Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Sci Rep ; 14(1): 12450, 2024 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816571

RESUMO

The effects of low doses of ionizing radiation on atherosclerosis remain uncertain, particularly as regards the generation of pro- or anti-inflammatory responses, and the time scale at which such effects can occur following irradiation. To explore these phenomena, we exposed atheroprone ApoE(-/-) mice to a single dose of 0, 0.05, 0.5 or 1 Gy of 137Cs (γ) administered at a 10.35 mGy min-1 dose rate and evaluated short-term (1-10 days) and long-term consequences (100 days). Bone marrow-derived macrophages were derived from mice 1 day after exposure. Irradiation was associated with a significant skewing of M0 and M2 polarized macrophages towards the M2 phenotype, as demonstrated by an increased mRNA expression of Retnla, Arg1, and Chil3 in cells from mice exposed to 0.5 or 1 Gy compared with non-irradiated animals. Minimal effects were noted in M1 cells or M1 marker mRNA. Concurrently, we observed a reduced secretion of IL-1ß but enhanced IL-10 release from M0 and M2 macrophages. Effects of irradiation on circulating monocytes were most marked at day 10 post-exposure, when the 1 Gy dose was associated with enhanced numbers of both Ly6CHigh and Ly6Low cells. By day 100, levels of circulating monocytes in irradiated and non-irradiated mice were equivalent, but anti-inflammatory Ly6CLow monocytes were significantly increased in the spleen of mice exposed to 0.05 or 1 Gy. Long term exposures did not affect atherosclerotic plaque size or lipid content, as determined by Oil red O staining, whatever the dose applied. Similarly, irradiation did not affect atherosclerotic plaque collagen or smooth muscle cell content. However, we found that lesion CD68+ cell content tended to decrease with rising doses of radioactivity exposure, culminating in a significant reduction of plaque macrophage content at 1 Gy. Taken together, our results show that short- and long-term exposures to low to moderate doses of ionizing radiation drive an anti-inflammatory response, skewing bone marrow-derived macrophages towards an IL-10-secreting M2 phenotype and decreasing plaque macrophage content. These results suggest a low-grade athero-protective effect of low and moderate doses of ionizing radiation.


Assuntos
Radioisótopos de Césio , Raios gama , Macrófagos , Placa Aterosclerótica , Animais , Camundongos , Antígenos CD/metabolismo , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/deficiência , Aterosclerose/metabolismo , Aterosclerose/patologia , Molécula CD68 , Radioisótopos de Césio/uso terapêutico , Macrófagos/metabolismo , Macrófagos/efeitos da radiação , Camundongos Knockout , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Placa Aterosclerótica/radioterapia
2.
Euro Surveill ; 16(33)2011 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-21871230

RESUMO

In August 2011, a case of canine rabies was notified to the French veterinary services. The dog was a three-month-old puppy illegally imported from Morocco that presented behavioural changes on 1 August and was admitted to a veterinary clinic on 6 August. It died the following day and the body was shortly sent to the national reference centre where rabies was laboratory-confirmed on 11 August. Contact tracing and post-exposure treatment were initiated immediately.


Assuntos
Busca de Comunicante , Doenças do Cão/diagnóstico , Vírus da Raiva/isolamento & purificação , Raiva/diagnóstico , Animais , Comércio , Doenças do Cão/transmissão , Doenças do Cão/virologia , Cães , Técnica Direta de Fluorescência para Anticorpo , França , Humanos , Jurisprudência , Marrocos , Profilaxia Pós-Exposição , RNA Viral , Raiva/transmissão , Raiva/veterinária , Raiva/virologia , Viagem
3.
Dose Response ; 19(2): 15593258211016237, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163310

