Assessment of the Central Effects of Natural Uranium via Behavioural Performances and the Cerebrospinal Fluid Metabolome

International audienceNatural uranium (NU), a component of the earth's crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.5, 10, or 40 mg⋅L −1 for male rats and 40 mg⋅L −1 for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg⋅L −1 NU. In male rats, spatial working memory and anxiety-and depressive-like behaviour were only altered by exposure to 40 mg⋅L −1 NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function

The brain is a target organ after acute exposure to depleted uranium

The health effects of depleted uranium (DU) are mainly caused by its chemical toxicity. Although the kidneys are the main target organs for uranium toxicity, uranium can also reach the brain. In this paper, the central effects of acute exposure to DU were studied in relation to health parameters and the sleep-wake cycle of adult rats. Animals were injected intraperitoneally with 144 ± 10 μg DU kg-1 as nitrate. Three days after injection, the amounts of uranium in the kidneys represented 2.6 μg of DU g-1 of tissue, considered as a sub-nephrotoxic dosage. The central effect of uranium could be seen through a decrease in food intake as early as the first day after exposure and shorter paradoxical sleep 3 days after acute DU exposure (-18% of controls). With a lower dosage of DU (70 ± 8 μg DU kg -1), no significant effect was observed on the sleep-wake cycle. The present study intends to illustrate the fact that the brain is a target organ, as are the kidneys, after acute exposure to a moderate dosage of DU. The mechanisms by which uranium causes these early neurophysiological perturbations shall be discussed. © 2005 Elsevier Ireland Ltd. All rights reserved

Effect of U and (137)Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat

International audienceFollowing the Chernobyl accident, the most significant problem for the population of the former Soviet Union for the next 50-70 years will be chronic internal contamination by radionuclides. One of the few experiments carried out in this field reported that neurotransmitter metabolism in the central nervous system of the rat was disturbed after feeding with oats contaminated by 137 Cs for 1 month. The present study assessed the effect of chronic contamination by depleted U or 137 Cs on the metabolism of two neurotransmitters in cerebral areas of rats. Dopamine and serotonin were chosen because their metabolism has been shown to be disturbed after external irradiation, even at moderate doses. Dopamine, serotonin, and some of their catabolites were measured by high-pressure liquid chromatography coupled with an electrochemical detector in five cerebral structures of rats contaminated over a 1-month period by drinking water (40 mg U·L –1 or 6500 Bq 137 Cs·L –1 ). In the striatum, hippocampus, cerebral cortex, thalamus, and cerebellum, the dopamine, serotonin, and catabolite levels were not significantly different between the control rats and rats contaminated by U or 137 Cs. These results are not in accordance with those previously described

Comparison of the effects of enriched uranium and 137-cesium on the behaviour of rats after chronic exposure

Purpose: A radionuclide that accumulates in the central nervous system is likely to exert both a chemical and a radiological effect. The present study aimed at assessing the behavioral effect of two radionuclides previously shown to accumulate in the central nervous system after chronic exposure - uranium and cesium. Materials and methods: Rats were exposed for 9 months to drinking water contaminated with either enriched uranium at a dosage of 40 mg U·l-1 or 137-cesium at a dosage of 6500 Bq·l-1, which correspond to the highest concentrations measured in some wells in the south of Finland (uranium) or in the milk in Belarus in the year following the Chernobyl accident (137-cesium). Results: At this level of exposure, 137-cesium had no effect on the locomotor activity measured in an open-field, on immobility time in a forced swimming test, on spontaneous alternation in a Y-maze and on novel object exploration in an object recognition test. Enriched uranium exposure specifically reduced the spontaneous alternation measured in the Y-maze after 3 and 9 months exposure although it did not affect the other parameters. Conclusion: Enriched uranium exposure altered the spatial working memory capacities and this effect was correlated with previously described accumulation of uranium in the hippocampus which is one of the cerebral areas involved in this memory system. © 2007 Informa UK Ltd

