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Inhalation of tungsten particles: impact on the central nervous system, an unsuspected target organ
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International audience. Being the main cause of contamination in nuclear facilities, particulate aerosols represent a health risk factor raising serious concerns. The brain represents a direct target for inhaled aerosols, in particular through the involvement of the olfactory nerve entry pathway. There is a lack of knowledge about the toxicity of tungsten (W) in the central nervous system, although it is considered as an emerging contaminant. To study the potential effects of exposure to W particles, preliminary metrological work was carried out to optimize and control the generation of the aerosol at concentrations in the order of the Occupational Exposure Limit Value, and to characterize its granulometry. Adult rats were exposed to optimized and controlled W aerosols via inhalation at two different concentrations (5 and 80 mg.m-3) in a single acute or fractionated mode (4X daily exposures). Various assays were used to examine biological processes involved in brain toxicity, such as neuroinflammation, oxidative stress, cell death and neurogenesis.Results obtained 24 hours after exposure suggest site-specific and concentration-dependent modifications of the transcripts of genes involved in these target processes. The impact of oxidative stress is currently being further evaluated using the Dihydroethidium probe sensitive to reactive oxygen species, complemented by immunohistochemistry and protein expression of 4HNE and Nrf2, which respectively reflect lipid peroxidation and antioxidant signalling. Immunohistochemistry experiments suggest a potential effect on the density and morphology of microglial cells involved in neuroinflammation, as well as an abnormal phenotype of the nuclei of some mature neurons indicating neuronal damage. At the cellular level, the effects were also site-specific, dependent on the mode of exposure and the concentration and could involve several signalling pathways, recently investigated by transcriptomics. ICP-MS assays show an increase in the concentration of W in brain structures in groups exposed to high concentrations, which could contribute to site-specificity of observed effects. Current work aims to investigate whether these effects are related to adaptive mechanisms or are neurotoxic and can ultimately alter neuronal integrity depending on exposure patterns. Co-exposure to W aerosols and ionizing radiation is another focus for our future research.These results can help close knowledge gaps in understanding neurological health effects of particulate aerosols, especially metallic ones, and thus help improve the system of human (radio)protection.
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