Abstract

Exposure to stress during early development can permanently influence an individual's physiology and behaviour, and affect its subsequent health. The extent to which elevated glucocorticoids cause such long‐term ‘programming’ remains largely untested. In the present study, using the Japanese quail as our study species, we independently manipulated exposure to corticosterone during pre‐ and/or post‐natal development and investigated the subsequent effects on global gene expression profiles within the hippocampus and hypothalamus upon achieving adulthood. Our results showed that the changes in transcriptome profiles in response to corticosterone exposure clearly differed between the hippocampus and the hypothalamus. We also showed that these effects depended on the developmental timing of exposure and identified brain‐region specific gene expression patterns that were either: (i) similarly altered by corticosterone regardless of the developmental stage in which hormonal exposure occurred or (ii) specifically and uniquely altered by either pre‐natal or post‐natal exposure to corticosterone. Corticosterone‐treated birds showed alterations in networks of genes that included known markers of the programming actions of early‐life adversity (e.g. brain‐derived neurotrophic factor and mineralocorticoid receptor within the hippocampus; corticotrophin‐releasing hormone and serotonin receptors in the hypothalamus). Altogether, for the first time, these findings provide experimental support for the hypothesis that exposure to elevated glucocorticoids during development may be a key hormonal signalling pathway through which the long‐term phenotypic effects associated with early‐life adversity emerge and potentially persist throughout the lifespan. These data also highlight that stressors might have different long‐lasting impacts on the brain transcriptome depending on the developmental stage in which they are experienced; more work is now required to relate these mechanisms to organismal phenotypic differences.

Highlights

  • The responses of an organism to early-life environments can have long-term phenotypic effects, potentially persisting for the whole lifespan [1]

  • The principal component analysis (PCA) plot with only the hippocampal samples suggested a relatively good separation along PC3 across all the B-treated birds compared to the controls, suggesting an overall effect of the treatment on hippocampal gene expression

  • The findings reported in the present study indicate that Japanese quail exogenously exposed to the stress hormone corticosterone during pre- and/or post-natal stages of development showed distinct modifications in global gene expression patterns depending on the brain region and, most importantly, on the developmental stage at which the stressful treatment occurred

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Summary

Introduction

The responses of an organism to early-life environments can have long-term phenotypic effects, potentially persisting for the whole lifespan [1]. A variety of early-life adversities such as unpredictable light/dark rhythm, unpredictable access to food and intermittent social isolation, which are presumed to be associated with increased glucocorticoid levels, resulted in significant changes in the neural gene expression signature and similar directional changes were observed in the offspring [23,24,25] The effects of these types of stressors on the brain transcriptome might be driven by the direct exposure to elevated glucocorticoids during development. Using our chosen precocial study species, we aimed to test three main predictions That both pre- and post-natal exposure to corticosterone would induce similar alterations in the brain transcriptome across all the stress-exposed birds compared to the controls. Our third prediction was that certain long-term alterations in the brain transcriptome would be and uniquely dependent on either pre-natal corticosterone or postnatal corticosterone exposure

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