Photoaged Nanopolystyrene Affects Neurotransmission to Induce Transgenerational Neurotoxicity in <i>Caenorhabditis elegans</i>

Nanopolystyrene (NPS), a frequently employed nanoplastic, is an emerging environmental contaminant known to cause neurotoxicity in various organisms. However, the potential for transgenerational neurotoxic effects, especially from photoaged NPS (P-NPS), remains underexplored. This study investigated the aging of virgin NPS (V-NPS) under a xenon lamp to simulate natural sunlight exposure, which altered the physicochemical characteristics of the NPS. The parental generation (P0) of <i>Caenorhabditis elegans</i> was exposed to environmental concentrations (0.1-100 μg/L) of V-NPS and P-NPS, with subsequent offspring (F1-F4 generations) cultured under NPS-free conditions. Exposure to 100 μg/L P-NPS resulted in more pronounced deterioration in locomotion behavior in the P0 generation compared to V-NPS; this deterioration persisted into the F1-F2 generations but returned to normal in the F3-F4 generations. Additionally, maternal exposure to P-NPS damaged dopaminergic, glutamatergic, and serotonergic neurons in subsequent generations. Correspondingly, there was a significant decrease in the levels of dopamine, glutamate, and serotonin, associated with reduced expression of neurotransmission-related genes <i>dat-1</i>, <i>eat-4</i>, and <i>tph-1</i> in the P0 and F1-F2 generations. Further analysis showed that the effects of P-NPS on locomotion behavior were absent in subsequent generations of <i>eat-4(ad572)</i>, <i>tph-1(mg280)</i>, and <i>dat-1(ok157)</i> mutants, highlighting the pivotal roles of these genes in mediating P-NPS-induced transgenerational neurotoxicity. These findings emphasize the crucial role of neurotransmission in the transgenerational effects of P-NPS on locomotion behavior, providing new insights into the environmental risks associated with exposure to photoaged nanoplastics.