PUBLICATION

Prolonged 5-week and 12-week chronic stress differentially modulates CNS expression of pro- and anti-neuroinflammatory biomarkers, brain monoamines and affective behavior in adult zebrafish

Authors
Kotova, M.M., Amikishiev, S.V., Apukhtin, K.V., Galstyan, D.S., de Abreu, M.S., Stewart, A.M., Yang, L., Kalueff, A.V.
ID
ZDB-PUB-250413-3
Date
2025
Source
Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology : (Journal)
Registered Authors
Keywords
Anxiety, Chronic unpredictable stress, Depression, Neuroinflammation, Zebrafish
MeSH Terms
  • Animals
  • Behavior, Animal
  • Biogenic Monoamines*/metabolism
  • Biomarkers/metabolism
  • Brain*/metabolism
  • Hydrocortisone/metabolism
  • Male
  • Microglia/metabolism
  • Stress, Psychological*/metabolism
  • Zebrafish*/metabolism
  • Zebrafish*/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
40220038 Full text @ J. Comp. Physiol. B
Abstract
Chronic stress is a major cause of affective pathogenesis, such as anxiety and depression. Experimental animal models, including rodents and zebrafish, are a valuable tool for translational neuroscience research focusing on stress-related brain disorders. Here, we examined the effects of 5- and 12-week chronic unpredictable stress (CUS5 and CUS12) on zebrafish behavior, whole-body cortisol and neuroinflammation-related biomarker gene expression, including markers of pro-inflammatory microglia (NOS2a, COX2, P75NTR) and astroglia (C3, GBP), and markers of anti-inflammatory microglia (ARG-1, CD206) and astroglia (S100a10, PTX). We also assessed stress-induced changes in brain monoamine levels and brain-blood-barrier permeability. Overall, CUS5 induced anxiety-like behavior, accompanied by elevated CNS pro-inflammatory marker gene expression, cortisol signaling and norepinephrine levels. In contrast, CUS12 induced depression-like behavior, accompanied by lowered cortisol levels, impaired serotonin turnover and activated anti-inflammatory biomarker gene expression, as well as upregulated histone deacetylase 4 gene (suggesting the involvement of epigenetic regulation). Collectively, this confirms the importance of stress duration as a key factor in the development of stress-related disorders in zebrafish models, and further implicates pro- and inti-inflammatory neuroglia in affective pathogenesis.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping