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International audience; The developing brain is more susceptible to neurotoxic compounds than adult brain. It is also well known that disturbances during brain development cause neurological disorders in adulthood. The brain is known to be a target organ of uranium (U) exposure and previous studies have noted that internal U contamination of adult rats induces behavioral disorders as well as affects neurochemistry and neurophysiological properties. In this study, we investigated whether depleted uranium (DU) exposure affects neurogenesis during prenatal and postnatal brain development. We examined the structural morphology of the brain, cell death and finally cell proliferation in animals exposed to DU during gestation and lactation compared to control animals. Our results showed that DU decreases cell death in the cortical neuroepithelium of gestational day (GD) 13 embryos exposed at 40. mg/L and 120. mg/L and of GD18 fetuses exposed at 120. mg/L without modification of the number of apoptotic cells. Cell proliferation analysis showed an increase of BrdU labeling in the dentate neuroepithelium of fetuses from GD18 at 120. mg/L. Postnatally, cell death is increased in the dentate gyrus of postnatal day (PND) 0 and PND5 exposed pups at 120. mg/L and is associated with an increase of apoptotic cell number only at PND5. Finally, a decrease in dividing cells is observed in the dentate gyrus of PND21 rats developmentally exposed to 120. mg/L DU, but not at PND0 and PND5. These results show that DU exposure during brain development causes opposite effects on cell proliferation and cell death processes between prenatal and postnatal development mainly at the highest dose. Although these modifications do not have a major impact in brain morphology, they could affect the next steps of neurogenesis and thus might disrupt the fine organization of the neuronal network.

In view of the known sensitivity of the developing central nervous system to pollutants, we sought to assess the effects of exposure to uranium (U) — a heavy metal naturally present in the environment — on the behavior of young rats and the impact of oxidative stress on their hippocampus. Pups drank U (in the form of uranyl nitrate) at doses of 10 or 40 mg.L-1 for 10 weeks from birth. Control rats drank mineral water. Locomotor activity in an open field and practice effects on a rotarod device decreased in rats exposed to 10 mg.L-1 (respectively, -19.4% and -51.4%) or 40 mg.L-1 (respectively, -19.3% and -55.9%) in compared with control rats. Anxiety (+37%) and depressive-like behavior (-50.8%) were altered by U exposure only at 40 mg.L-1. Lipid peroxidation (+35%) and protein carbonyl concentration (+137%) increased significantly after exposure to U at 40 mg.L-1. A significant increase in superoxide dismutase (SOD, +122.5%) and glutathione peroxidase (GPx, +13.6%) activities was also observed in the hippocampus of rats exposed to 40 mg.L-1. These results demonstrate that exposure to U since birth alters some behaviors and modifies antioxidant status. © 2015, Japanese Society of Toxicology. All rights reserved.

International audience; Strontium 90 (90Sr) remains in the environment long after a major nuclear disaster occurs. As a result, populations living on contaminated land are potentially exposed to daily ingesting of low quantities of 90Sr. The potential long-term health effects of such chronic contamination are unknown. In this study, we used a mouse model to evaluate the effects of 90Sr ingestion on the immune system, the animals were chronically exposed to 90Sr in drinking water at a concentration of 20 kBq/l, for a daily ingestion of 80-100 Bq/day. This resulted in a reduced number of CD19+ B lymphocytes in the bone marrow and spleen in steady-state conditions. In contrast, the results from a vaccine experiment performed as a functional test of the immune system showed that in response to T-dependent antigens, there was a reduction in IgG specific to tetanus toxin (TT), a balanced Th1/Th2 response inducer antigen, but not to keyhole limpet hemocyanin (KLH), a strong Th2 response inducer antigen. This was accompanied by a reduction in Th1 cells in the spleen, consistent with the observed reduction in specific IgG concentration. The precise mechanisms by which 90Sr acts on the immune system remain to be elucidated. However, our results suggest that 90Sr ingestion may be responsible for some of the reported effects of internal contamination on the immune system in civilian populations exposed to the Chernobyl fallout. © 2016 by Radiation Research Society.

Introduction Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake. Objectives In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L−1; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose–effect pattern and identify additional potential biomarkers in urine samples. Methods Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L−1). LC–MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages. Results The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L−1. Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score. Conclusion These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L−1. Electronic supplementary material The online version of this article (doi:10.1007/s11306-016-1092-8) contains supplementary material, which is available to authorized users.