Paraquat-induced neurogenesis abnormalities via Drp1-mediated mitochondrial fission

Neurogenesis is a fundamental process in the development and plasticity of the nervous system, and its regulation is tightly linked to mitochondrial dynamics. Imbalanced mitochondrial dynamics can result in oxidative stress, which has been implicated in various neurological disorders. Paraquat (PQ), a commonly used agricultural chemical known to be neurotoxic, induces oxidative stress that can lead to mitochondrial fragmentation. In this study, we investigated the effects of PQ on neurogenesis in primary murine neural progenitor cells (mNPCs) isolated from neonatal C57BL/6 mice. We treated the mNPCs with 0-40 mu M PQ for 24 h and observed that PQ inhibited their proliferation, migration, and differentiation into neurons in a concentration-dependent manner. Moreover, PQ induced excessive mitochondrial fragmentation and upregulated the expression of Drp-1, p-Drp1, and Fis-1, while downregulating the expression of Mfn2 and Opa1. To confirm our findings, we used Mdivi-1, an inhibitor of mitochondrial fission, which reversed the adverse effects of PQ on neurogenesis, particularly differentiation into neurons and migration of mNPCs. Additionally, we found that Mito-TEMPO, a mitochondriatargeted antioxidant, ameliorated excessive mitochondrial fragmentation caused by PQ. Our study suggests that PQ exposure impairs neurogenesis by inducing excessive mitochondrial fission and abnormal mitochondrial fragmentation via oxidative stress. These findings identify mitochondrial fission as a potential therapeutic target for PQ-induced neurotoxicity. Further research is needed to elucidate the underlying mechanisms of mitochondrial dynamics and neurogenesis in the context of oxidative stress-induced neurological disorders.

Automated summary

Neurogenesis is a vital process in the nervous system development, and it is regulated by mitochondrial dynamics. Imbalanced mitochondrial dynamics caused by oxidative stress have been associated with various neurological disorders. In this study, we examined the effects of PQ, a neurotoxic agricultural chemical, on neurogenesis in primary murine neural progenitor cells. Our results showed that PQ inhibited cell proliferation, migration, and neuronal differentiation in a concentration-dependent manner. PQ induced excessive mitochondrial fragmentation and altered the expression of proteins involved in mitochondrial dynamics. Inhibiting mitochondrial fission and using a mitochondria-targeted antioxidant could mitigate the adverse effects of PQ on neurogenesis. These findings suggest that mitochondrial fission could be a potential therapeutic target for PQ-induced neurotoxicity.