Neurochemistry and Neuropharmacology
Author: Analia Czerniczyniec | Email: anaczerni@gmail.com
Analia Czerniczyniec1°, Sofia Mucci1°, Mariela Marazita1°, Gustavo Sevlever1°, María Élida Scassa1°, Leonardo Romorini1°
1° Laboratorio de Investigación Aplicada a Neurociencias, Instituto de Neurociencias, Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia (LIAN-INEU, Fleni-CONICET), B1625XAF, Belén de Escobar, Provincia de Buenos Aires, Argentina.
Paraquat (PQ) is one of the most widely used herbicides in the world. The mechanisms mediating PQ neurotoxicity involved reactive oxygen species (ROS) production. In this study, we investigated the in vitro effects of PQ on human induced pluripotent stem cells (hiPSCs)-derived neural stem cells (NSCs) and neurons by treating them with PQ 50 µM for 24 h. We observed that PQ treatment significantly reduces cell viability by 54% and 66% (p<0.001) in NSCs and neurons, respectively. Meanwhile, PQ treatment significantly decreased the percentage of living cells (31%; p<0.001) in neurons. Due to the importance of mitochondrial function in cell viability, we measured different mitochondrial parameters to establish a potential mechanism for different susceptibility. We observed that mitochondrial membrane potential was decreased by 18% (p<0.05) and 51% (p<0.01) in NSCs and neurons after PQ treatment, respectively. Regarding ROS production, PQ increased superoxide anion levels in NSCs (56%; p<0.05) and neurons (79%¸ p<0.001). Also, cardiolipin oxidation (84%; p<0.001) was present in neurons after PQ exposure. Summing up, PQ effects include changes in mitochondrial function, and NSCs appeared less susceptible than neurons to PQ toxicity. Further studies will be conducted to elucidate if mitochondrial dysfunction presented in hiPSCs-derived neurons induces cell death by activating apoptotic signalling pathways.