Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Chem Biol Interact. 2020 May 25;323:109076. doi: 10.1016/j.cbi.2020.109076. Epub 2020 Mar 30.
A growing body of evidence indicates that exposure to nonylphenol (NP), a typical persistent organic pollutant (POP), in early life results in the impairment of the central nervous system (CNS), but the underlying mechanism still remains to be elucidated. High levels of pro-inflammatory cytokines in the brain have been implicated in the CNS damages. The animal model of exposure to NP in early life was established by maternal gavage during the pregnancy and lactation in the present study. We found that exposure to NP in early life increased the levels of pro-inflammatory cytokines in the rat prefrontal cortex. Interestingly, the levels of pro-inflammatory cytokines in the intestine as well as in the serum were also increased by NP exposure. Furthermore, the increased permeability of intestinal barrier and blood-brain barrier (BBB), two critical barriers in the gut to brain communication, was observed in the rats exposed to NP in early lives. The decreased expression of zonula occludens-1 (ZO-1) and claudin-1 (CLDN-1), tight junction proteins (TJs) that responsible for maintaining the permeability of intestinal barrier and BBB, was found, which may underlie these increases in permeability. Taken together, these results suggested that the disturbed gut-brain communication may contribute to the increased levels of pro-inflammatory cytokines in the prefrontal cortex caused by NP exposure in early life.
越来越多的证据表明，生命早期接触壬基酚（NP）这种典型的持久性有机污染物（POP）会导致中枢神经系统（CNS）受损，但潜在机制仍有待阐明。大脑中高水平的促炎细胞因子与 CNS 损伤有关。本研究通过在孕期和哺乳期对母体进行灌胃建立了生命早期接触 NP 的动物模型。我们发现，生命早期接触 NP 会增加大鼠前额叶皮层中促炎细胞因子的水平。有趣的是，NP 暴露还会增加肠道和血清中促炎细胞因子的水平。此外，还观察到生命早期接触 NP 的大鼠肠道屏障和血脑屏障（BBB）通透性增加，这两个是肠道到大脑通讯的关键屏障。发现负责维持肠道屏障和 BBB 通透性的紧密连接蛋白（TJ） zonula occludens-1（ZO-1）和 claudin-1（CLDN-1）的表达减少，这可能是通透性增加的基础。综上所述，这些结果表明，肠道-大脑通讯的紊乱可能导致 NP 暴露早期引起前额叶皮层中促炎细胞因子水平升高。
