Neurodevelopmental effects of Cypermethrin in human Neural Stem Cells

Abstract

The lack of adequate models for the study of developmental neurotoxicity has made difficult to correctly assess the risk and effects of toxic exposure. Despite the large body of results on animals, these studies are costly, time consuming and the results are not always reliable to assess the impact of chemical compounds on the developing human brain because animal models do not perfectly reflect human physiology. In vitro systems are becoming a promising tool to assess the toxicological effects of chemical compounds on developmental neurotoxicity with promising results. Currently, stem cells are becoming a useful model to study this type of toxicity. Stem cells are undifferentiated cells with the potential to differentiate into more specialized cell types. They are present during brain development and into adult life, making them a more appropriate model for mimicking key events that take place during embryonic brain development. Cypermethrin (CYP) is one of the most widely used and highly effective synthetic pyrethroids. CYP can enter the body mainly through skin contact but also through inhalation or ingestion of food or water. The main mechanism of action of pyrethroids is the interaction with Na channels and the induction of prolonged depolarization in neurons. In this study, the human neural stem cell line hNS1 was used to evaluate the effects of CYP on early developmental stages. hNS1 cells were exposed to different concentrations of the pesticide and cell death, proliferation and cell fate specification were analyzed under differentiation conditions by immunocytochemistry and RT-qPCR. The results showed that this compound induces apoptotic cell death at the highest doses tested and a decrease in cells in the cell cycle. Besides, CYP causes a decrease in both neurogenesis and gliogenesis in hNS1 cells. In conclusion, CYP has toxic effects on hNS1 cells and should be further studied.