Impact de la masse de particules sur le comportement d'un moniteur de mesure de la contamination atmosphérique (cam)

International audienceCet article présente la caractérisation du comportement d'un moniteur de mesure de la contamination particulaire radioactive atmosphérique en condition de chantier de démantèlement simulée en laboratoire. Les premiers résultats présentés dans ce papier mettent en avant une mauvaise adaptation de la compensation dynamique du bruit de fond dans des conditions de fonctionnement non prises en compte dans les référentiels IEC

Chronic exposure to uranium leads to iron accumulation in rat kidney cells

After it is incorporated into the body, uranium accumulates in bone and kidney and is a nephrotoxin. Although acute or short-term uranium exposures are well documented, there is a lack of information about the effects of chronic exposure to low levels of uranium on both occupationally exposed people and the general public. The objective of this study was to identify the distribution and chemical form of uranium in kidneys of rats chronically exposed to uranium in drinking water (40 mg uranium liter-1). Rats were killed humanely 6, 9, 12 and 18 months after the beginning of exposure. Kidneys were dissected out and prepared for optical and electron microscope analysis and energy dispersive X-ray (XEDS) or electron energy loss spectrometry (EELS). Microscopic analysis showed that proximal tubule cells from contaminated rats had increased numbers of vesicles containing dense granular inclusions. These inclusions were composed of clusters of small granules and increased in number with the exposure duration. Using XEDS and EELS, these characteristic granules were identified as iron oxides. Uranium was found to be present as a trace element but was never associated with the iron granules. These results suggested that the mechanisms of iron homeostasis in kidney could be affected by chronic uranium exposure. © 2007 by Radiation Research Society

Chronic ingestion of uranyl nitrate perturbs acetylcholinesterase activity and monoamine metabolism in male rat brain

Recent animal studies have shown that uranium can reach the brain after chronic exposure. However, little information is available on the neurological effects of chronic long-term exposure to uranium. In the present study, the effects during 1.5, 6 and 9-month periods of chronic ingestion of uranyl nitrate (UN) in drinking water (40 mg of uranium per litre) on cholinergic acetylcholinesterase (AChE) activity and on dopaminergic and serotoninergic metabolisms were investigated in several areas of male Srague Dawley rat brains. Uranium brain accumulation and distribution was also investigated after 1.5 and 9 months. Both after 1.5, 6 and 9 months of exposure, AChE activity was unaffected in the striatum, hippocampus and frontal cortex. Nevertheless, AChE activity was transitionally perturbed in the cerebellum after 6 months of exposure. After 1.5 months of exposure, DA level increased in hypothalamus. After 6 months of exposure, a tiny but significant modification of the DAergic turnover ratio was detected in the frontal cortex. And after 9 months, UN produced a significant decrease in the 5HIAA level and the 5HTergic turn-over ratio in the frontal cortex and also a decrease in the DOPAC level and DAergic turn-over ratio in the striatum. Uranium brain accumulation was statistically significant in striatum after 1.5 months and in striatum, hippocampus and frontal cortex after 9 months of exposure. Although neurochemical changes did not always correlated with increased accumulation of uranium in specific areas, these results suggest that chronic ingestion of UN can cause chronic and progressive perturbations of physiological level of neurotransmitter systems. Considering previous reports on behavioural uranium-induced effects and the involvement of neurotransmitters in various behavioural processes, it would be crucial to determine whether these neurochemical disorders were accompanied by neurobehavioral deficits even at 40 mg of uranium per litre exposure. © 2005 Elsevier Inc. All rights reserved

Evaluation of the effect of chronic exposure to 137Cesium on sleep-wake cycle in rats

