Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation.

Ellen I Hartig,Benjamin L King,James A Coffman,Shusen Zhu

doi:10.1242/bio.020065

Ellen I Hartig, Benjamin L King + Show 2 more

Open Access

https://doi.org/10.1242/bio.020065

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Journal: Biology open	Publication Date: Jul 21, 2016
Citations: 56	License type: CC BY 3.0

Affiliation: Mount Desert Island Biological Laboratory

Abstract

ABSTRACTChronic early-life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with cortisol and examined the effects on both larvae and adults. Treated larvae had elevated whole-body cortisol and glucocorticoid signaling, and upregulated genes associated with defense response and immune system processes. In adulthood the treated fish maintained elevated basal cortisol levels in the absence of exogenous cortisol, and constitutively mis-expressed genes involved in defense response and its regulation. Adults derived from cortisol-treated embryos displayed defective tailfin regeneration, heightened basal expression of pro-inflammatory genes, and failure to appropriately regulate those genes following injury or immunological challenge. These results support the hypothesis that chronically elevated glucocorticoid signaling early in life directs development of a pro-inflammatory adult phenotype, at the expense of immunoregulation and somatic regenerative capacity.

Highlights

Chronic psychosocial stress contributes significantly to a wide variety of public health problems endemic to the modern world, many of which are linked to chronic inflammation (Berk et al, 2013; Christian et al, 2006; Cohen et al, 2007; Pawelec et al, 2014; Radek, 2010)
Glucocorticoid signaling is activated in zebrafish embryos exposed to exogenous cortisol Zebrafish embryos treated continuously with sub- to low-micromolar doses of exogenous cortisol from 0 to 5 days post-fertilization were found to produce morphologically normal larvae (Fig. 1A), but with elevated whole body cortisol levels, as indicated by ELISA of larval extracts (Fig. 1B)
Treated larvae had an elevated heart rate and increased levels of reactive oxygen species (Fig. S2), expected effects of stress signaling. We conclude from these results that zebrafish embryos treated with exogenous cortisol activate glucocorticoid receptor signaling and mount a systemic stress-response

Summary

Introduction

Chronic psychosocial stress contributes significantly to a wide variety of public health problems endemic to the modern world, many of which are linked to chronic inflammation (Berk et al, 2013; Christian et al, 2006; Cohen et al, 2007; Pawelec et al, 2014; Radek, 2010). Adult fish derived from the treated embryos were found on average to have constitutively elevated basal cortisol levels (Fig. 2A), indicating that the treatment had a long-term activating effect on the stress system.

Results

Conclusion