Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Campus, Richmond, VA 23298, USA.
J Neuroinflammation. 2011 Aug 24;8:105. doi: 10.1186/1742-2094-8-105.
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.
越来越多的证据表明，各种形式的空气污染与人类和动物模型中的神经炎症和神经病理学有关，但对长期暴露的影响知之甚少。
我们探讨了亚慢性接触柴油机尾气（DE）对中枢神经系统的影响，并探讨了引发神经炎症和早期神经病理学标志物的最低水平。
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 暴露导致所有测试区域的 TNFα 水平升高，除小脑外。中脑区域最为敏感，暴露于低至 100 μg PM/m³ 的 DE 即可显著增加大脑 TNFα 水平。然而，这种对 DE 的敏感性并没有赋予所有神经炎症标志物，因为中脑在所有测试浓度下均未增加 IL-6 表达，仅在高浓度下增加 IL-1β 表达，并且 MIP-1α 表达减少，表明亚慢性暴露可能会发生代偿机制。暴露于 992 μg PM/m³ 的小鼠额叶 Aβ42 水平最高，而在较高的 DE 浓度（992 和 311 μg PM/m³）下，tau[pS199]水平在颞叶和额叶均升高，表明与临床前阿尔茨海默病相关的蛋白质受到影响。α 突触核蛋白水平在中脑对 992 μg PM/m³ 暴露的反应中升高，支持空气污染可能与早期帕金森病样病理学有关。
综上所述，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为敏感。然而，仅在较高暴露水平下，与神经退行性疾病相关的蛋白质升高，表明空气污染引起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。
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