Integrated study in zebrafish elucidates the pivotal role of ribosomal and metabolic crisis in propiconazole-induced neurotoxicity.

Propiconazole is a widely used triazole fungicide and a pervasive contaminant in aquatic systems. However, its neurotoxic potential and underlying mechanisms remain poorly understood. This study investigated the neurobehavioral effects of propiconazole on adult zebrafish (Danio rerio) at two environmentally realistic concentrations (20 and 180 μg/L) selected to bracket realistic environmental exposure scenarios. A comprehensive analysis combining behavioral tests, transcriptomics, metabolomics, qRT-PCR and Western blotting validation was conducted. Our results demonstrated that propiconazole exposure induced significant, dose-dependent neurobehavioral deficits, including suppressed locomotor activity, diminished exploratory drive, heightened anxiety-like behavior, and impaired spatial learning and memory. Integrated multi-omics analysis revealed a cohesive mechanistic cascade initiating with disruption of the cytoskeleton (actin filament binding) and progressing to severe ribosomal dysfunction, ultimately leading to a crisis in protein synthesis and nucleotide metabolism. The ribosomal function emerged as a central regulatory hub, with the expression of ribosomal genes serving as a key indicator of the transition from adaptive stress response to pathological failure. Concurrently, metabolomic perturbations highlighted deficits in inhibitory neurotransmission (glycine/serine metabolism) and cellular energy homeostasis (purine metabolism). Protein-level validation confirmed the selective dysregulation of ribosomal subunits, revealing an imbalance between the large and small subunits. Our findings delineate a novel mechanistic framework for propiconazole-induced neurotoxicity and propose a tiered biomarker strategy (involving stat1b, rpl23, gstt1a, and glycine) for environmental monitoring and risk assessment.