Long lasting anxiety following early life stress is dependent on glucocorticoid signaling in zebrafish
| Autor: | Alex C. Keene, Jacqueline S. R. Chin, Lydia T. Albert, Erik R. Duboué, Phan Tn |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Multidisciplinary Hydrocortisone Danio Anxiety Biology biology.organism_classification Receptors Glucocorticoid Endocrinology Glucocorticoid receptor Adverse Childhood Experiences Internal medicine medicine Animals Chronic stress medicine.symptom Receptor Glucocorticoids Reprogramming Zebrafish Stress Psychological Glucocorticoid medicine.drug |
| DOI: | 10.1101/2021.05.25.445598 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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