Inhalation of nanoplastics in the mouse model: tissue biodistribution and effects on the olfactory system

Nanoplastics (NPs) are increasingly distributed in almost all ecosystems. Soil, air and water are not spared from this massive contamination that determines for various organisms, including humans, the presence of different routes of exposure to NPs, such as the food chain, water and air. Knowledge on the effects of NPs inhalation in mammals is still rather scarce, so the goal of our research is to evaluate the effects of NPs airborne administration on the mouse brain. For this purpose, adult mice were exposed via aerosol for 3 hours a day during 7 days to an aerosol solution containing polystyrene nanoplastics (PS-NPs with a diameter=100 nm) labelled with a red fluorophore. At the end of the NPs administration via aerosol, animals were subjected to an olfactory task (Odor detection threshold) and to pletismography to evaluate olfactory and respiratory parameters, respectively. After the sacrifice, we performed an ex-vivo analysis with a fluorescence optical imaging system to detect the bio-distribution of NPs in the different organs of mice and to evaluate any changes in distribution over time in specific tissues. By this analysis we found a presence of PS-NPs in the brain, lungs, testes and fat. Accumulation over time was detected exclusively in the lungs and fat. Plethysmograph analysis also highlighted a loss of lung function in mice exposed to NPs. Given the route of exposure employed, our work focused on studying the olfactory bulb (OB) and the subventricular zone, which supplies a continuous flow of new neurons to the OB. We found that PS-NPs exposure disrupted olfactory sensitivity for a specific odorant. We also observed a decrease in c-fos+ cells in olfactory bulb after an olfactory stimulation, thus suggesting that PS-NPs exposure may interfere with olfactory bulb functionality. Our data showed an activation of microglia within the OB of mice treated with PS-NPs, indicating the presence of pro-inflammatory phenomena. We also detected an upregulation of TYROBP, a microglial gene related to inflammatory-related phagocytosis. Finally, we observed that inhalation of NPs induced a strong increase of subventricular neurogenesis compared to control mice. These data lead us to hypothesize that NPs inhalation may alter the homeostasis and functionality of the OB with a consequent compensatory action by subventricular neurogenesis. Further molecular, cellular and functional studies are underway to verify this hypothesis.