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

K.A. Demin*, A.M. Lakstygal, N.A. Krotova, A. Masharsky, N. Tagawa, M.V. Chernysh, N.P. Ilyin, A.S. Taranov, D.S. Galstyan, K.A. Derzhavina, N.A. Levchenko, T.O. Kolesnikova, M.S. Mor, M.L. Vasyutina, E.V. Efimova, N. Katolikova, A.D. Prjibelski, R.R. Gainetdinov, M.S. de Abreu, T.G. AmstislavskayaT. Strekalova, A.V. Kalueff*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Web of Science)

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.
Original languageEnglish
Article number19981
Number of pages20
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 17 Nov 2020

Keywords

  • animal-models
  • anxiety-like behavior
  • chronic mild stress
  • depression-like behavior
  • gene set enrichment
  • inflammatory markers
  • monoamine levels
  • neuroscience research
  • neurotransmitter systems
  • pituitary-adrenal axis
  • GENE SET ENRICHMENT
  • CHRONIC MILD STRESS
  • ANXIETY-LIKE BEHAVIOR
  • INFLAMMATORY MARKERS
  • NEUROTRANSMITTER SYSTEMS
  • DEPRESSION-LIKE BEHAVIOR
  • ANIMAL-MODELS
  • NEUROSCIENCE RESEARCH
  • MONOAMINE LEVELS
  • PITUITARY-ADRENAL AXIS

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