Paraquat (PQ) is one of the most widely used herbicides in the world.Although available evidence indicates that people exposed to PQ could increase the risk of developing Parkinson's disease (PD) by selectively impairing dopaminergic neurons, adverse effects of PQ on neural progenitor cells have not been investigated yet.Accumulating evidence indicated that the Wnt/β-catenin signaling and autophagy pathways play important roles during neurodevelopment.However, whether Wnt/GSK-3β/mTOR crosstalk contributes to paraquat-induced neurotoxicity remains unclear.In this study, the in vitro effect of PQ on mouse neural progenitor cells (mNPCs) by treating them with various concentrations of PQ (0, 40, 80, 120μM) for 24 h.We show that PQ treatment reduces the cell viability and induces reactive oxygen species (ROS) prodUction, G1 phase arrest and apoptosis in a dose-dependent manner.To illustrate the underlying molecular mechanism, we examined the mRNA expression of Wnt pathway key genes including Fzdl, Dv12 and β-catenin, autophage pathway key genes including mTOR, mTORC, Atg5, Beclinl, as well as downstream genes including apoptosis genes(Bcl-2 and Bax)and cyclin gene(Cyclin D1).We observed that expression of Fzdl, Dvl2, β-catenin, mTOR, mTORC, Bcl-2, and CyclinD1 mRNA were significantly down-regulated and expression of Atg5, Beclinland Bax mRNA were significantly up-regulated by treating mNPCs with 80 μ M PQ.While Fzdl, Dvl2, β-catenin,mTOR, mTORC, Bcl-2, and CyclinD1 genes expression in the PQ+wntla-treated groups were markedly higher than that of 80 μ M PQ-treated group, and in contrast, Atg5, Beclin1and Bax mRNA expression were lower.Moreover, the number of autophagic vacuoles in the PQ+wnt1a-treated groups was milder than the PQ group.It suggested that PQ can disturb Wnt pathway to regulate downstream gene expression, resulting in mNPCs cell cycle arrest and apoptosis.On the other hand, our results suggested that wnt1a treatment significantly ameliorated paraquat-induced autophagy and apoptosis by the activation of Wnt signaling pathway in mNPCs.
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