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Particle Type- and Morphology-Associated Neurotoxicity of Microplastics and Nanoplastics via Divergent PPARγ Modulation in Zebrafish
Summary
Scientists exposed young zebrafish to two common types of plastic pollution, tiny round beads and tiny fibers, and found both harmed brain development and movement, but the fiber-shaped particles caused worse effects and got stuck in the gut longer. The two shapes even disrupted a key metabolism-related gene in opposite ways, meaning a drug that helped fix damage from round particles actually made things worse for fiber exposure. This suggests that not all microplastics are equally risky, and their shape, not just their chemical makeup, matters for understanding how they might affect health.
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.