PUBLICATION

Long lasting anxiety following early life stress is dependent on glucocorticoid signaling in zebrafish

Authors
Chin, J.S.R., Phan, T.N., Albert, L.T., Keene, A.C., Duboué, E.R.
ID
ZDB-PUB-220729-1
Date
2022
Source
Scientific Reports   12: 12826 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Adverse Childhood Experiences*
  • Animals
  • Anxiety
  • Glucocorticoids
  • Hydrocortisone
  • Receptors, Glucocorticoid/genetics
  • Receptors, Glucocorticoid/metabolism
  • Stress, Psychological
  • Zebrafish*/metabolism
PubMed
35896563 Full text @ Sci. Rep.
Abstract
Chronic adversity in early childhood is associated with increased anxiety and a propensity for substance abuse later in adulthood, yet the effects of early life stress (ELS) on brain development remain poorly understood. The zebrafish, Danio rerio, is a powerful model for studying neurodevelopment and stress. Here, we describe a zebrafish model of ELS and identify a role for glucocorticoid signaling during a critical window in development that leads to long-term changes in brain function. Larval fish subjected to chronic stress in early development exhibited increased anxiety-like behavior and elevated glucocorticoid levels later in life. Increased stress-like behavior was only observed when fish were subjected to ELS within a precise time window in early development, revealing a temporal critical window of sensitivity. Moreover, enhanced anxiety-like behavior only emerges after two months post-ELS, revealing a developmentally specified delay in the effects of ELS. ELS leads to increased levels of baseline cortisol, and resulted in a dysregulation of cortisol receptors' mRNA expression, suggesting long-term effects on cortisol signaling. Together, these findings reveal a 'critical window' for ELS to affect developmental reprogramming of the glucocorticoid receptor pathway, resulting in chronic elevated stress.
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Human Disease / Model
Sequence Targeting Reagents
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