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

Caihong Huang; Yongli Ye; Jian Ji; Peipei Li; Jia-Sheng Wang; Lili Tang; Yahui Gao; Xiulan Sun

doi:10.1016/j.jhazmat.2025.138901

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

J Hazard Mater. 2025 Jun 10:495:138901. doi: 10.1016/j.jhazmat.2025.138901. Online ahead of print.

Authors

Caihong Huang¹, Yongli Ye¹, Jian Ji¹, Peipei Li¹, Jia-Sheng Wang², Lili Tang², Yahui Gao³, Xiulan Sun⁴

Affiliations

¹ School of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi, Jiangsu 214122, China; Key Laboratory of Screening, Prevention, and Control of Food Safety Risks, State Administration for Market Regulation, Wuxi, Jiangsu 214122, China; Yixing Institute of Food and Biotechnology Co., Ltd, Yixing 214200, China.
² Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA.
³ School of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi, Jiangsu 214122, China.
⁴ School of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi, Jiangsu 214122, China; Key Laboratory of Screening, Prevention, and Control of Food Safety Risks, State Administration for Market Regulation, Wuxi, Jiangsu 214122, China; Yixing Institute of Food and Biotechnology Co., Ltd, Yixing 214200, China. Electronic address: sxlzzz@jiangnan.edu.cn.

PMID: 40516467
DOI: 10.1016/j.jhazmat.2025.138901

Abstract

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.

Keywords: Cyclopiazonic acid; Learning and memory; Metabolomics; Neurological damage.