Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, 90048, USA.
Genomics Core, Cedars-Sinai Medical Center, Los Angeles, 90048, USA.
Sci Rep. 2018 Apr 9;8(1):5708. doi: 10.1038/s41598-018-23885-3.
Air pollution is linked to brain inflammation, which accelerates tumorigenesis and neurodegeneration. The molecular mechanisms that connect air pollution with brain pathology are largely unknown but seem to depend on the chemical composition of airborne particulate matter (PM). We sourced ambient PM from Riverside, California, and selectively exposed rats to coarse (PM: 2.5-10 µm), fine (PM: <2.5 µm), or ultrafine particles (UFPM: <0.15 µm). We characterized each PM type via atomic emission spectroscopy and detected nickel, cobalt and zinc within them. We then exposed rats separately to each PM type for short (2 weeks), intermediate (1-3 months) and long durations (1 year). All three metals accumulated in rat brains during intermediate-length PM exposures. Via RNAseq analysis we then determined that intermediate-length PM exposures triggered the expression of the early growth response gene 2 (EGR2), genes encoding inflammatory cytokine pathways (IL13-Rα1 and IL-16) and the oncogene RAC1. Gene upregulation occurred only in brains of rats exposed to PM and correlated with cerebral nickel accumulation. We hypothesize that the expression of inflammation and oncogenesis-related genes is triggered by the combinatorial exposure to certain metals and toxins in Los Angeles Basin PM.
空气污染与脑炎症有关，而脑炎症会加速肿瘤形成和神经退行性病变。将空气污染与脑部病理联系起来的分子机制在很大程度上尚不清楚，但似乎取决于空气中颗粒物（PM）的化学成分。我们从加利福尼亚州里弗赛德采集了环境 PM，并选择性地使大鼠暴露于粗颗粒物（PM：2.5-10μm）、细颗粒物（PM：<2.5μm）或超细颗粒物（UFPM：<0.15μm）中。我们通过原子发射光谱法对每种 PM 类型进行了表征，并在其中检测到镍、钴和锌。然后，我们分别将大鼠暴露于每种 PM 类型中，暴露时间分别为短（2 周）、中（1-3 个月）和长（1 年）。在中间长度的 PM 暴露期间，这三种金属都在大鼠大脑中积累。通过 RNAseq 分析，我们确定中间长度的 PM 暴露会触发早期生长反应基因 2（EGR2）、炎症细胞因子途径（IL13-Rα1 和 IL-16）和致癌基因 RAC1 的表达。基因上调仅发生在暴露于 PM 的大鼠的大脑中，并且与大脑中的镍积累相关。我们假设，炎症和致癌基因相关基因的表达是由洛杉矶盆地 PM 中某些金属和毒素的组合暴露所引发的。
