Particle size-dependent neurotoxicity of microplastics in zebrafish (Danio rerio): Spatially resolved lipidomics links metabolic dysregulation to neurological disorders

Microplastics (MPs) are persistent environmental contaminants that pose escalating threats to ecosystem integrity and human health. However, spatial alterations in lipid metabolism following MP exposure remain poorly characterized. To elucidate the molecular mechanisms underlying MP toxicity, lipidomics coupled with Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was employed to visualize polypropylene microplastics (PP-MPs) induced molecular disruptions in zebrafish. Lipid dysregulation was predominantly localized to muscle, intestinal and brain tissues. Changes in the spatial distribution of lipids were associated with MP ingestion, and specific molecular ions indicative of MP toxicity were identified. Region-specific perturbations in polyunsaturated fatty acids, phospholipids, sulfatides, triacylglycerols, and bile acid intermediates were concurrently visualized for the first time. The results demonstrated that PP-MPs, particularly smaller particles, induced inflammation, disrupted glycerophospholipid metabolism, and caused neurological damage. By correlating spatial lipid profiles with phenotypic outcomes, this study could provide novel insights into the mechanistic link between MP exposure and lipid metabolic disturbances, thereby informing ecological risk assessments.