Induced torpor as a countermeasure for low dose radiation exposure in a zebrafish model
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ABSTRACT:
PROVIDER: PRJNA716978 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14060970.fastq.gz | Fastqsanger.gz | |||
| SRR14060971.fastq.gz | Fastqsanger.gz | |||
| SRR14060972_1.fastq.gz | Fastqsanger.gz | |||
| SRR14060972_2.fastq.gz | Fastqsanger.gz | |||
| SRR14060973_1.fastq.gz | Fastqsanger.gz |
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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
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 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.
2023-01-25 | GSE200212 | GEO
Project description:Induced Torpor: An Experimental Model to Investigate the Effects of Chronic Low-Dose Radiation Exposure on Zebrafish Liver
| PRJNA823689 | ENA
Project description:Low-dose radiation refers to exposure to ionizing radiation at levels that are generally considered safe and not expected to cause immediate health effects. However, the effects of low-dose radiation are still not fully understood and research in this area is ongoing. In this study, we investigated changes in gene expression in diabetic human aortic endothelial cells (T2D-HAECs) derived from type 2 diabetes patients. To this end, we used RNA-seq to profile the transcriptomes of cells exposed to varying doses of low-dose radiation (0.1Gy, 0.5Gy, and 2.0Gy) and compared them to a control group with no radiation exposure. Differentially expressed genes and enriched pathways were identified using the DESeq2 and gene set enrichment analysis (GSEA) methods, respectively. The data generated in this study are publicly available through the gene expression omnibus (GEO) database. This study provides a valuable resource for studying the effects of low-dose radiation on T2D-HAECs and can contribute to a better understanding of the potential human health risks associated with low-dose radiation exposure.
2023-04-07 | GSE228572 | GEO
Project description: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.
| S-EPMC8071006 | biostudies-literature
Project description:One of the most likely risks astronauts on long duration space missions face is exposure to ionizing radiation associated with highly energetic and charged heavy (HZE) particles. Since access to medical expertise on such a mission is limited at best, early diagnosis and mitigation of such exposure is critical. In order to accurately determine the time since exposure and dosage of exposure, dose- and time-dependent “biomarkers” are needed. Therefore, we performed a dose- and time-course transcriptional analysis for radiation exposure at 0, 0.15, 0.30, and 1.5 Gy with corresponding time points at 1 hour (hr) post-exposure as well as 2 hr and 6 hr using Affymetrix® Human PrimeArrayTM chips. The analysis of our data suggests a set of sensitive genetic biomarkers specific to each radiation level as well as generic radiation response biomarkers. Upregulated biomarkers can then be used within lab-on-a-chip (LOC) systems to detect exposure to ionizing radiation.
2017-12-01 | GSE63952 | GEO
Project description:Following nuclear accidents and the increasing use of radionuclides, environmental radiation radiological protection is a source of major concern, particularly in the context of low doses. Ionizing radiation (IR) may lead to genetic mutations, chromosomal rearrangements and epigenetic modifications. The present study focuses on the in vivo effects of low to moderate doses of IR on zebrafish early embryonic development. The effects of IR on the transcriptome were studied at the shield stage (6 hours post-fertilization, hpf) and at dose rates from 50 mGy/h to 0.005 mGy/h. The effects on the methylome by whole genome bisulfite sequencing were investigated at the same stage and at dose rates of 50 mGy/h and 5 mGy/h.IR exposure impacted the expression of genes involved in germ layers specification during gastrulation of zebrafish embryos. Moreover, changes in mitochondrial energetic metabolism were detected at all dose rates. Different transcriptomic responses were observed between groups irradiated at the two highest dose rates, 50 mGy/h and 5 mGy/h and those irradiated at the three lower dose rates. However, the transcriptomic analysis revealed an impact of IR on development, neurogenesis and muscular development at 50 mGy/h, 5 mGy/h and 0.5 mGy/h. The global level of methylation was not changed after exposure to IR, and no widespread changes in transposable elements were detected. Rather, we observed that IR induced loci specific demethylation in the promoter of genes involved in development, neurogenesis and myogenesis. Interestingly, this promoter hypomethylation was equally associated with a change in gene expression. In this study, both DMR and gene expression analysis pointed toward a specific deregulation of genes involved in development, neurogenesis and myogenesis. The modification of the methylation pattern in promoters of genes involved in central nervous system development and muscle development seems to be responsible of transcriptomic changes. This study confirms previous results obtained at later developmental stages, showing that neurogenesis and muscle development were also impacted at 50 mGy/h, 5 mGy/h and 0.5 mGy/h with phenotypic alterations in terms of muscle histology and swimming behaviour. This suggests that early developmental perturbations are predictive of functional defects at later developmental stages.
