Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, Japan.
PLoS One. 2013 Aug 5;8(8):e70145. doi: 10.1371/journal.pone.0070145. Print 2013.
There is an emerging concern that particulate air pollution increases the risk of cranial nerve disease onset. Small nanoparticles, mainly derived from diesel exhaust particles reach the olfactory bulb by their nasal depositions. It has been reported that diesel exhaust inhalation causes inflammation of the olfactory bulb and other brain regions. However, these toxicological studies have not evaluated animal rearing environment. We hypothesized that rearing environment can change mice phenotypes and thus might alter toxicological study results. In this study, we exposed mice to diesel exhaust inhalation at 90 µg/m(3), 8 hours/day, for 28 consecutive days after rearing in a standard cage or environmental enrichment conditions. Microarray analysis found that expression levels of 112 genes were changed by diesel exhaust inhalation. Functional analysis using Gene Ontology revealed that the dysregulated genes were involved in inflammation and immune response. This result was supported by pathway analysis. Quantitative RT-PCR analysis confirmed 10 genes. Interestingly, background gene expression of the olfactory bulb of mice reared in a standard cage environment was changed by diesel exhaust inhalation, whereas there was no significant effect of diesel exhaust exposure on gene expression levels of mice reared with environmental enrichment. The results indicate for the first time that the effect of diesel exhaust exposure on gene expression of the olfactory bulb was influenced by rearing environment. Rearing environment, such as environmental enrichment, may be an important contributive factor to causation in evaluating still undefined toxic environmental substances such as diesel exhaust.
人们日益关注到,颗粒物空气污染会增加脑神经疾病发病的风险。小的纳米颗粒主要来源于柴油废气颗粒,通过鼻腔沉积到达嗅球。据报道,柴油废气吸入会引起嗅球和其他脑区的炎症。然而,这些毒理学研究并没有评估动物的饲养环境。我们假设饲养环境可以改变动物的表型,从而可能改变毒理学研究结果。在这项研究中,我们将小鼠在标准笼或环境丰富条件下饲养 28 天后,每天暴露于 90μg/m(3)的柴油废气中 8 小时。微阵列分析发现 112 个基因的表达水平发生了变化。使用基因本体论进行功能分析表明,失调的基因参与了炎症和免疫反应。通路分析支持这一结果。定量 RT-PCR 分析证实了 10 个基因。有趣的是,在标准笼环境中饲养的小鼠嗅球的背景基因表达受到了柴油废气吸入的影响,而在环境丰富条件下饲养的小鼠,柴油废气暴露对其基因表达水平没有显著影响。这些结果首次表明,饲养环境会影响嗅球中柴油废气暴露对基因表达的影响。饲养环境(如环境丰富)可能是评估仍未明确的有毒环境物质(如柴油废气)的致病因素的一个重要贡献因素。