Redox-driven mechanisms link pesticide-induced microglial immunotoxicity to neurobehavioural impairment in an invertebrate ecotoxicological model.

This study aimed to compare the biological consequences of mitochondrial- versus cytoplasmic-driven superoxide dysregulation, with a focus on microglial immunotoxicity and neurobehavioural outcomes. Murine BV-2 microglial cells were exposed to sublethal concentrations of rotenone (ROT) or paraquat (PQT) to assess cytotoxicity, redox imbalance, mitochondrial alterations, oxidative macromolecular damage, inflammatory modulation, and cytomorphological alterations. In parallel, acute toxicity and neurobehavioural responses were evaluated in the invertebrate model Eisenia fetida. Both pesticides reduced microglial viability and induced early increases in intracellular superoxide and nitric oxide levels, followed by oxidative damage. ROT elicited more pronounced mitochondrial alterations and cytotoxicity, whereas PQT promoted a stronger and sustained pro-inflammatory microglial phenotype, characterized by enhanced cytokine release. In vivo, both compounds impaired neurobehavioural responses, with higher lethality following ROT exposure. Mitochondrial- and cytoplasmic-derived superoxide production differentially modulate redox-sensitive neuroinflammatory pathways, converging on functional neurobehavioural impairment.