PUBLICATION

Profound effects of glucocorticoid resistance on anxiety-related behavior in zebrafish adults but not in larvae

Authors
Sireeni, J., Bakker, N., Jaikumar, G., Obdam, D., Slabbekoorn, H., Tudorache, C., Schaaf, M.
ID
ZDB-PUB-200403-131
Date
2020
Source
General and comparative endocrinology   292: 113461 (Journal)
Registered Authors
Schaaf, Marcel J. M.
Keywords
Anxiety, Behavior, Depression, Glucocorticoid receptor, Glucocorticoids, Zebrafish
MeSH Terms
  • Animals
  • Anxiety/pathology*
  • Behavior, Animal/drug effects*
  • Darkness
  • Glucocorticoids/pharmacology*
  • Larva/drug effects
  • Zebrafish/physiology*
PubMed
32194047 Full text @ Gen. Comp. Endocrinol.
Abstract
Previously, adult zebrafish with a mutation in the gene encoding the glucocorticoid receptor (Gr) were demonstrated to display anxiety- and depression-like behavior that could be reversed by treatment with antidepressant drugs, suggesting that this model system could be applied to study novel therapeutic strategies against depression. Subsequent studies with zebrafish larvae from this grs357 line and a different gr mutant have not confirmed these effects. To investigate this discrepancy, we have analyzed the anxiety-like behavior in 5 dpf grs357 larvae using a dark/tapping stimulus test and a light/dark preference test. In addition, grs357 adult fish were subjected to an open field test. The results showed that in larvae the mutation mainly affected general locomotor activity (decreased velocity in the dark/tapping stimulus test, increased velocity in the light/dark preference test). However, parameters considered specific readouts for anxiety-like behavior (response to dark/tapping stimulus, time spent in dark zone) were not altered by the mutation. In adults, the mutants displayed a profound increase in anxiety-like behavior (time spent in outer zone in open field test), besides changes in locomotor activity (decreased velocity, increased angular velocity and freezing time). We conclude that the neuronal circuitry involved in anxiety- and depression-like behavior is largely affected by deficient Gr signaling in adult fish but not in larvae, indicating that this circuitry only fully develops after the larval stages in zebrafish. This makes the zebrafish an interesting model to study the ontology of anxiety- and depression-related pathology which results from deficient glucocorticoid signaling.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping