The role of MAPK/NF-κB-associated microglial activation in T-2 toxin-induced mouse learning and memory impairment

• Published in: Food and chemical toxicology 2023-04, Vol.174, p.113663-113663, Article 113663
• Main Authors: Li, Na, Yao, Chun-Yan, Diao, Jun, Liu, Xiao-Ling, Tang, En-Jie, Huang, Qing-Song, Zhou, Yu-Meng, Hu, Yue-Gu, Li, Xiu-Kuan, Long, Jin-Yun, Xiao, Hua, Li, Da-Wei, Du, Ning, Li, Ya-Fei, Luo, Peng, Cai, Tong-Jian
• Format: Article
• Language: English
• Subjects: Animals; Gene Expression Regulation; Lipopolysaccharides - pharmacology; MAPK/NF-κB pathway; Mice; Microglia; Neuroinflammation; NF-kappa B - metabolism; Signal Transduction; T-2 toxin; T-2 Toxin - metabolism; Transcriptomics
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2023.113663

T-2 toxin is a mycotoxin with multiple toxic effects and has emerged as an important food pollutant. Microglia play a significant role in the toxicity of various neurotoxins. However, whether they participate in the neurotoxicity of T-2 toxin has not been reported. To clarify this point, an in vivo mouse model of T-2 toxin (4 mg/kg) poisoning was established. The results of Morris water maze and open-field showed that T-2 toxin induced learning and memory impairment and locomotor inhibition. Meanwhile, T-2 toxin induced microglial activation, while inhibiting microglia activation by minocycline (50 mg/kg) suppressed the toxic effect of the T-2 toxin. To further unveil the potential mechanisms involved in T-2 toxin-induced microglial activation, an in vitro model of T-2 toxin (0, 2.5, 5, 10 ng/mL) poisoning was established using BV-2 cells. Transcriptomic sequencing revealed lots of differentially expressed genes related to MAPK/NF-κB pathway. Western blotting results further confirmed that T-2 toxin (5 ng/mL) induced the activation of MAPKs and their downstream NF-κB. Moreover, the addition of inhibitors of NF-κB and MAPKs reversed the microglial activation induced by T-2 toxin. Overall, microglial activation may contribute a considerable role in T-2 toxin-induced behavioral abnormalities, which could be MAPK/NF-κB pathway dependent. •T-2 toxin induced learning and memory impairment and locomotor inhibition.•The behavioral abnormalities were dependent on microglial activation.•MAPK/NF-κB signaling pathway is involved in T-2 toxin-induced microglial activation.