Multi-level approach for the study of air pollution impact on health

Diesel exhaust particles (DEP), a major component of traffic-related air pollution, are emerging as key factors to adverse health effects in terms of neuroinflammation and oxidative stress. This study represents a model for multi-level investigations into environmental health risks, exploring the systemic impact of DEP exposure in healthy and disease-relevant mouse models, exploiting a physiological pollutant administration route (inExpose® system) and an in vivo molecular imaging combined with epigenomic analysis for the readout. For this study, healthy male C57Bl/6 mice (n=10) were divided into saline (controls, n=2), low-dose (n=4, 1,5 mg/ml) and high-dose (n=4, 3 mg/ml) DEP exposure. The day after nose-only single-dose exposure of 15 minutes, all animals underwent whole-body PET/CT scans with [18F]FDG, as a marker of metabolism and inflammation, and were sacrificed thereafter for blood and organs collection for miRNA profiling with RT-PCR. Radiotracer uptake at the organ level was quantified as standardized uptake value (SUVmean). Mice exposed to DEP showed an increased FDG uptake in lung compared to the controls that would appear to be dose dependent. Transcriptomic analysis revealed upregulation of cerebral TGF- after low-dose and high-dose DEP exposure. Alteration in microRNA profiling was observed in both brain and lung tissue, highlighting a role of miRNA involved in inflammatory pathways (inflamma-miR) in the response to DEP exposure.