Neurological Outcomes of Joint Exposure to Polystyrene Micro/Nanospheres and Silver Nanoparticles in Zebrafish.

BACKGROUND: Micro/nanoplastics and silver nanoparticles (AgNPs) are emerging environmental contaminants widely detected in aquatic environments. However, previous research has primarily focused on the interactions between micro/nanoplastics and organic substances or heavy metals, whereas the interactions and combined toxic effects of micro/nanoplastics with AgNPs remain unclear. OBJECTIVE: Our study aimed to investigate the effects and mechanisms of coexposure to AgNPs and polystyrene micro/nanospheres (PS M/NPs) on the nervous system, comparing the toxicity of AgNPs alone and in combination with PS M/NPs in larval zebrafish. METHODS: We investigated the dynamics of AgNPs' (5 nm) adsorption onto PS M/NPs (5 μm/100 nm) using inductively coupled plasma-mass spectrometry. Zebrafish larvae were coexposed to PS M/NPs (200 μg/L) and AgNPs (10 μg/L) from 6 h post fertilization (hpf) to 72 hpf to ∼ 120 hpf to evaluate neuroinflammatory effects from multiple perspectives, including developmental abnormalities, oxidative stress, neurobehavioral differences, vascular development, immune responses, differences in gene expression, and differences upon neuroinflammation inhibitor addition. RESULTS: Adsorption experiments showed PS M/NPs could stably adsorb AgNPs, with higher adsorption in smaller particles. Zebrafish larvae exposed to combined PS M/NPs and AgNPs demonstrated neurodevelopmental abnormalities, including developmental malformations, lower levels of locomotor activity, delayed response, and abnormal neuronal development. In addition, exposed zebrafish also exhibited disrupted neurodevelopmental markers, including vascular and apoptotic indicators, and oxidative stress and neuroimmune responses. Quantitative real-time polymerase chain reaction analysis showed differences in gene expression within neurotoxic pathways in PS M/NPs and AgNPs-exposed zebrafish, focusing on key genes in immunity, apoptosis, vascular, and neural development. Furthermore, these neurotoxic effects induced by combined exposure were alleviated following the introduction of the neuroinflammation inhibitor curcumin. DISCUSSION: Our findings demonstrate that polystyrene nanospheres (PSNPs) intensified AgNPs-induced neurotoxicity in larval zebrafish, whereas polystyrene microspheres (PSMPs) had a lesser effect, indicating distinct gene regulation roles when combined with AgNPs. These findings enhance the assessment of environmental risks in settings with coexisting nanomaterials and microplastics, offering important insights for evaluating combined exposure risks. https://doi.org/10.1289/EHP14873.