Deoxynivalenol triggers pyroptosis in mouse hippocampal neurons by activating oxidative stress and interfering with neurotransmitter release.

As a prevalent natural pollutant, deoxynivalenol (DON) exhibits high toxicity, affects multiple organs, can penetrate the blood-brain barrier and induce neurotoxicity, thereby threatening food safety. In this study, we investigated the effects of DON on hippocampal neuronal injuries using both in vivo and in vitro models to evaluate its potential risks. Results showed that subchronic exposure of DON exposure (500 ng/mL in cells and 1 mg/kg.bw in mice) increased excessive ROS production, activated the NF-κB pathway, and upregulated NLRP3 and ASC expression levels. Consequently, this triggered Caspase-1 activation, released IL-1β and IL-18, thereby inducing pyroptosis and causing structural damage in hippocampal neurons. Furthermore, DON exposure markedly disrupted cell cycle progression and interfered with the synthesis and release of several neurotransmitters in vivo and in vitro. Correlation analysis between diseases and metabolites indicated that the differential altered neurotransmitters induced by DON exposure exhibited a strong association with Alzheimer's disease. Correlation analysis between diseases and metabolites indicated that the differentially altered neurotransmitters induced by DON exposure were significantly associated with Alzheimer's disease. In conclusion, subchronic exposure to DON triggered pyroptosis in cells through the activation of oxidative stress and interference with neurotransmitter synthesis, resulting in the loss and damage of hippocampal neurons. This research offers novel insights into the relationship between DON exposure and hippocampal immune inflammation.