Long lasting anxiety following early life stress is dependent on glucocorticoid signaling in zebrafish. Academic Article uri icon


  • 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.

published proceedings

  • Sci Rep

altmetric score

  • 21.15

author list (cited authors)

  • Chin, J., Phan, T., Albert, L. T., Keene, A. C., & Dubou, E. R.

citation count

  • 4

complete list of authors

  • Chin, Jacqueline SR||Phan, Tram-Anh N||Albert, Lydia T||Keene, Alex C||DubouĂ©, Erik R

publication date

  • July 2022