Feeding entrainment of the primary and accessory loops of the molecular circadian clock and epigenetic processes in zebrafish brain: the importance of the glucocorticoid signalling

The molecular circadian clock is synchronized by environmental stimuli, allowing fish to predict external cyclic changes. Different molecular pathways are synchronized by the clock system, which is in turn affected by their output, as proved for the glucocorticoids (GCs) activity. We used a GC receptor ( gr ) KO (null mutant) zebrafish line ( gr −/−) to investigate the importance of GCs on the molecular clock, and the involvement in metabolic and epigenetic processes. Moreover, we investigated the relevance of feeding time on these processes using different time schedules (mid-light feeding, ML; mid-dark feeding, MD). Our analysis revealed that the clock genes analyzed in zebrafish brain responded differently, since genes of the primary loop ( bmal1a , per1b ) conserved the rhythm in all conditions, while genes of the secondary loop ( rev-erbα , rorα ) were affected by the genotype or the feeding time. bdnf, a neurotrophin regulated by the circadian system and known to interact with GCs, was more affected by the feeding time, whereas pparα , which links the clock system to metabolism, was affected not only by the feeding time but also by the lack of Gr. Additionally, epigenetic genes were more influenced by the loss of Gr during the day when comparing the genotypes by plotting day and night data separately. Our data suggest that GCs and feeding time can interact and influence each other modulating the molecular clock system in zebrafish brain.