(158b) Unveil Epigenetic Memory Conferring Parkinson’s Disease Risks Arising from Exposure to Environmental Chemicals

Exposures to a variety of environmental chemicals, such as herbicide and organic solvent have been shown to promote the risk of Parkinson’s Disease (PD) based on population studies leading to increased public concerns of utilizing such chemicals in various applications. Atrazine, one of the most commonly used herbicides in the agricultural industry in the United States, is one of those chemicals. About 80 million pounds of atrazine were used in the U.S. every year. Atrazine residuals at a dose above its EPA limit (3 ppb) have been reported to contaminate drinking water sources. Despite many suggested disease connections with exposure to atrazine, how early-life exposure to atrazine can result in disease on-set at a later life remains poorly understood. In this work, we screened and investigated an array of epigenetic changes as potential transmission mechanism that gives rise to disease risk due to atrazine exposure that can persist and aggravate over time. To do that, we used SH-SY5Y cell line as our model neuronal system and exposed these cells to low-dose of atrazine prior to differentiation. Epigenetic assessments were carried out using immuno-staining, live-cell tracking and qPCR along with phenotypical assessments. Our results suggest that exposure to atrazine can cause immediate changes in epigenome after exposure to atrazine. The response is nonlinearly dependent on Atrazine concentrations. The changes in epigenome can persist through the neuronal differentiation and even attenuated for selected modifications. qPCR results provide further insights about underlying epigenetic enzymes involved in the regulation. Further evidence is provided in the changes of epigenetic make-up and expression of PD-related genes, i.e, α-synuclein, in exposed neurons. Our results thus collectively provide a strong evidence-based mechanism accounting for long-term PD risks due to exposure to atrazine.