Abstract

Excess glucocorticoid transferred from stressed mother to the embryo affects developing vertebrate offspring, but the underlying programming events are unclear. In this study, we tested the hypothesis that increased zygotic glucocorticoid deposition, mimicking a maternal stress scenario, modifies early brain development and larval behaviour in zebrafish (Danio rerio). Cortisol was microinjected into the yolk at one cell-stage, to mimic maternal transfer, and the larvae [96 hours post-fertilization (hpf)] displayed increased activity in light and a reduction in thigmotaxis, a behavioural model for anxiety, suggesting an increased propensity for boldness. This cortisol-mediated behavioural phenotype corresponded with an increase in primary neurogenesis, as measured by incorporation of EdU at 24 hpf, in a region-specific manner in the preoptic region and the pallium, the teleostean homolog of the hippocampus. Also, cortisol increased the expression of the proneural gene neurod4, a marker of neurogenesis, in a region- and development-specific manner in the embryos. Altogether, excess zygotic cortisol, mimicking maternal stress, affects early brain development and behavioural phenotype in larval zebrafish. We propose a key role for cortisol in altering brain development leading to enhanced boldness, which may be beneficial in preparing the offspring to a stressful environment and enhancing fitness.

Highlights

  • Highly conserved and has been observed in larval zebrafish[20,21,22], fifth-instar larvae of migratory locusts[23], and in rodents[24,25]

  • Our results demonstrate that elevated zygotic cortisol levels, mimicking cortisol transfer from stressed mothers to offspring, enhanced boldness in larval zebrafish as measured in behavioural assays

  • This behavioural phenotype corresponded with increased neurogenesis at 24 hpf, implicating for the first time a role for excess cortisol deposition in response to maternal stress as a mediator of brain development and function in zebrafish

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Summary

Introduction

Highly conserved and has been observed in larval zebrafish[20,21,22], fifth-instar larvae of migratory locusts[23], and in rodents[24,25]. Thigmotaxis is another behavioural assay used to assess anxiety in rodents[26] and was adapted for use with zebrafish[27]. 1-cell stage embryos were microinjected with cortisol to mimic elevated maternal deposition, and the resulting effect on neurogenesis and larval behaviour were assessed

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