响因子：
3.9
作者：
Kulas, Jana;Schmidt, Cosima;Menzel, Ralph
通讯作者：
Menzel, Ralph
影响因子：
5.2
作者：
Barbadoro, Pamela;Annino, Isidoro;Minelli, Andrea
通讯作者：
Minelli, Andrea
影响因子：
2.5
作者：
Kapfhamer, D.;Bettinger, J. C.;McIntire, S. L.
通讯作者：
McIntire, S. L.
DOI：
10.1126/science.1235753
发表时间：
2013-08-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ma DK;Rothe M;Zheng S;Bhatla N;Pender CL;Menzel R;Horvitz HR
通讯作者：
Horvitz HR