# Exposure to elevated glucocorticoid during development primes altered transcriptional responses to acute stress in adulthood

## TL;DR

Early exposure to high glucocorticoids in zebrafish leads to long-term changes in brain gene activity and stress responses in adulthood.

## Contribution

A new zebrafish model reveals molecular and epigenetic changes from early glucocorticoid exposure linked to adult stress responses.

## Key findings

- hdGC exposure primes altered gene expression in adult zebrafish brains under acute stress.
- The primed genes are enriched in human psychiatric disorder risk factors.
- Epigenetic regulatory elements show lasting changes after hdGC exposure.

## Abstract

Early life stress (ELS) is a major risk factor for developing psychiatric disorders, with glucocorticoids (GCs) implicated in mediating its effects in shaping adult phenotypes. In this process, exposure to high levels of developmental GC (hdGC) is thought to induce molecular changes that prime differential adult responses. However, identities of molecules targeted by hdGC exposure are not completely known. Here, we describe lifelong molecular consequences of hdGC exposure using a newly developed zebrafish double-hit stress model, which shows altered behaviors and stress hypersensitivity in adulthood. We identify a set of primed genes displaying altered expression only upon acute stress in hdGC-exposed adult fish brains. Interestingly, this gene set is enriched in risk factors for psychiatric disorders in humans. Lastly, we identify altered epigenetic regulatory elements following hdGC exposure. Thus, our study provides comprehensive datasets delineating potential molecular targets mediating the impact of hdGC exposure on adult responses.

•High level of developmental GC exposure (hdGC) alters adult behavior in zebrafish•hdGC primes exaggerated endocrine and transcriptional stress response in adults•We identify a set of hdGC-primed genes in the brain and their associated functions•We identify lasting impact of hdGC exposure on epigenetic modulator expressions

High level of developmental GC exposure (hdGC) alters adult behavior in zebrafish

hdGC primes exaggerated endocrine and transcriptional stress response in adults

We identify a set of hdGC-primed genes in the brain and their associated functions

We identify lasting impact of hdGC exposure on epigenetic modulator expressions

Neuroscience; Behavioral neuroscience; Molecular neuroscience; Omics; Transcriptomics