Since the Chernobyl accident, the most significant problem for the population living in the contaminated areas is chronic exposure by ingestion of radionuclides, notably 137Cs, a radioactive isotope of cesium. It can be found in the whole body, including the central nervous system. The present study aimed to assess the effect of 137Cs on the central nervous system and notably on open-field activity and the electroencephalographic pattern. Rats were exposed up to 90 days to drinking water contaminated with 137Cs at a dosage of 400 Bq kg-1, which is similar to that ingested by the population living in contaminated territories. At this level of exposure, no significant effect was observed on open-field activity. On the other hand, at 30 days exposure, 137Cs decreased the number of episodes of wakefulness and slow wave sleep and increased the mean duration of these stages. At 90 days exposure, the power of 0.5-4 Hz band of 137Cs-exposed rats was increased in comparison with controls. These electrophysiological changes may be due to a regional 137Cs accumulation in the brain stem. In conclusion, the neurocognitive effects of 137Cs need further evaluation and central disorders of population living in contaminated territories must be considered. © 2006 Elsevier Ireland Ltd. All rights reserved

Different pattern of brain pro-/anti-oxidant activity between depleted and enriched uranium in chronically exposed rats

Uranium is not only a heavy metal but also an alpha particle emitter. The main toxicity of uranium is expected to be due to chemiotoxicity rather than to radiotoxicity. Some studies have demonstrated that uranium induced some neurological disturbances, but without clear explanations. A possible mechanism of this neurotoxicity could be the oxidative stress induced by reactive oxygen species imbalance. The aim of the present study was to determine whether a chronic ingestion of uranium induced anti-oxidative defence mechanisms in the brain of rats. Rats received depleted (DU) or 4% enriched (EU) uranyl nitrate in the drinking water at 2 mg-1 kg-1 day-1 for 9 months. Cerebral cortex analyses were made by measuring mRNA and protein levels and enzymatic activities. Lipid peroxidation, an oxidative stress marker, was significantly enhanced after EU exposure, but not after DU. The gene expression or activity of the main antioxidant enzymes, i.e. superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), increased significantly after chronic exposure to DU. On the contrary, oral EU administration induced a decrease of these antioxidant enzymes. The NO-ergic pathway was almost not perturbed by DU or EU exposure. Finally, DU exposure increased significantly the transporters (Divalent-Metal-Transporter1; DMT1), the storage molecule (ferritin) and the ferroxidase enzyme (ceruloplasmin), but not EU. These results illustrate that oxidative stress plays a key role in the mechanism of uranium neurotoxicity. They showed that chronic exposure to DU, but not EU, seems to induce an increase of several antioxidant agents in order to counteract the oxidative stress. Finally, these results demonstrate the importance of the double toxicity, chemical and radiological, of uranium. © 2009 Elsevier Ireland Ltd. All rights reserved

Comparison of the effects of enriched uranium and 137-cesium on the behaviour of rats after chronic exposure

Purpose: A radionuclide that accumulates in the central nervous system is likely to exert both a chemical and a radiological effect. The present study aimed at assessing the behavioral effect of two radionuclides previously shown to accumulate in the central nervous system after chronic exposure - uranium and cesium. Materials and methods: Rats were exposed for 9 months to drinking water contaminated with either enriched uranium at a dosage of 40 mg U·l-1 or 137-cesium at a dosage of 6500 Bq·l-1, which correspond to the highest concentrations measured in some wells in the south of Finland (uranium) or in the milk in Belarus in the year following the Chernobyl accident (137-cesium). Results: At this level of exposure, 137-cesium had no effect on the locomotor activity measured in an open-field, on immobility time in a forced swimming test, on spontaneous alternation in a Y-maze and on novel object exploration in an object recognition test. Enriched uranium exposure specifically reduced the spontaneous alternation measured in the Y-maze after 3 and 9 months exposure although it did not affect the other parameters. Conclusion: Enriched uranium exposure altered the spatial working memory capacities and this effect was correlated with previously described accumulation of uranium in the hippocampus which is one of the cerebral areas involved in this memory system. © 2007 Informa UK Ltd