Proteome profiling of emamectin-treated primary rat cortical cells following up to twelve days in vitro exposure

This study identifies altered proteomic pathways that may be involved in mechanistic pathways for neurotoxicity (NT) and developmental neurotoxicity (DNT), using primary rat cortical cultures. Emamectin benzoate (EMB) insecticide was chosen as a test chemical. To compare the proteomic expression data to previously described effects related to Neurite Outgrowth (NOG) and alterations in cortical cell culture multielectrode array electrical activity produced by EMB, data was retrieved from the CompTox Chemicals Dashboard. In the current acute EMB experiments, starting the exposure at DIV7 for up to 24 h. 241 proteins were significantly changed at a high EMB dose. However, only two proteins demonstrated significant protein abundance change at all three EMB concentrations at 24 h after treatment. In the developmental paradigm involving continuous EMB treatment from 2 h after plating to collection day, the largest number of significant protein ratios (104) were recorded for the longest treatment duration and highest concentration, 1.25 μM, day in vitro 12 (DIV12), where 85 proteins were downregulated and 20 proteins were upregulated. Major protein alterations were detected in neurological development and neurite outgrowth, neuronal processes involving GABA and glutamate, microtubules, mitochondria - oxidative phosphorylation, and in the calcium management pathways. The data show that a proteomic-based approach might facilitate understanding of how toxins can initiate neurotoxicity and physiological effects and can possibly be used to propose AOP pathways as models for future screening and prioritizing large number of chemicals for NT/DNT.