Zearalenone (ZEN) impairs motor function and induces neurotoxicity via inflammatory pathways: Evidence from zebrafish models and molecular docking studies.

ZEN is a low-molecular-weight food contaminant that is frequently detected in various crops and regions due to its high thermal stability and persistence. It poses a significant threat to the biological nervous system. However, the molecular mechanisms underlying ZEN-induced neurotoxicity remain incompletely understood. To further explore this issue, this study focused on the effects of ZEN on the nervous system, particularly its key targets and related molecular mechanisms. The study combined network toxicology and molecular docking methods and performed behavioral analysis of zebrafish larvae exposed to ZEN. Firstly, motor capacity tests revealed that ZEN exposure significantly reduced the overall movement speed of zebrafish larvae during both photoperiod and dark cycles. We then identified 141 potential targets associated with ZEN-induced neurotoxicity from the GeneCards, OMIM, and DrugBank databases. Further screening using STRING and Cytoscape software extracted 25 key nodes, including TP53, AKT1, CASP3, MAPK3, and NFKB1. Analysis of GO and KEGG pathways suggested 20 of the most relevant signaling pathways and indicated that the core targets of ZEN-induced neurotoxicity were primarily involved in inflammatory pathways. Molecular docking using AutoDock further confirmed the strong binding affinity between ZEN and the targets. All six core target proteins exhibited strong binding affinity with ZEN, with binding energies of less than -7. In summary, the results of this study suggest that ZEN may impact cognitive dysfunction and neuropathy by activating neuroinflammatory signaling pathways, ultimately leading to neuronal death. This study provides important insights into the molecular mechanisms of ZEN-induced neurotoxicity and highlights the potential for prevention and treatment of diseases associated with exposure to ZEN and similar food contaminants.