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三个斑马鱼(Danio rerio)种群中酒精作用的行为遗传学

Behavioral genetics of alcohol's effects in three zebrafish (Danio rerio) populations.

作者信息

Agues-Barbosa Thais, da Silva Junior Francisco Carlos, Gomes-de-Lima Jackson Nazareno, Batistuzzo de Medeiros Silvia Regina, Luchiari Ana Carolina

机构信息

Department of Physiology & Behavior, Universidade Federal do Rio Grande do Norte, Rio Grande do Norte, Brazil.

Department of Molecular Biology and Genetics, Universidade Federal do Rio Grande do Norte, Rio Grande do Norte, Brazil.

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Mar 2;114:110495. doi: 10.1016/j.pnpbp.2021.110495. Epub 2021 Dec 14.

Abstract

Alcohol abuse is one of the most dangerous and serious problems for patients and society. Interpopulation studies are important in understanding how genetic background contributes to the effects of alcohol. In this study, we applied a chronic alcohol exposure protocol in three zebrafish populations (Danio rerio; both sexes; AB, TU, and outbred fish - OB). We analyzed the behavioral responses and mRNA expression involved in neurotransmitter metabolism - th1, tph1, ache, ada1, gaba1, gad1b, and bdnf. Locomotion patterns were similar between populations (increased speed after acute alcohol and unaltered locomotion after chronic and withdrawal treatments). All populations exhibited increased expression of genes associated with locomotion (th1, gad1b, and gaba1) after acute alcohol exposure. Anxiety-like responses increased in AB and TU fish during withdrawal and decreased in AB fish after acute alcohol exposure. Genes related to anxiety-like behavior (tph1 and ada1) were overexpressed in AB and TU fish after acute and withdrawal treatments, while OB fish exhibited unaltered responses. Bdnf levels decreased during withdrawal in AB and OB fish, while TU showed upregulated levels in both chronic and withdrawal treatments. Our results suggest that zebrafish populations respond differently to alcohol exposure, which may contribute to understanding the mechanisms underlying alcohol use and dependence. Moreover, we found that a more diverse genetic background (OB) was related to higher variability in behavioral and mRNA expression, demonstrating that inbred populations (AB and TU) may be useful tools in identifying alcohol use and abuse mechanisms.

摘要

酒精滥用对患者和社会来说是最危险、最严重的问题之一。群体间研究对于理解基因背景如何影响酒精作用非常重要。在本研究中,我们对三个斑马鱼群体(斑马鱼;雌雄均有;AB、TU和远交系鱼类——OB)应用了慢性酒精暴露方案。我们分析了神经递质代谢相关的行为反应和mRNA表达——th1、tph1、ache、ada1、gaba1、gad1b和bdnf。各群体间的运动模式相似(急性酒精处理后速度增加,慢性和戒断处理后运动无变化)。所有群体在急性酒精暴露后与运动相关的基因(th1、gad1b和gaba1)表达均增加。AB和TU鱼类在戒断期间类似焦虑的反应增加,AB鱼类在急性酒精暴露后类似焦虑的反应减少。在急性和戒断处理后,AB和TU鱼类中与类似焦虑行为相关的基因(tph1和ada1)过度表达,而OB鱼类表现出无变化的反应。AB和OB鱼类在戒断期间bdnf水平下降,而TU在慢性和戒断处理中均表现出bdnf水平上调。我们的结果表明,不同斑马鱼群体对酒精暴露的反应不同,这可能有助于理解酒精使用和依赖的潜在机制。此外,我们发现遗传背景更多样化的群体(OB)与行为和mRNA表达的更高变异性相关,这表明近交群体(AB和TU)可能是识别酒精使用和滥用机制的有用工具。

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