PUBLICATION

Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish

Authors
Demin, K.A., Lakstygal, A.M., Krotova, N.A., Masharsky, A., Tagawa, N., Chernysh, M.V., Ilyin, N.P., Taranov, A.S., Galstyan, D.S., Derzhavina, K.A., Levchenko, N.A., Kolesnikova, T.O., Mor, M.S., Vasyutina, M.L., Efimova, E.V., Katolikova, N., Prjibelski, A.D., Gainetdinov, R.R., de Abreu, M.S., Amstislavskaya, T.G., Strekalova, T., Kalueff, A.V.
ID
ZDB-PUB-201120-156
Date
2020
Source
Scientific Reports   10: 19981 (Journal)
Registered Authors
Kalueff, Allan V.
Keywords
none
MeSH Terms
  • Animals
  • Antidepressive Agents/pharmacology
  • Anxiety/drug therapy
  • Anxiety/physiopathology
  • Behavior, Animal/drug effects
  • Behavior, Animal/physiology*
  • Brain/drug effects
  • Brain/physiopathology
  • Disease Models, Animal
  • Female
  • Fluoxetine/pharmacology
  • Male
  • Stress, Psychological/drug therapy
  • Stress, Psychological/physiopathology*
  • Transcriptome/drug effects
  • Transcriptome/physiology*
  • Zebrafish/physiology*
PubMed
33203921 Full text @ Sci. Rep.
Abstract
Stress-related neuropsychiatric disorders are widespread, debilitating and often treatment-resistant illnesses that represent an urgent unmet biomedical problem. Animal models of these disorders are widely used to study stress pathogenesis. A more recent and historically less utilized model organism, the zebrafish (Danio rerio), is a valuable tool in stress neuroscience research. Utilizing the 5-week chronic unpredictable stress (CUS) model, here we examined brain transcriptomic profiles and complex dynamic behavioral stress responses, as well as neurochemical alterations in adult zebrafish and their correction by chronic antidepressant, fluoxetine, treatment. Overall, CUS induced complex neurochemical and behavioral alterations in zebrafish, including stable anxiety-like behaviors and serotonin metabolism deficits. Chronic fluoxetine (0.1 mg/L for 11 days) rescued most of the observed behavioral and neurochemical responses. Finally, whole-genome brain transcriptomic analyses revealed altered expression of various CNS genes (partially rescued by chronic fluoxetine), including inflammation-, ubiquitin- and arrestin-related genes. Collectively, this supports zebrafish as a valuable translational tool to study stress-related pathogenesis, whose anxiety and serotonergic deficits parallel rodent and clinical studies, and genomic analyses implicate neuroinflammation, structural neuronal remodeling and arrestin/ubiquitin pathways in both stress pathogenesis and its potential therapy.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping