Long lasting anxiety following early life stress is dependent on glucocorticoid signaling in zebrafish
Institutional Repository Document
Overview
Research
Identity
Other
View All
Overview
abstract
SummaryChronic 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 remains 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, 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.