RESUMO

Low dose ionizing radiation (LDIR) is known to have a protective effect on atherosclerosis in rodent studies, but how it impacts different cells types involved in lesion formation remains incompletely understood. We investigated the immunomodulatory response of different doses and dose-rates of irradiation in ApoE-/- mice. Mice were exposed to external γ rays at very low (1.4 mGy.h-1) or low (50 mGy.h-1) dose-rates, with cumulative doses spanning 50 to 1000 mGy. Flow cytometry of circulating cells revealed a significant decrease in pro-inflammatory Ly6CHi monocytes at all cumulative doses at low dose-rate, but more disparate effects at very low dose-rate with reductions in Ly6CHi cells at doses of 50, 100 and 750 mGy only. In contrast, Ly6CLo monocytes were not affected by LDIR. Similarly, proportions of CD4+ T cell subsets in the spleen did not differ between irradiated mice and non-irradiated controls, whether assessing CD25+FoxP3+ regulatory or CD69+ activated lymphocytes. In the aorta, gene expression of cytokines such as IL-1 and TGF-ß and adhesion molecules such as E-Selectin, ICAM-1, and VCAM-1 were reduced at the intermediate dose of 200 mGy. These results suggest that LDIR may reduce atherosclerotic plaque formation by selectively reducing blood pro-inflammatory monocytes and by impairing adhesion molecule expression and inflammatory processes in the vessel wall. In contrast, splenic T lymphocytes were not affected by LDIR. Furthermore, some responses to irradiation were nonlinear; reductions in aortic gene expression were significant at intermediate doses, but not at either highest or lowest doses. This work furthers our understanding of the impact of LDIR with different dose-rates on immune system response in the context of atherosclerosis.

4.
Int J Radiat Biol ; 96(12): 1597-1607, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32990492

RESUMO

PURPOSE: Depleted uranium (DU) has several civilian and military applications. The effects of this emerging environmental pollutant on human health raise some concerns. Previous experimental studies have shown that uranium (U) exposure can disturb the central nervous system. A small quantity of U reaches the brain via the blood, but the effects on the blood-brain barrier (BBB) remain unclear. MATERIALS AND METHODS: In the present work, two cell culture models were exposed to DU for different times to study its cytotoxicity, paracellular permeability and extracellular concentration of U. The well-known immortalized human cerebral microvascular endothelial cells, hCMEC/D3, were cultured on the filter in the first model. In the second model, human primary cells of pericytes were cultured under the filter to understand the influence of cell environment after U exposure. RESULTS: The results show that U is not cytotoxic to hCMEC/D3 cells or pericytes until 500 µM (1.6 Bq.L-1). In addition, acute or chronic low-dose exposure of U did not disturb permeability and was conserved in both cell culture models. However, U is able to reach the brain compartment. During the first hours of exposure, the passage of U to the abluminal compartment was significantly reduced in the presence of pericytes. Electronic microscopy studies evidenced the formation of needlelike structures, like urchin-shaped precipitates, from 1 h of exposure. Analytical microscopy confirmed the U composition of these precipitates. Interestingly, precipitated U was detected only in endothelial cells and not in pericytes. U was localized in multilamellar or multivesicular bodies along the endo-lysosomal pathway, suggesting the involvement of these traffic vesicles in U sequestration and/or elimination. CONCLUSIONS: We show for the first time the in vitro passage of U across a human cerebral microvascular endothelial cells, and the intracellular localization of U precipitates without any cytotoxicity or modification of paracellular permeability. The difference between the results obtained with monolayers and co-culture models with pericytes illustrates the need to use complex in vitro models in order to mimic the neurovascular unit. Further in vivo studies should be performed to better understand the passage of U across the blood-brain barrier potentially involved in behavioral consequences.


Assuntos
Encéfalo/irrigação sanguínea , Células Endoteliais/metabolismo , Microvasos/citologia , Urânio/metabolismo , Barreira Hematoencefálica/metabolismo , Linhagem Celular , Técnicas de Cocultura , Células Endoteliais/efeitos da radiação , Espaço Extracelular/metabolismo , Espaço Extracelular/efeitos da radiação , Humanos , Permeabilidade , Fatores de Tempo
5.
Sci Rep ; 8(1): 17262, 2018 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30467388

