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International audience; Background: Health risk issues are raised concerning inhalation of particulate pollutants that are thought to have potential hazardous effects in the central nervous system. The brain is presented as a direct target of particulate matter exposure because of the “nose-to-brain” pathway involvement. The main cause of contamination in nuclear occupational activities is related to exposure to aerosols containing radionuclides, in particular uranium dust. It has been previously demonstrated that instilled solubilized uranium in the rat nasal cavity is conveyed to the brain via the olfactory nerve. Objective: The aim of this study was to analyze the anatomical localization of uranium compounds in the olfactory system after in vivo exposure to a polydisperse aerosol of uranium tetraoxide (UO4) particles.Methods: The olfactory neuroepithelium and selected brain structuresolfactory bulbs, frontal cortex, hippocampus, cerebellum and brainstemwere microdissected four hours after aerosol inhalation via a nose-only system in adult rats. Tissues were subjected to complementary analytical techniques.Results: Uranium concentrations measured by ICP-MS were significantly higher in all brain structures from exposed animals compared to their respective controls. We observed that cerebral uranium concentrations followed an antero-posterior gradient with typical accumulation in the olfactory bulbs, characteristic of a direct olfactory transfer of inhaled compounds. Secondary Ion Mass Spectrometry microscopy and Transmission Electron Microscopy coupled to Energy Dispersive X-Ray spectroscopy were used in order to track elemental uranium in situ in the olfactory epithelium. Elemental uranium was detected in precise anatomical regions: olfactory neuron dendrites, paracellular junctions of neuroepithelial cells, olfactory nerve tracts (around axons and endoneural spaces).Conclusion: These neuroanatomical observations in a rat model are consistent with the transport of elemental uranium in different physico-chemical forms (solubilized, nanoparticles) along olfactory nerve bundles after inhalation of UO4 microparticles. This work contributes to knowledge of the mechanistic actions of particulate pollutants on the brain.

International audience; Uranium is a heavy metal naturally present in the environment that may be chronically ingested by the population. Previous studies have shown that uranium is present in the brain and alters behaviour, notably locomotor activity, sensorimotor ability, sleep/wake cycle and the memory process, but also metabolism of neurotransmitters. The cholinergic system mediates many cognitive systems, including those disturbed after chronic exposure to uranium i.e., spatial memory, sleep/wake cycle and locomotor activity. The objective of this study was to assess whether these disorders follow uranium-induced alteration of the cholinergic system. In comparison with 40 control rats, 40 rats drank 40 mg/L uranyl nitrate for 1.5 or 9 months. Cortex and hippocampus were removed and gene expression and protein level were analysed to determine potential changes in cholinergic receptors and acetylcholine levels. The expression of genes showed various alterations in the two brain areas after short- and long-term exposure. Nevertheless, protein levels of the choline acetyltransferase enzyme (ChAT), the vesicular transporter of acetylcholine (VAChT) and the nicotinic receptor beta2 sub-unit (nAChRbeta2) were unmodified in all cases of the experiment and muscarinic receptor type 1 (m1AChR) protein level was disturbed only after 9 months of exposure in the cortex (-30%). Acetylcholine levels were unchanged in the hippocampus after 1.5 and 9 months, but were decreased in the cortex after 1.5 months only (-22%). Acetylcholinesterase (AChE) activity was also unchanged in the hippocampus but decreased in the cortex after 1.5 and 9 months (-16% and -18%, respectively). Taken together, these data indicate that the cholinergic system is a target of uranium exposure in a structure-dependent and time-dependent manner. These cholinergic alterations could participate in behavioural impairments.