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

Min Kyeung Choi*, Alexander Cook, Kanak Mungikar, Helen Eachus, Anna Tochwin, Matthias Linke, Susanne Gerber, Soojin Ryu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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) are 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.
Original languageEnglish
Article number110160
JournaliScience
Volume27
Issue number7
Early online date31 May 2024
DOIs
Publication statusE-pub ahead of print - 31 May 2024

Bibliographical note

Copyright © 2024 The Author(s). Published by Elsevier Inc. This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Keywords

  • Behavioral neuroscience
  • Molecular neuroscience
  • Neuroscience
  • Omics
  • Transcriptomics

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