Revealing the increased stress response behavior through transcriptomic analysis of adult zebrafish brain after chronic and low to moderate dose rates of ionizing radiations
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE206573 | GEO | 2022/08/17
REPOSITORIES: GEO
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Project description:High levels of ionizing radiation (IR) are known to induce neurogenesis defects with harmful consequences on brain morphogenesis and cognitive functions, but the effects of chronic low to moderate dose rates of IR remain largely unknown. In this study, we aim at defining the main molecular pathways impacted by IR and how these effects can translate to higher organizational levels such as behavior. Adult zebrafish were exposed to gamma radiation for 36 days at 0.05 mGy/h, 0.5 mGy/h and 5 mGy/h. RNA sequencing was performed on the telencephalon and completed by RNA in situ hybridization that confirmed the upregulation of oxytocin and cone rod homeobox in the parvocellular preoptic nucleus. A dose rate-dependent increase in differentially expressed genes (DEG) was observed with 27 DEG at 0.05 mGy/h, 200 DEG at 0.5 mGy/h and 530 DEG at 5 mGy/h. Genes involved in neurotransmission, neurohormones and hypothalamic-pituitary-interrenal axis functions were specifically affected, strongly suggesting their involvement in the stress response behavior observed after exposure to dose rates superior or equal to 0.5 mGy/h. At the individual scale, hypolocomotion, increased freezing and social stress were detected. Together, these data highlight the intricate interaction between neurohormones (and particularly oxytocin), neurotransmission and neurogenesis in response to chronic exposure to IR and the establishment of anxiety-like behavior.
| S-EPMC9367516 | biostudies-literature
Project description:Revealing the increased stress response behavior through transcriptomic analysis of adult zebrafish brain after chronic and low to moderate dose rates of ionizing radiations
| PRJNA851399 | ENA
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:Lymphocytes are the standard cell of a majority of biodosimetry approaches because of their availability and radiosensitivity. But progresses remain to be performed to bring down the minimum threshold of dose sensitivity. To find a lymphocyte subtype able to respond to low doses of ionizing radiation, we examined gene expression variations in different lymphocyte subpopulations using the microarray technology. Blood samples were independently exposed to 0, 0.05 and 0.5 Gray of ionizing radiations. Three and 24 hours after exposure, CD56+, CD4+ and CD8+ cells were negatively isolated. RNA from each condition was competitively hybridized on oligonucleotide microarrays. Keywords: Dose response, stress response, cell type comparison
2008-02-01 | GSE6978 | GEO
Project description:Human exposure to low-to-moderate dose ionizing radiation (LMD-IR) is increasing via environmental, medical, occupational sources. Acute exposure to LMD-IR can cause subclinical damage to cells, resulting in altered gene expression and cellular function within the human brain. It has been difficult to identify diagnostic and predictive biomarkers of exposure using traditional research models due to factors including lack of 3D structure in monolayer cell cultures, limited ability of animal models to accurately predict human responses, and technical limitations of studying functional human brain tissue. To address this gap, we generated brain/cerebral organoids from human induced pluripotent stem cells to study the radiosensitivity of human brain cells, including neurons, astrocytes, and oligodendrocytes. While organoids have become popular models for studying brain physiology and pathology, there is little evidence to confirm that exposing brain organoids to LMD-IR will recapitulate previous in vitro and in vivo observations. We hypothesized that exposing brain organoids to proton radiation would (1) cause a time- and dose-dependent increase in DNA damage, (2) induce cell type-specific differences in radiosensitivity, and (3) increase expression of oxidative stress and DNA damage response genes. Organoids were exposed to 0.5 or 2 Gy of 250 MeV protons and samples were collected at 30 minute, 24 hour, and 48 hour timepoints. Using immunofluorescence and RNA sequencing, we found time- and dose-dependent increases in DNA damage in irradiated organoids; no changes in cell populations for neurons, oligodendrocytes, and astrocytes by 24 hours; decreased expression of genes related to oligodendrocyte lineage, astrocyte lineage, mitochondrial function, and cell cycle progression by 48 hours; increased expression of genes related to neuron lineage, oxidative stress, and DNA damage checkpoint regulation by 48 hours. Our findings demonstrate the possibility of using organoids to characterize cell-specific radiosensitivity and early radiation-induced gene expression changes within the human brain, providing new avenues for further study of the mechanisms underlying acute neural cell responses to IR exposure at low-to-moderate doses.
