Neurocognitive impairments induced by cyclopiazonic acid exposure in mice: Effects on learning and memory

Cyclopiazonic acid (CPA), an emerging mycotoxin, has been detected in various foods and feeds. CPA is believed to induce depressive symptoms, but its potential toxic effects on the neurobehavior of organisms remain unclear. In this study, the behavioral effects of 5 mg/kg CPA exposure in C57BL/6 J male mice were evaluated using the open field test, novel object recognition, and the Morris water maze test. Additionally, the underlying mechanisms were investigated by measuring CPA and neurotransmitter levels in the hippocampus, along with metabolomic analysis. The results showed that CPA exposure, which can cross the blood-brain barrier, caused learning and memory dysfunction in mice, accompanied by mild structural damage to the brain and disruption of neurotransmitter homeostasis. The relative levels of GABA and 5-HIAA significantly decreased, while the relative levels of Glu, DA, ACH, and NE were markedly elevated. Untargeted metabolomics analysis revealed that CPA significantly downregulated the levels of arginine while markedly upregulating the levels of glutathione, AMP, and (S)-malate. Furthermore, correlation analysis indicated significant positive and negative correlations between hippocampal metabolites and neurotransmitter changes as well as behavioral markers. These findings provide novel insights into CPA-induced neurotoxicity and offer valuable data for assessing the toxicity of emerging toxins.