Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model.
Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model.
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DOI：
10.1371/journal.pone.0253766
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Mack WJ
中科院分区：
文献类型：
--
作者：
Connor M;Lamorie-Foote K;Liu Q;Shkirkova K;Baertsch H;Sioutas C;Morgan TE;Finch CE;Mack WJ
暴露在环境空气污染中与脑白质损伤和神经认知能力下降有关。然而，这种损伤的机制还不是很清楚，在实验模型中仍然很大程度上没有确定其特征。先前的研究表明，暴露在颗粒物(PM)中会导致神经炎症，特别是炎性小胶质细胞的上调。PM是空气污染的一个亚部分。这项研究检查了白质和轴突损伤，并表征了暴露于10周(150小时)PM的小鼠痂体内的小胶质细胞反应性主要由与交通有关的排放组成的纳米颗粒物(≤，空气动力学直径200纳米)是从洛杉矶的一个市区收集的。雄性C57BL/6J小鼠暴露于再雾化NPM或过滤空气中，每天5小时，每周3天，共10周(150小时；n=18)。用免疫组织化学方法检测小胶质细胞中离子钙结合蛋白-1(Iba-1)和诱导型一氧化氮合酶(INOS)的表达，鉴定促炎细胞；用精氨酸酶-1(Arg)免疫组织化学双重染色鉴定抗炎/内稳细胞。用降解性髓鞘碱性蛋白(DMBP)评价髓鞘损伤。用少突胶质细胞转录因子2(Orig2)检测少突胶质细胞计数。用轴突神经丝标志物SMI-312评价轴突损伤程度。暴露于NPM的小鼠的胼胝体中iNOS表达的小胶质细胞较暴露于过滤空气的小鼠显著增加(增加2.2倍；p<；0.05)。与此同时，dMBP免疫荧光密度增加(1.4倍；p<；0.05)，少突胶质细胞数量减少(1.16倍减少；p<；0.05)，神经丝SMI-312减少(1.13倍；p<；0.05)。暴露于NPM可导致成年雄性小鼠痂体内炎性小胶质细胞、白质损伤和轴突降解增加。表达iNOS的小胶质细胞释放细胞因子和活性氧/氮物质，这可能进一步促进了在该模型中观察到的白质损伤。
Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a sub-fraction of air pollution, results in neuroinflammation, specifically the upregulation of inflammatory microglia. This study examines white matter and axonal injury, and characterizes microglial reactivity in the corpus callosum of mice exposed to 10 weeks (150 hours) of PM. Nanoscale particulate matter (nPM, aerodynamic diameter ≤200 nm) consisting primarily of traffic-related emissions was collected from an urban area in Los Angeles. Male C57BL/6J mice were exposed to either re-aerosolized nPM or filtered air for 5 hours/day, 3 days/week, for 10 weeks (150 hours; n = 18/group). Microglia were characterized by immunohistochemical double staining of ionized calcium-binding protein-1 (Iba-1) with inducible nitric oxide synthase (iNOS) to identify pro-inflammatory cells, and Iba-1 with arginase-1 (Arg) to identify anti-inflammatory/ homeostatic cells. Myelin injury was assessed by degraded myelin basic protein (dMBP). Oligodendrocyte cell counts were evaluated by oligodendrocyte transcription factor 2 (Olig2). Axonal injury was assessed by axonal neurofilament marker SMI-312. iNOS-expressing microglia were significantly increased in the corpus callosum of mice exposed to nPM when compared to those exposed to filtered air (2.2 fold increase; p<0.05). This was accompanied by an increase in dMBP (1.4 fold increase; p<0.05) immunofluorescent density, a decrease in oligodendrocyte cell counts (1.16 fold decrease; p<0.05), and a decrease in neurofilament SMI-312 (1.13 fold decrease; p<0.05) immunofluorescent density. Exposure to nPM results in increased inflammatory microglia, white matter injury, and axonal degradation in the corpus callosum of adult male mice. iNOS-expressing microglia release cytokines and reactive oxygen/ nitrogen species which may further contribute to the white matter damage observed in this model.
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影响因子：
6.8
作者：
Cacciottolo M;Wang X;Driscoll I;Woodward N;Saffari A;Reyes J;Serre ML;Vizuete W;Sioutas C;Morgan TE;Gatz M;Chui HC;Shumaker SA;Resnick SM;Espeland MA;Finch CE;Chen JC
通讯作者：
Chen JC
影响因子：
2.5
作者：
Calderon-Garciduenas, Lilian;Engle, Randall;D'Angiulli, Amedeo
通讯作者：
D'Angiulli, Amedeo
影响因子：
9.3
作者：
Cheng H;Davis DA;Hasheminassab S;Sioutas C;Morgan TE;Finch CE
通讯作者：
Finch CE
DOI：
10.1016/j.jstrokecerebrovasdis.2018.01.030
发表时间：
2018-07-01
影响因子：
2.5
作者：
Dominguez, Reymundo;Zitting, Madison;Mack, William J.
通讯作者：
Mack, William J.
影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK