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首页> 外文期刊>Journal of applied toxicology >Differential mRNA expression of neuroimmune markers in the hippocampus of infant mice following toluene exposure during brain developmental period
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Differential mRNA expression of neuroimmune markers in the hippocampus of infant mice following toluene exposure during brain developmental period

机译：甲苯暴露在脑发育时期甲苯暴露后幼儿小鼠海马中神经影响的差分mRNA表达

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ABSTRACT: Toluene, a volatile organic compound with a wide range of industrial applications, can exert neurotoxic and immunotoxic effects. However, the effects of toluene exposure on developmental immunotoxicity in the brain have not yet been characterized. To investigate the susceptible window to toluene exposure during development and the effects of fetal and neonatal toluene exposure on the neuroimmune markers, gestational day (GD) 14 pregnant mice, postnatal day (PND) 2 and PNO 8 male offspring were exposed to filtered air (control; 0 ppm), or 5 or 50 ppm toluene for 6 h per day for five consecutive days. The neuroimmune markers in the hippocampus of PND 21 were examined using a real-time RT-PCR and immunohistochemical analysis. Mice exposed to 50 ppm toluene on PND 2-6 showed significantly increased levels of nerve growth factor (NGF) and tumor necrosis factor (TNF)-a mRNAs. In contrast, NGF and brain-derived neurotrophic factor (BDNF) and proinflammatory cytokines TNF-a, CCL3, NF-kappaB, toll-like receptor (TLR)-4, astrocyte marker glial fibrillary acidic protein (GFAP), and microglia marker ionized calcium binding adapter molecule (Iba)-I mRNAs were increased significantly in mice exposed to 5 ppm toluene on PND 8-12. These results indicate that low-level toluene exposure during the late postnatal period (PND 8-12) might induce neuroinflammatory mediators via TLR4-dependent NF-kB pathway in the hippocampus of PND 21 male mice. Among the three developmental phases, PND 8-12 seems to be most sensitive to toluene exposure. This is the first study to show developmental phase- and dose-specific changes in neuroimmune markers in infant mice following toluene exposure.
机译：摘要：甲苯，一种具有广泛的工业应用的挥发性有机化合物，可以发挥神经毒性和免疫毒性的影响。然而，甲苯暴露对大脑中发育免疫毒性的影响尚未表征。为了在开发过程中探讨易感窗口，胎儿和新生儿甲苯暴露对神经免疫标记物的影响，妊娠期（GD）14孕妇，后期（PND）2和PNO 8雄性后代暴露于过滤空气（连续五天，每天6小时，每天6小时控制; 0 ppm; 0 ppm）。使用实时RT-PCR和免疫组化分析检查PND 21的海马中的神经疫苗标记。暴露于50ppm甲苯的小鼠在PND 2-6上显示出显着增加的神经生长因子（NGF）和肿瘤坏死因子（TNF）-A mRNA。相反，NGF和脑源性神经营养因子（BDNF）和促炎细胞因子TNF-A，CCL3，NF-κB，Toll样受体（TLR）-4，星形胶质细胞标志物胶质纤维酸性蛋白（GFAP）和微胶质标记物离子化在PND 8-12上暴露于5ppm甲苯的小鼠中显着增加钙结合衔接子分子（IBA）-I mRNA。这些结果表明，后期产后期间（PND 8-12）期间低水平的甲苯暴露可能通过PND 21雄性小鼠的海马TLR4依赖性NF-KB途径诱导神经炎性介质。在三个发育阶段中，PND 8-12似乎对甲苯暴露最敏感。这是第一项研究甲苯暴露后婴儿小鼠中神经免疫标记物的发育阶段和剂量特异性变化的研究。

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