Wu Jie, Hao Ziwen, Wang Ying, Yan Dongying, Meng Jia, Ma Honglin
Department of Occupational and Environmental Health, School of Public Health, Jinzhou Medical University, Jinzhou, Liaoning, PR China.
Department of Occupational and Environmental Health, School of Public Health, Jinzhou Medical University, Jinzhou, Liaoning, PR China.
Food Chem Toxicol. 2023 Feb;172:113561. doi: 10.1016/j.fct.2022.113561. Epub 2022 Dec 22.
Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with developmental neurotoxicity, the mechanism of which remains obscure. The present study aimed to evaluate cognitive deficits and microglia-originated neuroinflammation in the hippocampus of offspring rats exposed to BDE-209 (30 and 100 mg/kg) during perinatal period. Compared to the control, BDE-209-treated rats showed significant longer escape latency and less platform crossings in tests of Morris water maze. Besides obvious hippocampal neuron damage, increased microglial activation and pro-inflammatory markers (CD86, TNFα, and IL-1β), meanwhile, decreased anti-inflammatory molecules (CD206, IL-10, and Arg1) were induced by BDE-209. Furthermore, we investigated the neuroprotection of melatonin against BDE-209 and whether through sirtuin 1 (SIRT1). Consistent with restored SIRT1 activity, enhanced deacetylation of HMGB1 and inhibited cytoplasmic translocation of HMGB1, reduced expression of proteins involved in TLR4-NF-κB pathway and nuclear transfer of phosphorylated-NF-κB p65, and ultimately suppressed microglial activation and improved spatial memory were observed in 10 mg/kg melatonin-pretreated rats, compared with BDE-209-exposed alone. These results demonstrated that melatonin ameliorated BDE-209-caused cognitive impairment partially through shifting microglia polarization towards anti-inflammatory phenotype in a SIRT1-dependent manner, suggesting a potential mechanism for prevention.
多溴二苯醚（PBDEs）是具有发育神经毒性的持久性环境污染物，其作用机制尚不清楚。本研究旨在评估围产期暴露于BDE - 209（30和100毫克/千克）的子代大鼠海马中的认知缺陷和小胶质细胞源性神经炎症。与对照组相比，接受BDE - 209处理的大鼠在莫里斯水迷宫测试中表现出明显更长的逃避潜伏期和更少的平台穿越次数。此外，BDE - 209诱导明显的海马神经元损伤、小胶质细胞活化增加和促炎标志物（CD86、TNFα和IL - 1β），同时抗炎分子（CD206、IL - 10和Arg1）减少。此外，我们研究了褪黑素对BDE - 209的神经保护作用以及是否通过沉默调节蛋白1（SIRT1）发挥作用。与恢复的SIRT1活性一致，观察到在10毫克/千克褪黑素预处理的大鼠中，高迁移率族蛋白B1（HMGB1）的去乙酰化增强、HMGB1的细胞质转位受到抑制、TLR4 - NF - κB通路相关蛋白的表达减少以及磷酸化NF - κB p65的核转位减少，最终小胶质细胞活化受到抑制且空间记忆得到改善，与单独暴露于BDE - 209的大鼠相比。这些结果表明，褪黑素部分通过以SIRT1依赖的方式使小胶质细胞极化转变为抗炎表型来改善BDE - 209引起的认知障碍，提示了一种潜在的预防机制。
