Atrazine induces neurotoxic effects in dopaminergic systems via metabolomic and miRNA alterations

Atrazine (ATR), a globally utilized herbicide, is known to induce neurotoxic effects on the dopaminergic system at high concentrations. While the roles of metabolomics and non-transcriptomics in energy supplementation, reactive oxygen species (ROS) production, and apoptosis are well-documented, their interactions with ATR have not been thoroughly explored. This study investigated the impact of ATR on the dopaminergic system through integrated metabolomic and non-transcriptomic analyses. We observed significant alterations in miRNA expressions that regulate the AMPK and fatty acid metabolism pathways. These disruptions led to abnormal accumulations of L-carnitine and a notable decrease in L-palmitoylcarnitine (L-PC) in the substantia nigra pars compacta (SNpc), impairing mitochondrial β-oxidation and ATP synthesis. Such metabolic disruptions likely contribute to an inadequate energy supply, hastening neuronal degeneration and autophagy. Additionally, changes in the expression of tyrosine hydroxylase and α-synuclein indicated significant damage of ATR exposure to dopaminergic neurons. These results enhance the understanding of ATR's neurotoxic mechanisms and highlight the need for further studies and risk assessments of environmental pollutants that affect the dopaminergic system.