Administration time-dependent effects of poly (I:C) on antioxidant and immune responses along the diurnal time scale in zebrafish

Abstract

The circadian clock of vertebrates regulates many biological processes, including the immune system. This paper investigated whether responsiveness to poly (I:C), a synthetic analog of double-stranded RNA used as an immunostimulant, exhibits day/night differences in zebrafish. Fish were intraperitoneally (IP) injected with either phosphate-buffered saline (PBS) or poly (I:C) at two different time points: "Zeitgeber Time" (ZT) 4 (day) and ZT16 (night). Then, 6 h later, fish were euthanized, and tissue samples (skin, liver and kidney) were collected. A control group (intact fish) was also sampled at the same time points. The effect of poly (I:C) on the expression of antioxidant and immune genes was time-of-day-dependent, and the response was stronger following poly (I:C) administration in the day than at night. Time-dependent differences were observed for some genes in the PBS and control groups. However, these differences were tissue-specific. In liver, almost all the genes were affected by time of day. In kidney, poly (I:C) affected the expression of all the gene markers regardless of administration time. These findings highlight the importance of considering the time to administer poly (I:C) when evaluating the fish immune response.

Keywords: Zebrafish; antioxidant response; daily rhythm; immune response; poly (I:C).