Translocation of inhaled ultrafine manganese oxide particles to the central nervous system.
Translocation of inhaled ultrafine manganese oxide particles to the central nervous system.
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DOI：
10.1289/ehp.9030
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发表时间：
2006-08
影响因子：
10.4
通讯作者：
Oberdörster G
中科院分区：
文献类型：
--
作者：
Elder A;Gelein R;Silva V;Feikert T;Opanashuk L;Carter J;Potter R;Maynard A;Ito Y;Finkelstein J;Oberdörster G
对猴子鼻内滴注金超细颗粒（UFP; < 100 nm）和大鼠吸入碳UFP的研究表明，沉积在鼻子中的固体UFP沿着嗅神经到达嗅球。为了确定其他固体金属UFP是否发生嗅觉易位并评估潜在的健康影响，我们将大鼠组暴露于氧化锰UFP（30 nm; ~ 500 μg/m3），同时两个鼻孔开放或右鼻孔封闭。我们分析了锰在肺，肝，嗅球，和其他大脑区域，我们进行了基因和蛋白质分析。暴露12天后，两个鼻孔的专利，锰浓度在嗅球增加了3.5倍，而肺锰浓度增加了一倍，纹状体，额叶皮层，小脑也有增加。肺灌洗分析显示没有肺部炎症的迹象，而在暴露11天后发现嗅球肿瘤坏死因子-α mRNA（~ 8倍）和蛋白质（~ 30倍）增加，并且在Mn水平增加的其他脑区中增加程度较低。嗅球中巨噬细胞炎性蛋白-2、胶质细胞酸性蛋白和神经细胞粘附分子mRNA表达也增加。随着右嗅球闭塞2天的曝光，锰积累只在左侧嗅球。Mn氧化物UFP的溶解为每天< 1.5%。我们得出结论，嗅觉神经元通路是有效的易位吸入氧化锰固体UFP中枢神经系统，这可能会导致炎症变化。我们认为，尽管人类和啮齿动物的嗅觉系统之间的差异，这条途径是相关的人类。
Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs; < 100 nm) and in rats with inhaled carbon UFPs suggested that solid UFPs deposited in the nose travel along the olfactory nerve to the olfactory bulb. To determine if olfactory translocation occurs for other solid metal UFPs and assess potential health effects, we exposed groups of rats to manganese (Mn) oxide UFPs (30 nm; ~ 500 μg/m3) with either both nostrils patent or the right nostril occluded. We analyzed Mn in lung, liver, olfactory bulb, and other brain regions, and we performed gene and protein analyses. After 12 days of exposure with both nostrils patent, Mn concentrations in the olfactory bulb increased 3.5-fold, whereas lung Mn concentrations doubled; there were also increases in striatum, frontal cortex, and cerebellum. Lung lavage analysis showed no indications of lung inflammation, whereas increases in olfactory bulb tumor necrosis factor-α mRNA (~ 8-fold) and protein (~ 30-fold) were found after 11 days of exposure and, to a lesser degree, in other brain regions with increased Mn levels. Macrophage inflammatory protein-2, glial fibrillary acidic protein, and neuronal cell adhesion molecule mRNA were also increased in olfactory bulb. With the right nostril occluded for a 2-day exposure, Mn accumulated only in the left olfactory bulb. Solubilization of the Mn oxide UFPs was < 1.5% per day. We conclude that the olfactory neuronal pathway is efficient for translocating inhaled Mn oxide as solid UFPs to the central nervous system and that this can result in inflammatory changes. We suggest that despite differences between human and rodent olfactory systems, this pathway is relevant in humans.