Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment.
Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment.
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DOI：
10.1186/1471-2164-14-348
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发表时间：
2013-05-24
期刊：
影响因子：
4.4
通讯作者：
Godwin J
中科院分区：
文献类型：
--
作者：
Wong RY;Oxendine SE;Godwin J
许多生物体中都存在与压力和焦虑相关的行为。研究表明，在人类和其他动物中，使用选择性血清素再摄取抑制剂（例如氟西汀）治疗可以减少焦虑和焦虑相关行为。然而，功效和副作用因人而异。氟西汀可以以立体特异性方式调节焦虑，或者无论立体异构体如何，都具有相同的功效，具体取决于作用机制（例如血清素或 GABA 作用）。斑马鱼是一种新兴且有价值的转化模型，可用于理解焦虑等人类健康相关问题。在这项研究中，我们提供的数据显示了氟西汀治疗野生斑马鱼的行为和全脑转录组变化，并提出了这种广泛使用的药物的其他分子机制。我们使用自动行为分析来评估外消旋和立体异构氟西汀对雄性野生斑马鱼的影响。与对照组相比，氟西汀的外消旋异构体和单独异构体均减少了焦虑相关行为，并且我们没有观察到氟西汀的立体特异性效应。通过对全脑进行 RNA 测序，我们发现了 411 个基因在外消旋氟西汀治疗中表现出差异表达。当氟西汀治疗减少焦虑相关行为时，几种神经肽（神经肽 Y、异产素、尿皮质素 3、催乳素）表现出与缓解压力和焦虑一致的表达模式。通过基因本体论和 KEGG 通路分析，我们发现脂质和氨基酸代谢过程以及类固醇生物合成等术语被过度丰富。我们的结果表明，氟西汀减少了野生斑马鱼的焦虑相关行为，并改变了它们的神经基因组状态。我们确定了两个生物过程，脂质和氨基酸代谢合成，它们表征了氟西汀处理的鱼的差异。氟西汀可能作用于几种不同的分子途径，以减少野生斑马鱼的焦虑相关行为。这项研究提供的数据可以帮助确定氟西汀在动物分类群中作用的常见分子机制。
Stress and anxiety-related behaviors are seen in many organisms. Studies have shown that in humans and other animals, treatment with selective serotonin reuptake inhibitors (e.g. fluoxetine) can reduce anxiety and anxiety-related behaviors. The efficacies and side effects, however, can vary between individuals. Fluoxetine can modulate anxiety in a stereospecific manner or with equal efficacy regardless of stereoisomer depending on the mechanism of action (e.g. serotonergic or GABAergic effects). Zebrafish are an emerging and valuable translational model for understanding human health related issues such as anxiety. In this study we present data showing the behavioral and whole brain transcriptome changes with fluoxetine treatment in wild-derived zebrafish and suggest additional molecular mechanisms of this widely-prescribed drug. We used automated behavioral analyses to assess the effects of racemic and stereoisomeric fluoxetine on male wild-derived zebrafish. Both racemic and the individual isomers of fluoxetine reduced anxiety-related behaviors relative to controls and we did not observe stereospecific fluoxetine effects. Using RNA-sequencing of the whole brain, we identified 411 genes showing differential expression with racemic fluoxetine treatment. Several neuropeptides (neuropeptide Y, isotocin, urocortin 3, prolactin) showed consistent expression patterns with the alleviation of stress and anxiety when anxiety-related behavior was reduced with fluoxetine treatment. With gene ontology and KEGG pathway analyses, we identified lipid and amino acid metabolic processes, and steroid biosynthesis among other terms to be over-enriched. Our results demonstrate that fluoxetine reduces anxiety-related behaviors in wild-derived zebrafish and alters their neurogenomic state. We identify two biological processes, lipid and amino acid metabolic synthesis that characterize differences in the fluoxetine treated fish. Fluoxetine may be acting on several different molecular pathways to reduce anxiety-related behaviors in wild-derived zebrafish. This study provides data that could help identify common molecular mechanisms of fluoxetine action across animal taxa.
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影响因子：
2.7
作者：
Egan, Rupert J.;Bergner, Carisa L.;Hart, Peter C.;Cachat, Jonathan M.;Canavello, Peter R.;Elegante, Marco F.;Elkhayat, Salem I.;Bartels, Brett K.;Tien, Anna K.;Tien, David H.;Mohnot, Sopan;Beeson, Esther;Glasgow, Eric;Amri, Hakima;Zukowska, Zofia;Kalueff, Allan V.
通讯作者：
Kalueff, Allan V.
影响因子：
5.3
作者：
Deussing, Jan M.;Breu, Johannes;Wurst, Wolfgang
通讯作者：
Wurst, Wolfgang
影响因子：
3.4
作者：
Bitran, D;Foley, M;Frye, CA
通讯作者：
Frye, CA
影响因子：
4.4
作者：
Catalán A;Hutter S;Parsch J
通讯作者：
Parsch J
影响因子：
2.7
作者：
Akwa, Y;Purdy, RH;Britton, KT
通讯作者：
Britton, KT