RESUMO

Evaluation of the consequences of low to moderate doses of ionizing radiation (IR) remains a societal challenge, especially for children exposed to CT scans. Appropriate experimental models are needed to improve scientific understanding of how exposure of the postnatal brain to IR affects behavioral functions and their related pathophysiological mechanisms, considering brain complex functional organization. In the brain, the dorsal and ventral hippocampal dentate gyrus can be involved in distinct major behavioral functions. To study the long term behavioral effects of brain exposure at low to moderate doses of IR (doses range 0.25-1 Gy), we developed three new experimental models in 10-day-old mice: a model of brain irradiation and two targeted irradiation models of the dorsal and ventral dentate gyrus. We used the technological properties of the SARRP coupled with MR imaging. Our irradiation strategy has been twofold endorsed. The millimetric ballistic specificity of our models was first validated by measuring gamma-H2AX increase after irradiation. We then demonstrated higher anxiety/depressive-like behavior, preferentially mediate by the ventral part of the dentate gyrus, in mice after brain and ventral dentate gyrus IR exposure. This work provides new tools to enhance scientific understanding of how to protect children exposed to IR.


Assuntos
Comportamento Animal/efeitos da radiação , Encéfalo/diagnóstico por imagem , Giro Denteado/diagnóstico por imagem , Histonas/metabolismo , Animais , Animais Recém-Nascidos , Ansiedade/etiologia , Ansiedade/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Giro Denteado/metabolismo , Giro Denteado/efeitos da radiação , Depressão/etiologia , Depressão/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos da radiação , Imageamento por Ressonância Magnética , Masculino , Camundongos , Modelos Animais , Doses de Radiação
6.
Radiat Res ; 189(2): 187-196, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29227739

RESUMO

Populations living in radiation-contaminated territories, such as Chernobyl and Fukushima, are chronically exposed to external gamma radiation and internal radionuclide contamination due to the large amount of 137Cs released in the environment. The effect of chronic low-dose exposure on the development of cardiovascular diseases remains unclear. Previously reported studies have shown that low-dose radiation exposure could lead to discrepancies according to dose rate. In this study, we examined the effect of very low-dose and dose-rate chronic external exposure on atherosclerosis development. ApoE-/- mice were chronically irradiated with a gamma source for 8 months at two different dose rates, 12 and 28 µGy/h, equivalent to dose rates measured in contaminated territories, with a cumulative dose of 67 and 157 mGy, respectively. We evaluated plaque size and phenotype, inflammatory profile and oxidative stress status. The results of this study showed a decrease in plaque sizes and an increase in collagen content in ApoE-/- mice exposed to 28 µGy/h for 8 months compared to nonexposed animals. The plaque phenotype was associated with an increase in anti-inflammatory and anti-oxidative gene expression. These results suggest that chronic low-dose gamma irradiation induces an upregulation of organism defenses leading to a decrease in inflammation and plaque size. To our knowledge, this is the first study to describe the possible effect of chronic external very low-dose ionizing radiation exposure for 8 months. This work could help to identify the potential existence of a dose threshold, below that which harmful effects are not exhibited and beneficial effects are potentially observed. Furthermore, these findings permit consideration of the importance of dose rate in radiation protection.


Assuntos
Antioxidantes/metabolismo , Apolipoproteínas E/deficiência , Raios gama/efeitos adversos , Placa Aterosclerótica/metabolismo , Animais , Relação Dose-Resposta à Radiação , Inflamação/complicações , Masculino , Camundongos , Oxirredução/efeitos da radiação , Placa Aterosclerótica/complicações , Placa Aterosclerótica/patologia , Fatores de Tempo
7.
Toxicol Lett ; 282: 64-70, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29024790

