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Embryonic exposure to 6:2 fluorotelomer alcohol mediates autism spectrum disorder-like behavior by dysfunctional microbe-gut-brain axis in mice
Journal of Hazardous Materials ( IF 12.2 ) Pub Date : 2024-12-01 , DOI: 10.1016/j.jhazmat.2024.136739
Yunhui Xia, Liehai Hu, Ke Ren, Xiaodong Han, Yun Sun, Dongmei Li

6:2 fluorotelomer alcohol (6:2 FTOH) is considered an emerging contaminant as a substitute for perfluoroalkyl and polyfluoroalkyl substances. Autism spectrum disorder (ASD) is a highly heterogeneous childhood neurodevelopmental disorder, the prevalence of which has been significantly increasing globally, possibly due to rising exposure to environmental pollutants. Additionally, the microbe-gut-brain axis plays a crucial role in the development of ASD. The purpose of study was to investigate the impact of embryonic 6:2 FTOH exposure on neurological development in mice and explore the potential involvement of the microbe-gut-brain. Pregnant mice were orally administered 6:2 FTOH from gestation day 8.5 until delivery, and follow-up testing was performed on day 22 post-delivery. The findings revealed that embryonic exposure to 6:2 FTOH led to ASD-like symptoms, cortical neuron apoptosis, glial cell activation, and abnormal synapse formation in mice. Furthermore, impairment of colonic barrier function, inflammatory response, and dysbiosis in gut microbiota were observed. Interestingly, supplementation with Lactobacillus rhamnosus GG during embryonic development mitigated these adverse outcomes. This study enhances our understanding of how environmental pollutants can impact neurological development in children and provides valuable insights for clinical prevention, diagnosis, and treatment strategies for non-genetic ASD.

中文翻译:


胚胎暴露于 6:2 含氟调聚物醇通过小鼠功能失调的微生物-肠-脑轴介导自闭症谱系障碍样行为



6:2 含氟调聚物醇 (6:2 FTOH) 被认为是一种新兴污染物,可替代全氟烷基和多氟烷基物质。自闭症谱系障碍 (ASD) 是一种高度异质性的儿童神经发育障碍,其患病率在全球范围内显着增加,这可能是由于暴露于环境污染物的增加。此外,微生物-肠道-大脑轴在 ASD 的发展中起着至关重要的作用。研究的目的是调查胚胎 6:2 FTOH 暴露对小鼠神经发育的影响,并探索微生物-肠-脑的潜在参与。妊娠小鼠从妊娠第 8.5 天至分娩时口服 6:2 FTOH,并在分娩后第 22 天进行随访检测。研究结果显示,胚胎暴露于 6:2 FTOH 会导致小鼠出现 ASD 样症状、皮质神经元凋亡、神经胶质细胞活化和突触形成异常。此外,观察到肠道菌群结肠屏障功能受损、炎症反应和菌群失调。有趣的是,在胚胎发育过程中补充鼠李糖乳杆菌 GG 减轻了这些不良结局。这项研究增强了我们对环境污染物如何影响儿童神经发育的理解,并为非遗传性 ASD 的临床预防、诊断和治疗策略提供了有价值的见解。
更新日期:2024-12-01
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