Pre-differentiation exposure to low-dose of atrazine results in persistent phenotypic changes in human neuronal cell lines

Exposures to organic pesticides, particularly during a developmental window, have been associated with various neurodegenerative diseases later in life. Atrazine (ATZ), one of the most used pesticides U.S., is suspected be increased neurodegeneration life but few studies assessed neurotoxicity ATZ exposure using human neuronal cells. Here, we exposed SH-SY5Y cells 0.3, 3, and 30 ppb prior differentiating them into dopaminergic-like neurons ATZ-free medium mimic exposure. The differentiated exhibit altered neurite outgrowth SNCA pathology depending on treatment doses. Epigenome changes, such as decreases 5mC (for 0.3 only), H3K9me3, H3K27me3 were observed immediately after These alterations persist compensatory manner neurons. Specifically, significant reductions well as, an increase ATZ-exposed differentiation, suggesting substantial chromatin rearrangements Transcriptional changes relevant epigenetic enzymes also quantified found only partially explain epigenome alteration. Our results thus collectively suggest that low-dose differentiation can result long-lasting risks SNCA-related Parkinson’s Disease.