Subchronic, low-frequency polystyrene microplastic or nanoplastic exposure elicits molecular perturbations but...

The global public concerns about micro- and nanoplastics (MNPs) are on the rise, whereas the mechanisms underlying MNP-mediated toxicity have not been fully elucidated. In particular, toxic responses in the gut-brain axis of mice varied across studies due to the high variability in experimental exposure designs. Thus, we employed a mouse model (n = 46) with a standardized exposure regimen of 0.3 mg per treatment, administered twice weekly for 12 consecutive weeks, to systematically evaluate MP (5 μm) and NP (0.5 μm) induced toxicity in both the gut and the brain. In the mouse brain, 5 μm MP exposure significantly depleted serotonin levels, whereas both MNP sizes induced a compensatory elevation in SOD activity and substantial dysregulation of pro-inflammatory cytokines. Notably, these biochemical alterations occurred without a distinct corresponding shift in behavioral or histopathological profiles. Our results also highlighted that exposure frequency may be a key determinant of MNP-induced toxicity, suggesting a potential need for risk assessment of MNP in humans.