Exposure of particulate matter (PM₁₀) induces neurodevelopmental toxicity in zebrafish embryos

Particulate matter with 10 μm or less in diameter (PM₁₀) exposure is a major threat to health and environment around the world. Even though a number of clinical and experimental studies have focused on the cardiopulmonary effects of PM₁₀, its impact on neurovascular development and the underlying toxicity is relatively less studied. The present study is therefore undertaken to evaluate the potential toxic effects of PM₁₀ on neurodevelopment and the associated gene expression profiles in the zebrafish embryo/larvae. During 2017-2018, PM₁₀ samples (24 h sampling, 180 sampling days) were collected in an urban downtown site of Jinan, Shandong province, China. To delineate the potential toxic effects of PM₁₀ during neurodevelopment, zebrafish embryos/larvae were exposed to different concentrations viz., 25, 50, 100, 200, and 400 μg/mL of PM₁₀ solution for 24-120 h post-fertilization (hpf) and the effects on the mortality, morphology, swimming behavior, electroencephalogram discharges, growth of dopaminergic neurons, neurovasculature development and gene expression profiles of dopaminergic and neurodevelopment-related genes using qRT-PCR were studied. A significant increase in the mortality rate and morphological abnormalities were observed in 200 μg/mL of the PM₁₀ treated group at 120 hpf. High concentrations (≥100 μg/mL) of PM₁₀ exposure reduced locomotor behavior, caused abnormal electroencephalogram discharges, degeneration of dopaminergic neurons, inhibition of neurovascular development, cerebral hemorrhage, and significant changes in the expression pattern of genes involved in dopaminergic pathway and neurodevelopment such as (th1, dat, drd1, drd2a, drd3, drd4b, syn2a, gap43, α1-tubulin, gfap, map2, elavl3, eno2, neurog1, sox2, shha, and mbp). Taken together, all these parameters collectively imply developmental neurotoxicity and dysfunction of the dopaminergic neurons which provides the first evidence of PM₁₀-induced neurodevelopmental toxicity in the zebrafish embryo/larvae.