Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease.
Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease.
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DOI：
10.1186/1742-2094-8-105
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发表时间：
2011-08-24
影响因子：
9.3
通讯作者：
Block ML
中科院分区：
文献类型：
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作者：
Levesque S;Surace MJ;McDonald J;Block ML
越来越多的证据表明，在人类和动物模型中，不同形式的空气污染与神经炎症和神经病理学有关，但长期暴露的影响却知之甚少。我们探讨了亚慢性暴露于柴油机尾气（DE）的中枢神经系统后果，并提出了引发神经炎症和早期神经病理学标志物所需的最低水平。雄性Fischer 344大鼠通过吸入暴露于DE（992、311、100、35和0 μg PM/m3）6个月。DE暴露导致除小脑外所有检测区域的高浓度TNFα水平升高。中脑区域是最敏感的，低至100 μg PM/m3的暴露显著增加脑TNFα水平。然而，并非所有神经炎症标志物均对DE具有这种敏感性，因为中脑在任何检测浓度下均未显示IL-6表达增加，仅在高浓度下IL-1β表达增加，MIP-1α表达减少，支持亚慢性暴露可能发生代偿机制。暴露于992 μg PM/m3的小鼠额叶中的Aβ42水平最高，颞叶和额叶中的tau [pS199]水平在较高DE浓度（992和311 μg PM/m3）下升高，表明与临床前阿尔茨海默病相关的蛋白质受到影响。暴露于992 μg PM/m3时，中脑中的α突触核蛋白水平升高，支持空气污染可能与早期帕金森病样病理学相关。总之，这些数据支持中脑可能对亚慢性空气污染暴露的神经炎症效应更敏感。然而，DE诱导的与神经退行性疾病相关的蛋白质升高仅限于较高的暴露，这表明空气污染诱导的神经炎症可能先于中脑神经退行性疾病的临床前标志物。
Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3) by inhalation over 6 months. DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.
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影响因子：
15.1
作者：
Frank-Cannon TC;Alto LT;McAlpine FE;Tansey MG
通讯作者：
Tansey MG
影响因子：
3.8
作者：
Campen, Matthew J.;Lund, Amie K.;McDonald, Jacob D.
通讯作者：
McDonald, Jacob D.
影响因子：
5.5
作者：
Cheung, Giselle;Kann, Oliver;Kettenmann, Helmut
通讯作者：
Kettenmann, Helmut
影响因子：
15.9
作者：
Block, Michelle L.;Calderon-Garciduenas, Lilian
通讯作者：
Calderon-Garciduenas, Lilian
影响因子：
6.7
作者：
通讯作者：
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