| S-EPMC10231836 | biostudies-literature
Project description:Lymphocytes are the standard cell of a majority of biodosimetry approaches because of their availability and radiosensitivity. But progresses remain to be performed to bring down the minimum threshold of dose sensitivity. To find a lymphocyte subtype able to respond to low doses of ionizing radiation, we examined gene expression variations in different lymphocyte subpopulations using the microarray technology. Blood samples were independently exposed to 0, 0.05 and 0.5 Gray of ionizing radiations. Three and 24 hours after exposure, CD56+, CD4+ and CD8+ cells were negatively isolated. RNA from each condition was competitively hybridized on oligonucleotide microarrays. Keywords: Dose response, stress response, cell type comparison We characterized genes whose expression level was affected following exposure to γ rays by carrying out genome-wide expression profiling on each lymphocyte subpopulation. Total blood samples were collected from 5 healthy male donors. Each sample was splitted into three parts which were exposed respectively to 0 Gy (sham-irradiated), 0.05 Gy and 0.5 Gy of ionizing radiations. Lymphocytes subpopulations were sorted 3 and 24 hours after irradiation. RNA was prepared from each cell type and amplified. The amino-allyl amplified RNAs were labeled and independently hybridized to the array. RNA from MNC obtained from 20 independent healthy donors constituted the reference group for competitive oligonucleotide microarray hybridization. According to our criteria of quality, we considered a total of 114 microarrays
2008-01-31 | E-GEOD-6978 | biostudies-arrayexpress
Project description:We demonstrate that low-dose ionizing radiation from X-rays drives metabolic activation in microalgae. We exploited this phenomenon to develop a method for increased lipid yield in stationary phase Chlorella sorokiniana cultures by 25% in just 24 hours, caused by a reproducible metabolic response that includes up-regulation of >30 lipid metabolism genes. This approach avoids the need to modify the strain or cultivation conditions, and does not affect cell viability or biomass.
2024-06-06 | E-MTAB-12288 | biostudies-arrayexpress
Project description:There is increasing interest in the effects of low-dose ionizing radiation (IR) on plants as might occur during spaceflight, or as a consequence of human activities, such as nuclear power generation, that may result in the release of radioactive materials into the environment. High doses of IR have long been used for the induction of mutations in plants with the goal of generating desirable traits for agribusiness. However, less is known about the responses of plants to acute low doses of IR exposure. Here, we take a multi-omics approach to characterize the response to low dose IR in A. thaliana. We adapt the Methyltransferase Accessibility Protocol for individual templates (MAPit) technique for use in plants allowing us to assay the epigenetic response to acute low-dose IR (10 cGy and 100 cGy) 72 hr after exposure, and, in parallel, use RNA sequencing to profile the transcription response at 1, 3, 24 and 72 hr after exposure. We observe that IR exposures as low as 10 cGy elicit robust genetic responses in Arabidopsis thaliana detectable as early as 1 hr after exposure. Examination of these responses revealed dose-dependent changes in gene expression, chromatin accessibility and DNA methylation that implicate the ethylene signalling pathway and response to abiotic stress as underlying the transcriptional and epigenetic changes associated with IR. These changes are observable up to 72 hr after exposure suggesting that they are maintained well after the initial acute exposure. Our findings indicate that A. thaliana executes a coordinated, multi-modal response to low-dose IR through induction and regulation of the ethylene response pathway.
2024-08-31 | GSE237550 | GEO
Project description:Alzheimer's disease (AD) is the most common cause of dementia. The neuropathological features of AD include amyloid-β (Aβ) deposition and hyperphosphorylated tau accumulation. Although several clinical trials have been conducted to identify a cure for AD, no effective drug or treatment has been identified thus far. Recently, the potential use of non-pharmacological interventions to prevent or treat AD has gained attention. Low-dose ionizing radiation (LDIR) is a non-pharmacological intervention which is currently being evaluated in clinical trials for AD patients. However, the mechanisms underlying the therapeutic effects of LDIR therapy have not yet been established. In this study, we examined the effect of LDIR on Aβ accumulation and Aβ-mediated pathology. To investigate the short-term effects of low-moderate dose ionizing radiation (LMDIR), a total of 9 Gy (1.8 Gy per fraction for five times) were radiated to 4-month-old 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD, and then sacrificed at 4 days after last exposure to LMDIR. Comparing sham-exposed and LMDIR-exposed 5XFAD mice indicated that short-term exposure to LMDIR did not affect Aβ accumulation in the brain, but significantly ameliorated synaptic degeneration, neuronal loss, and neuroinflammation in the hippocampal formation and cerebral cortex. In addition, a direct neuroprotective effect was confirmed in SH-SY5Y neuronal cells treated with Aβ1-42 (2 μM) after single irradiation (1 Gy). In BV-2 microglial cells exposed to Aβ and/or LMDIR, LMDIR therapy significantly inhibited the production of pro-inflammatory molecules and activation of the nuclear factor-kappa B (NF-κB) pathway. These results indicate that LMDIR directly ameliorated neurodegeneration and neuroinflammation in vivo and in vitro. Collectively, our findings suggest that the therapeutic benefits of LMDIR in AD may be mediated by its neuroprotective and anti-inflammatory effects.
| S-EPMC7279400 | biostudies-literature
Project description:Irradiated cell lines exposed to 1-10 Gy
2010-07-01 | GSE22639 | GEO