Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment

Ryan Wong, Sarah E. Oxendine, John Godwin

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Background: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Article number348
JournalBMC genomics
Volume14
Issue number1
DOIs
StatePublished - May 24 2013

Fingerprint

Fluoxetine
Zebrafish
Transcriptome
Anxiety
GABA Agents
Urocortins
RNA Sequence Analysis
Biological Phenomena
Lipids
Amino Acids
Gene Ontology
Stereoisomerism
Neuropeptide Y
Serotonin Uptake Inhibitors
Brain
Neuropeptides
Prolactin
Fishes
Steroids

Keywords

  • Anxiety
  • Brain
  • Fluoxetine
  • GABA
  • Genomic
  • RNA-sequencing
  • SSRI
  • Serotonin
  • Stress
  • Zebrafish

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment. / Wong, Ryan; Oxendine, Sarah E.; Godwin, John.

In: BMC genomics, Vol. 14, No. 1, 348, 24.05.2013.

Research output: Contribution to journalArticle

@article{29eec9631cad46f9b5ece549987cd1f6,
title = "Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment",
abstract = "Background: 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. Results: 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. Conclusion: 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.",
keywords = "Anxiety, Brain, Fluoxetine, GABA, Genomic, RNA-sequencing, SSRI, Serotonin, Stress, Zebrafish",
author = "Ryan Wong and Oxendine, {Sarah E.} and John Godwin",
year = "2013",
month = "5",
day = "24",
doi = "10.1186/1471-2164-14-348",
language = "English (US)",
volume = "14",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment

AU - Wong, Ryan

AU - Oxendine, Sarah E.

AU - Godwin, John

PY - 2013/5/24

Y1 - 2013/5/24

N2 - Background: 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. Results: 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. Conclusion: 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.

AB - Background: 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. Results: 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. Conclusion: 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.

KW - Anxiety

KW - Brain

KW - Fluoxetine

KW - GABA

KW - Genomic

KW - RNA-sequencing

KW - SSRI

KW - Serotonin

KW - Stress

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=84878009771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878009771&partnerID=8YFLogxK

U2 - 10.1186/1471-2164-14-348

DO - 10.1186/1471-2164-14-348

M3 - Article

VL - 14

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 348

ER -