TDCPP promotes apoptosis and inhibits the calcium signaling pathway in human neural stem cells

Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) is an extensively used organophosphorus flame retardant (OFR). Previous studies have suggested that it has neurotoxic effects, but the neurotoxicity mechanism is still unclear. Neural stem cells are an important in vitro model for studying the neurotoxicity mechanism of pollutants. In this study, we investigated the neurotoxic effects and molecular mechanisms of TDCPP by using human induced pluripotent stem cells (hiPSCs)-derived neural stem cells. We found that TDCPP inhibited the viability of human neural stem cells (hNSCs), stimulated the generation of ROS, arrested the cell cycle in the S phase, and promoted apoptosis. A total of 387 differentially expressed genes were screened out by transcriptome sequencing analysis, and KEGG enrichment analysis showed that the "calcium signaling pathway" was the most significantly enriched. Further studies on the calcium signaling pathway showed that TDCPP disrupted intracellular calcium homeostasis and inhibited the activation of the Ca²⁺/CALM/CaN/CAMK signaling pathway and the expression levels of NFATC2 and GSK3β. In conclusion, TDCPP has significant toxicity on the calcium signaling pathway of human neural stem cells, which may affect the development process of the human nervous system.