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Background: Health-risk issues are raised concerning inhalation of particulate pollutants that are thought to have potential hazardous effects on the central nervous system. The brain is presented as a direct target of particulate matter (PM) 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, particularly 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 (OE) and selected brain structures—olfactory bulbs (OB), frontal cortex (FC), hippocampus (HIP), cerebellum (Cer), and brainstem (BS)—were microdissected 4 h after aerosol inhalation via a nose-only system in adult rats. Tissues were subjected to complementary analytical techniques. Results: Uranium concentrations measured by inductively coupled plasma mass spectrometry (ICP-MS) were significantly higher in all brain structures from exposed animals compared with their respective controls. We observed that cerebral uranium concentrations followed an anteroposterior gradient with typical accumulation in the OB, characteristic of a direct olfactory transfer of inhaled compounds. Secondary ion mass spectrometry (SIMS) microscopy and transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy (TEM-EDX) 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, and 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 physicochemical 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. https://doi.org/10.1289/EHP4927

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.