Investigating the effects of chronic low-dose radiation exposure in the liver of a hypothermic zebrafish model

Cahill, Thomas; Abraham da Silveira, Willian; Renaud, Ludivine; Wang, Hao; Williamson, Tucker; Chung, Dongjun; Chan, Sherine; Overton, Ian; Hardiman, Gary

Abstract

Mankind's quest for a manned mission to Mars is placing increased emphasis on the development of innovative radio-protective countermeasures for long-term space travel. Hibernation confers radio-protective effects in hibernating animals, and this has led to the investigation of synthetic torpor to mitigate the deleterious effects of chronic low-dose-rate radiation exposure. Here we describe an induced torpor model we developed using the zebrafish. We explored the effects of radiation exposure on this model with a focus on the liver. Transcriptomic and behavioural analyses were performed. Radiation exposure resulted in transcriptomic perturbations in lipid metabolism and absorption, wound healing, immune response, and fibrogenic pathways. Induced torpor reduced metabolism and increased pro-survival, anti-apoptotic, and DNA repair pathways. Coupled with radiation exposure, induced torpor led to a stress response but also revealed maintenance of DNA repair mechanisms, pro-survival and anti-apoptotic signals. To further characterise our model of induced torpor, the zebrafish model was compared with hepatic transcriptomic data from hibernating grizzly bears (Ursus arctos horribilis) and active controls revealing conserved responses in gene expression associated with anti-apoptotic processes, DNA damage repair, cell survival, proliferation, and antioxidant response. Similarly, the radiation group was compared with space-flown mice revealing shared changes in lipid metabolism.

• Journal Article Type: Article
• Acceptance Date: Jan 1, 2023
• Online Publication Date: Jan 17, 2023
• Publication Date: Jan 17, 2023
• Deposit Date: Oct 25, 2024
• Publicly Available Date: Oct 28, 2024
• Journal: Scientific Reports
• Print ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 1
• Article Number: 918
• DOI: https://doi.org/10.1038/s41598-022-26976-4
• Additional Information: Received: 8 August 2022; Accepted: 22 December 2022; First Online: 17 January 2023; : G.H. is a founder of Altomics Datamation Ltd. and a member of its scientific advisory board. SC is CEO and a founder of Neuroene Therapeutics. The other authors declare that they have no competing interests.