RESUMO

INTRODUCTION: An increased health problem in industrialised countries is the contemporary concern of public and scientific community as well. This has been attributed in part to accumulated environmental pollutants especially radioactive substances and the use of nuclear power plants worldwide. However, the outcome of chronic exposure to low doses of a radionuclide such as uranium remains unknown. Recently, a paradigm shift in the perception of risk of radiotoxicology has emerged through investigating the possibility of transmission of biological effects over generations, in particular by epigenetic pathways. These processes are known for their crucial roles associated with the development of several diseases. OBJECTIVE: The current work investigates the epigenetic effect of chronic exposure to low doses of uranium and its inheritance across generations. Materials and Methods To test this proposition, a rodent multigenerational model, males and females, were exposed to a non-toxic concentration of uranium (40mgL-1 drinking water) for nine months. The uranium effects on were evaluated over three generations (F0, F1 and F2) by analysing the DNA methylation profile and DNMT genes expression in ovaries and testes tissues. RESULTS: Here we report a significant hypermethylation of testes DNA (p <0.005) whereas ovaries showed hypomethylated DNA (p <0.005). Interestingly, this DNA methylation profile was significantly maintained across generations F0, F1 and F2. Furthermore, qPCR results of both tissues imply a significant change in the expression of DNA methyltransferase genes (DNMT 1 and DNMT3a/b) as well. CONCLUSION: Altogether, our work demonstrates for the first time a sex-dependance and inheritance of epigenetic marks, DNA methylation, as a biological response to the exposure to low doses of uranium. However, it is not clear which type of reproductive cell type is more responsive in this context.


Assuntos
Metilação de DNA/efeitos da radiação , Epigênese Genética/efeitos da radiação , Ovário/efeitos da radiação , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Testículo/efeitos da radiação , Urânio/toxicidade , Animais , Relação Dose-Resposta à Radiação , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Masculino , Ovário/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Ratos , Caracteres Sexuais , Testículo/metabolismo
8.
Neurotoxicology ; 57: 153-162, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27639536

RESUMO

The developing brain is known to be sensitive to uranium (U) and exposure to this element during postnatal brain development results in behavioral disorders in adulthood. Moreover, we have previously shown that U exposure during gestation and lactation affects neurogenesis, in particular neural cell proliferation and cell death. In this study, we investigated whether exposure to depleted U (DU) affects neuronal differentiation during prenatal and postnatal brain development. We assessed in situ expression of specific genes involved in neuronal differentiation and expression of neuronal protein markers. The effects of DU on neurobehavioral function were investigated in parallel. Neuronal differentiation involves many signaling pathways that regulate the balance between cell proliferation and the transition to neuronal differentiation. In the present study pregnant rats were exposed from gestational day (GD) 1 throughout lactation to postnatal day (PND) 21. Using in situ hybridization, our results show decreased expression of Wnt3a in the hippocampal neuroepithelium in GD 13 embryos from DU exposed dams and decreased expression of Notch1 and increased expression of Mash1 in the hippocampal and dentate neuroepithelia of GD 18 fetuses from DU exposed dams. Expression of the NeuroD and NeuroD2 genes was not modified in the hippocampal neuroepithelium of GD18 fetuses from DU exposed dams. There was no change in the expression of any of these genes in the dentate gyrus of PND 5 pups from DU exposed dams. No change in nestin or doublecortin immunestaining was observed in the prenatal or early postnatal stages. However, the number of doublecortin-positive cells increased in the granular cell layer of PND 21 pups from DU exposed dams. Finally, depressive-like behavior was induced in PND21 rats, without modification of locomotor and exploratory activities or of spatial memory. In conclusion, these results showed that exposure of pregnant and lactating rats to DU affects brain development by causing disturbed cell proliferation and neuronal differentiation at the prenatal stage. Moreover, this exposure increased the pool of immature neurons in the dentate gyrus and induced depressive-like behavior in neonatal rats. Therefore, these data strongly suggest that exposure to DU during gestation and lactation affects brain development in embryos, fetuses and neonates with behavioral consequences in the offspring.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Giro Denteado , Depressão/etiologia , Neurônios/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Urânio/toxicidade , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Giro Denteado/citologia , Giro Denteado/efeitos dos fármacos , Giro Denteado/crescimento & desenvolvimento , Proteína Duplacortina , Embrião de Mamíferos , Comportamento Exploratório/efeitos dos fármacos , Feminino , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurogênese/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Natação/psicologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA