Feeding Entrainment of the Zebrafish Circadian Clock Is Regulated by the Glucocorticoid Receptor

Abstract

Glucocorticoids (GCs) are steroid hormones mainly acting as key regulators of body homeostasis and stress responses. Their activities are primarily based on the binding to the GC receptor (GR), a member of the nuclear receptor family, that regulates tissue-specific sets of genes. GCs secretion follows a circadian rhythmicity with a peak linked to the animal’s activity phase. In mammals, GCs are also implicated in feeding entrainment mechanisms as internal zeitgeber. Here, we investigated, by means of behavioural and molecular approaches, the circadian clock and its regulation by light and food in wild-type (WT) and null glucocorticoid receptor (gr−/−) zebrafish larvae, juveniles and adults. In both WT and gr−/− larvae and adults, behavioural activity and clock gene expression were entrained to the light–dark (LD) cycle and rhythmic in constant conditions. Differences in the pattern of clock genes’ expression indicated a modulatory role of GCs. A significant role of Gr was detected in the feeding entrainment which was absent or markedly dampened in mutants. Furthermore, the expression of two clock-regulated genes involved in glucidic and lipidic metabolism was altered, highlighting the participation of GCs in metabolic processes also in fish. Taken together, our results confirmed the role of GC-mediated Gr signaling in the feeding entrainment in a non-mammalian species, the zebrafish.

Glucocorticoid receptor activities in the zebrafish model: a review

“…While the rhythmicity of pck2 is completely abolished, srebp1 rhythm undergoes a phase shift, anticipating the acrophase of its expression. The study confirms that, like in mammals (Challet 2019), in non-mammalian vertebrates GC/Gr may function as an endocrine signal able to regulate feeding synchronization with circadian clocks (Morbiato et al 2019).…”

“…The transgenic line ia20 was similarly used to monitor GC activity in the first CRISPR/Cas9 zebrafish mutant line developed for Gr (Facchinello et al 2017, Morbiato et al 2019, to study the cross-talk between GC/Gr and the hypoxic transcriptional responses (Vettori et al 2017), to demonstrate how an increase of cortisol induced by stress impairs the regenerative potential of zebrafish heart (Sallin & Jaźwińska 2016) and to visualize the renin effects on pronephros development, as this line shows a robust expression of EGFP in fish kidney (Schaeffer et al 2019).…”

Zebrafish (Danio rerio) physiological and behavioural responses to insect-based diets: a multidisciplinary approach

“…Scientific RepoRtS | (2020) 10:10648 | https://doi.org/10.1038/s41598-020-67740-w www.nature.com/scientificreports/ Photic behavioural entrainment test. The photic behavioural entrainment test was performed following a standard procedure 63 . Because the test required extended recordings, zebrafish were tested in groups formed by four individuals to avoid social isolation.…”

“…A minimal distance moved of 2 mm was used. In case of normal photic behavioural entrainment, zebrafish were expected to show markedly diurnal activity 63 .…”

Introducing the Amphibious Mudskipper Goby as a Unique Model to Evaluate Neuro/Endocrine Regulation of Behaviors Mediated by Buccal Sensation and Corticosteroids

“…These findings suggest that GRs/MRs are critical for many physiological and behavioral responses, such as the regulation of salt intake, mood, appetite, exploratory behavior and visual responses [77,[85][86][87]. Indeed, zebrafish and medaka models with constitutive GR or MR knockout fail to integrate these brain behavior and visual responses as well as regulate the stress axis, although they can grow and osmoregulate [77,80,[88][89][90][91][92][93][94][95][96][97]. The simple aquatic preference of mudskippers may also reflect these behaviors.…”