2020-06-29 | GSE146198 | GEO
Project description:The utilisation of synthetic torpor for interplanetary travel once seemed farfetched. However, mounting evidence points to torpor-induced protective benefits from the main hazards of space travel, namely, exposure to radiation and microgravity. To determine the radio-protective effects of an induced torpor-like state we exploited the ectothermic nature of the Danio rerio (zebrafish) in reducing their body temperatures to replicate the hypothermic states seen during natural torpor. We also administered melatonin as a sedative to reduce physical activity. Zebrafish were then exposed to low-dose radiation (0.3Gy) to simulate radiation exposure on long-term space missions. Transcriptomic analysis found that radiation exposure led to an upregulation of inflammatory and immune signatures and a differentiation and regeneration phenotype driven by STAT3 and MYOD1 transcription factors. In addition, DNA repair processes were downregulated in the muscle two days’ post-irradiation. The effects of hypothermia led to an increase in mitochondrial translation including genes involved in oxidative phosphorylation and a downregulation of ex-tracellular matrix and developmental genes. Upon radiation exposure, increases in endoplasmic reticulum stress genes were observed in a torpor+radiation group with downregulation of im-mune-related and ECM genes. Exposing hypothermic zebrafish to radiation also resulted in a downregulation of ECM and developmental genes however, immune/inflammatory related pathways were downregulated in contrast to that observed in the radiation only group. A cross-species comparison was performed with the muscle of hibernating Ursus arctos horribilis (brown bear) to define shared mechanisms of cold tolerance. Shared responses show an upregula-tion of protein translation and metabolism of amino acids, as well as a hypoxia response with the shared downregulation of glycolysis, ECM, and developmental genes.
2023-05-31 | GSE222614 | GEO
Project description:Many neural progenitor cells present in the fetus, but also in adult brain, which play a major role for the reproduction for healingin regeneration of neuronal cells, when differentiated cells are damaged. However, effects of radiation effect on undifferentiated neural progenitor cells remained unclear. The radiation doses of medical exposure, pollution by nuclear power plant accidents, and other exposure of workers; medical workers, airline crews, and astronaut have been focused. In this study, we report the effects of low- to middle- dose doses of radiation on cultured human neural progenitor cells (hNPC) differentiated derived from embryonic stem (ES) cells, which are partially compared with those of human umbilical vein endothelial cell (HUVEC). Gene expression was changed by continuous exposure of 31mGy; 0.0072 mGy/ minute, 124mGy; 0.029 mGy/ minute and 496mGy; 0.085 mGy/ minute for seventy-two hours. While shortening in neurite length by 124mGy was not significant, its decrease was observed by 496 mGy of radiation. Number of altered pathways increased dose-dependently. By thirty-one mGy per 72 hours of radiation, gene expression of inflammatory pathways involving interferon and cell junction were changed. By 124 mGy of radiation, DNA double strand break repair pathways and cell adhesion molecules were affected. Then, 496 mGy of radiation for 72 hours altered translational DNA synthesis pathway, apoptotic pathway, various metabolic pathways and neural differentiation pathways. Dose-dependent transcriptional changes by low- to middle- radiation are consistent with gradual axonal shortening, growth arrest and neural cell death.
2015-03-31 | GSE67309 | GEO
Project description:One of the most likely risks astronauts on long duration space missions face is exposure to ionizing radiation associated with highly energetic and charged heavy (HZE) particles. Since access to medical expertise on such a mission is limited at best, early diagnosis and mitigation of such exposure is critical. In order to accurately determine the dosage within 1 hour post-exposure, dose-dependent âbiomarkersâ are needed. Therefore, we performed a dose-course transcriptional analysis for radiation exposure at 0, 0.3, 1.5, and 3.0 Gy with corresponding time point at 1 hour (hr) post-exposure using Affymetrix® GeneChip® Human Gene 1.0 ST v1 Array chips. The analysis of our data suggests a set of sensitive genetic biomarkers specific to each radiation level as well as generic radiation response biomarkers. Upregulated biomarkers can then be used within lab-on-a-chip (LOC) systems to detect exposure to ionizing radiation. A total of sixteen human samples representing radiation exposure at levels 0 Gy, 0.3 Gy, 1.5 Gy and 3.0 Gy at time point 1 hour (hr) post-exposure were constructed. Blood samples were extracted from four human volunteers, and were irradiated. Leukocytes were extracted, and gene expression was measured. Samples for all four volunteers were measured at 1 hr for all four dose levels, resulting in four replicates at each dose level. Thus, a total of 4 samples at each of the four radiation levels were sampled, yielding the total of 16 samples.
2016-07-03 | E-GEOD-64375 | biostudies-arrayexpress