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Induced Torpor: An Experimental Model to Investigate the Effects of Chronic Low-Dose Radiation Exposure on Zebrafish Liver

ABSTRACT: 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 temperatures, 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 liver. A systems-level analysis was performed on the transcriptomic data to characterise the cellular phenotypes in radiation (28.5-rad), temperature+melatonin (18.5-mel), temperature+radiation (18.5-rad), and temperature+melatonin+radiation (18.5-mel-rad) groups compared with a control group (28.5-Ctrl). The results revealed that the torpor group experiences a reduction in metabolic genes, and increased pro-survival, antiapoptotic and DNA repair genes. The radiation group had changes to lipid metabolism and absorptions, a wound healing response and an immune response. While the induced torpor group showed a response to stress including changes to metabolism and perturbation of the circadian rhythm, it also maintained the pro-survival, anti-apoptotic and DNA repair genes seen in the torpor group suggesting a conferred radio-protective effect.

ORGANISM(S): Danio rerio

PROVIDER: GSE200212 | GEO | 2023/01/25

REPOSITORIES: GEO

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

Project description: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.

2021-04-28 | GSE169522 | GEO

Transcriptome Profiling Reveals Enhanced Mitochondrial Activity as a Cold Adaptive Strategy to Hypothermia in Zebrafish Muscle

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Estrogen-Sensitive Medial Preoptic Area Neurons Coordinate Hypothermia and Hypometabolism in Mice

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Project description:Despite the fact that we are constantly exposed to various environmental compounds, very few studies explore the impact of combined exposure to physical and chemical pollutants on reproductive health. Until now, assessment of pollutants is mostly based on the evaluation of single pollutant or combination of chemicals with common features and modes of action. In this context, numerous studies have demonstrated that steroidogenesis and gametogenesis, the main testicular functions, are well-known to be sensitize by endocrine disruptors (as Bisphenol A) and DNA-damaging agents (as γ-rays) respectively. In this study, we aim to investigate short and long term testicular transcriptionnal alterations of combined fetal exposure to well-known environmental toxicants: γ-rays (RAD) and BPA. To discriminate specific signatures of BPA or RAD exposure after combined exposure and evidence the type of synergisms between this pollutants, we performed transcriptomic analyses on testis exposed to BPA or RAD alone and co-exposed with BPA and RAD and compared gene expression with control condition. For this, we exposed pregnant mice from 10.5 dpc to 18.5 dpc to 10µM of BPA (in drinking water) and/or we irradiated mice at 12.5 dpc to 0.2 Gy. We performed transcriptomic analyses on fetal testis (18.5 dpc) and adult testis (3 months) to evaluate short and long term cell response after in utero exposure.

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2006-10-01 | GSE4880 | GEO

Dynamic Temperature-Sensitive A-to-I RNA editing in the Brain of a Heterothermic Mammal during Hibernation

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