Particle Type- and Morphology-Associated Neurotoxicity of Microplastics and Nanoplastics via Divergent PPARγ Modulation in Zebrafish

Fibrous microplastics and nanoplastics (MNPs) dominate many environmental matrices, yet laboratory toxicology largely relies on spherical models. Here, we developed a 405 nm bioimaging strategy enabling autofluorescence-free tracking of spherical polystyrene (PS, 200 nm) and fibrous polyacrylonitrile (PAN, 3-5 μm) in zebrafish larvae. Both particle types accumulated in the head and alimentary tract, but fibrous PAN exhibited preferential retention in the posterior intestine. At matched mass concentrations (200-400 μg/mL), both particles impaired neurodevelopment and locomotor behavior, with fibers inducing more pronounced deficits. Transcriptomic profiling identified PPAR signaling as a shared enriched pathway, yet revealed divergent regulation of pparg: PS downregulated, whereas PAN upregulated its expression. These opposing transcriptional responses were accompanied by contrasting lipid phenotypes and stronger inflammatory responses under fiber exposure. Pharmacological modulation with the well-established PPARγ agonist rosiglitazone differentially altered toxicity, rescuing behavioral deficits in PS-exposed larvae while exacerbating effects in PAN-exposed larvae, consistent with direction-dependent disruption of PPARγ homeostasis. Together, these findings indicate particle type- and morphology-associated neurotoxicity and support integration of these physical properties into environmental hazard evaluation.