Induced torpor as a countermeasure for low dose radiation exposure in a zebrafish model

We hypothesised that induction of a torpor-like state would confer a radioprotective effect given the evidence that hibernation extends survival times in irradiated squirrels compared to active controls. To test this hypothesis, a torpor-like state was induced in zebrafish using melatonin treatment and cold temperature, and radiation exposure was administered twice over the course of 10 days. The protective effects of induced-torpor were assessed via RNA sequencing of mRNA extracted from the GIT. A systems level analysis was performed on the transcriptomic data to characterise the cellular phenotypes in radiation, torpor, and torpor+radiation groups. The results revealed that melatonin and cold temperature successfully induced a torpor-like state in zebrafish as shown by decreased metabolism and activity levels. Low dose radiation caused DNA damage and oxidative stress triggering a stress response, including steroidal signalling and changes to metabolism, damage to the central nervous system and cell cycle arrest. This stress response was attenuated in the torpor+radiation group by an increase in biosynthesis, proliferation, cell survival signals and expression of genes involved in protection against the adverse effects of radiation, particularly in neurons, suggesting a radioprotective effect conferred by a torpor state. This proof-of-concept model provides compelling initial evidence for utilizing an induced torpor-like state as a potential countermeasure for radiation exposure. Transcriptomic analysis of zebrafish GIT assessing the protective effects of induced torpor on the harmful effects of low dose radiation