Early life exposure to F-53B induces neurobehavioral changes in developing children and disturbs dopamine-dependent synaptic signaling in weaning mice

作者：Li-Xia Liang, Jingjing Liang, Qing-Qing Li, Mohammed Zeeshan, Zheqing Zhang, Nanxiang Jin, Li‐Zi Lin, Lu-Yin Wu, Ming-Kun Sun, Weihong Tan, Yang Zhou, Chu Chu, Li‐Wen Hu, Ru-Qing Liu, Xiao‐Wen Zeng, Yunjiang Yu, Guang‐Hui Dong · 发表于：Environment International · 年份：2023 · DOI：10.1016/j.envint.2023.108272 · 被引用次数：33 · 研究领域：Immunotoxicology and immune responses、Pesticide Exposure and Toxicity、Mycotoxins in Agriculture and Food

BACKGROUND: Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further investigation. METHODS: Serum F-53B concentrations and Wisconsin Card Sorting Test (WCST) were evaluated in 314 growing children from Guangzhou, China, and the association between them were analyzed. To study the developmental neurotoxicity of F-53B, experiments on sucking mice exposed via placental transfer and breast milk was performed. Maternal mice were orally exposed to 4, 40, and 400 μg/L of F-53B from postnatal day 0 (GD0) to postnatal day 21 (PND 21). Several genes and proteins related to neurodevelopment, dopamine anabolism, and synaptic plasticity were examined by qPCR and western blot, respectively, while dopamine contents were detected by ELISA kit in weaning mice. RESULTS: The result showed that F-53B was positively associated with poor WCST performance. For example, with an interquartile range increase in F-53B, the change with 95 % confidence interval (CI) of correct response (CR), and non-perseverative errors (NPE) was -2.47 (95 % CI: -3.89, -1.05, P = 0.001), 2.78 (95 % CI: 0.79, 4.76, P = 0.007), respectively. Compared with the control group, the highest exposure group of weaning mice had a longer escape latency (35.24 s vs. 51.18 s, P = 0.034) and a lesser distance movement (34.81 % vs. 21.02 %, P < 0.001) in the target quadrant, as observed from morris water maze (MWM) test. The protein e...