The role of the Glucocorticoid Receptor in the Regulation of Diel Rhythmicity

Gayathri Jaikumar,Hans Slabbekoorn,Jenni Sireeni,Marcel Schaaf,Christian Tudorache

doi:10.1016/j.physbeh.2020.112991

Gayathri Jaikumar, Hans Slabbekoorn + Show 3 more

Open Access

https://doi.org/10.1016/j.physbeh.2020.112991

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Journal: Physiology & Behavior	Publication Date: Jun 1, 2020
Citations: 13	License type: cc-by

Affiliation: Leiden University

Abstract

Virtually all organisms have adapted to the earth's day-night cycles by the evolution of endogenous rhythms that regulate most biological processes. Recent research has highlighted the role of glucocorticoids and the Glucocorticoid receptor (GR) in coordinating clock function across various levels of biological organisation. In the present study, we have explored the role of the GR in the rhythmicity of the biological clock, by comparing 5 day old wildtype zebrafish larvae (gr+) with mutant larvae with a non-functional GR (grs357). The mutants display a weaker rhythmicity in locomotor activity in wildtypes than in mutants, while the rhythmicity of the angular velocity was higher for wildtypes. The melatonin production of the mutants showed a weaker rhythmicity, but surprisingly, there were no differences in the rhythmicity of clock-related gene expression between genotypes that could explain a mechanism for GR functionality at the transcriptional level. Furthermore, our results show that grs357 larvae have a more erratic swimming path, and cover more distance during locomotor activity than wild type larvae, in line with previously described behaviour of this mutant. Therefore, these results suggest that GR affects the diel rhythmicity of zebrafish larvae at the behavioural and endocrine level, but that these effects are not mediated by changes in the expression of clock-related genes.

Highlights

All organisms are exposed to day-night cycles as a consequence of the earth's planetary rotations around the sun [33]
Locomotor activity was determined by tracking individual fish over time and analysing the quantity of locomotor activity, path, and relative time spent in the outer zone, using automated tracking software
Using a similar type of analysis we compared the areas under the curve (AUC, dimensionless) to each other, as a measurement for net activity of the two genotypes, and a t-test revealed a lower net activity in the wild type than in the Gr-deficient strain (t-test, p = 0.0012, N=36; Fig. 2c)

Summary

Introduction

All organisms are exposed to day-night cycles as a consequence of the earth's planetary rotations around the sun [33]. The ability to anticipate and adapt to such diel changes in the environment imparts an evolutionary advantage to most species [26] In vertebrates, this has resulted in the development of a complex network of autonomously functioning central and peripheral clocks interacting through molecular and hormonal signalling to coordinate and regulate endogenous circadian (circa 24h in the absence of external cues) rhythms [44]. A heterodimer of two members of the bHLH-PAS family of proteins, namely CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle ARNT-like protein 1) activates the transcription of the period (PER1, PER2 and PER3) and cryptochrome (CRY1, CRY2) genes upon binding to specific E-box regulatory sequences in the promoter regions of these genes This leads to the increased production of the PER and CRY proteins, and their subsequent nuclear localisation, which takes several hours and peaks at the end of diel day time. Recent research efforts have focussed on identifying the additional regulatory factors involved in the coordination of clock rhythmicity across various levels of biological functioning

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