Protein Modifications and Metabolic Alterations in the Rat Striatum Following Oil Mist Particulate Matter Exposure Revealed via Untargeted Metabolomics and Phosphoproteomics

Prolonged occupational exposure to oil mist particulate matter (OMPM) poses health risks, yet its neurotoxic effects and underlying mechanisms remain poorly understood. Here, OMPM generated from turbine oil commonly used in occupational labor environments was used to expose rats. The rats were divided into the control and OMPM groups. Following 42 days of exposure, a multidimensional assessment was performed using untargeted metabolomics, phosphoproteomics, behavioral testing, hematoxylin-eosin (HE) staining, transmission electron microscopy (TEM), colorimetric assays, enzyme-linked immunosorbent assay, and Western blotting (WB) to evaluate metabolic alterations, protein phosphorylation, and tissue integrity in the striatum. Integrated omics analyses revealed that differentially phosphorylated proteins and metabolites were remarkably enriched in dopaminergic synapse, Parkinson's disease, and amphetamine addiction pathways (FDR < 0.05), with a regulatory axis involving L-tyrosine, tyrosine hydroxylase (TH), and dopamine (DA) identified. OMPM-exposed rats exhibited depression- and anxiety-like behaviors, alongside striatal pathological and ultrastructural damage. Biochemical analyses showed elevated malondialdehyde and reactive oxygen species levels; reduced superoxide dismutase, glutathione, and glutathione peroxidase activities and total antioxidant capacity; increased glutathione disulfide and inducible nitric oxide synthase expression; and decreased DA and L-tyrosine levels. Additionally, proinflammatory mediators (IL-1β, IL-6, TNF-α, MCP-1, and PGD₂) were significantly upregulated in the striatum. WB analysis further confirmed significant reductions in the relative phosphorylation levels of key regulators in dopaminergic and calcium signaling pathways, including CALM3, CaMK2b, GSK-3β, PRKCG, and TH. Collectively, these findings reveal critical molecular and biochemical alterations in the rat striatum following OMPM exposure and provide a mechanistic basis for understanding depression-like behaviors associated with prolonged OMPM exposure in occupational workers.