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Article

Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model

1
School of Biological Sciences & Institute for Global Food Security, Queens University Belfast, Belfast BT9 5DL, UK
2
Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
3
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
4
Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA
5
Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast BT9 7AE, UK
*
Author to whom correspondence should be addressed.
Joint first authors.
Academic Editor: Natascia Tiso
Cells 2021, 10(4), 906; https://doi.org/10.3390/cells10040906
Received: 31 January 2021 / Revised: 7 April 2021 / Accepted: 11 April 2021 / Published: 14 April 2021
(This article belongs to the Special Issue Signaling Pathway Analysis and Disease Modeling in Zebrafish)
The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique challenges including exposure to ionising radiation from galactic cosmic rays and potential solar particle events, exposure to microgravity and specific nutritional challenges arising from earth independent exploration. Ionising radiation is one of the major obstacles facing future space travel as it can generate oxidative stress and directly damage cellular structures such as DNA, in turn causing genomic instability, telomere shortening, extracellular-matrix remodelling and persistent inflammation. In the gastrointestinal tract (GIT) this can lead to leaky gut syndrome, perforations and motility issues, which impact GIT functionality and affect nutritional status. While current countermeasures such as shielding from the spacecraft can attenuate harmful biological effects, they produce harmful secondary particles that contribute to radiation exposure. 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 reduced temperature, and radiation exposure was administered twice over the course of 10 days. The protective effects of induced-torpor were assessed via RNA sequencing and qPCR of mRNA extracted from the GIT. Pathway and network analysis were performed on the transcriptomic data to characterise the genomic signatures in radiation, torpor and torpor + radiation groups. Phenotypic analyses revealed that melatonin and reduced temperature successfully induced a torpor-like state in zebrafish as shown by decreased metabolism and activity levels. Genomic analyses indicated that low dose radiation caused DNA damage and oxidative stress triggering a stress response, including steroidal signalling and changes to metabolism, and cell cycle arrest. Torpor attenuated the stress response through an increase in pro-survival signals, reduced oxidative stress via the oxygen effect and detection and removal of misfolded proteins. This proof-of-concept model provides compelling initial evidence for utilizing an induced torpor-like state as a potential countermeasure for radiation exposure. View Full-Text
Keywords: torpor; countermeasure; space; radiation; zebrafish; metabolism; temperature; signalling pathways; transcriptome; bioinformatics torpor; countermeasure; space; radiation; zebrafish; metabolism; temperature; signalling pathways; transcriptome; bioinformatics
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MDPI and ACS Style

Cahill, T.; da Silveira, W.A.; Renaud, L.; Williamson, T.; Wang, H.; Chung, D.; Overton, I.; Chan, S.S.L.; Hardiman, G. Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model. Cells 2021, 10, 906. https://doi.org/10.3390/cells10040906

AMA Style

Cahill T, da Silveira WA, Renaud L, Williamson T, Wang H, Chung D, Overton I, Chan SSL, Hardiman G. Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model. Cells. 2021; 10(4):906. https://doi.org/10.3390/cells10040906

Chicago/Turabian Style

Cahill, Thomas, Willian A. da Silveira, Ludivine Renaud, Tucker Williamson, Hao Wang, Dongjun Chung, Ian Overton, Sherine S.L. Chan, and Gary Hardiman. 2021. "Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model" Cells 10, no. 4: 906. https://doi.org/10.3390/cells10040906

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