Neurotoxicity of traffic-related air pollution
Introduction
Air pollution is a mixture of several components, including gases, organic compounds, metals, and ambient particulate matter (PM); the latter is believed to be the most widespread threat, and has been heavily implicated in disease (Moller et al., 2010, Costa et al., 2014a). PM is usually characterized by aerodynamic diameter: for example, PM10 is comprised of particles <10 μm in diameter, while PM2.5 represents particles <2.5 μm in diameter. Also of relevance are ultrafine PM (UFPM, with diameter <100 nM), which may easily reach the general circulation and distribute to various organs including the brain (Oberdoerster et al., 2002, Genc et al., 2012). UFPM can also access the brain through the nasal olfactory mucosa, reaching first the olfactory bulb (Oberdoerster et al., 2002, Peters et al., 2006). The populations of many countries, particularly in South and East Asia, are often exposed to relatively high levels of PM (≥100 μg/m3) (Brook et al., 2010, Van Donkelaar et al., 2015). Table 1 shows (as an illustrative example) the levels of PM2.5 measured on two randomly chosen days in thirteen cities worldwide; in certain cities in India or China, but also in Peru, maximum levels of PM2.5 are often above 100 μg/m3.
Traffic-related air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component (Ghio et al., 2012). DE contains more than 40 toxic air pollutants, and is a major contributor to ambient PM, particularly of fine (PM2.5) and ultrafine PM (USEPA, 2002). DE exposure is often utilized as a measure of traffic-related air pollution. Diesel engines provide power to a wide range of vehicles, heavy equipment, and other machinery utilized in numerous industries, including transportation, construction, agriculture, railroad, maritime, mining and various types of manufacturing operations. Several million workers in the U.S.A. are exposed to diesel exhaust (DE) either occasionally or on a prolonged basis. Such occupational exposures to DE-PM can also be quite high, often exceeding 200–300 μg/m3 in bus garage, construction and dock workers, with miners experiencing the highest exposures (up to 1000 μg/m3) (Pronk et al., 2009).
The association between air pollution, particularly PM, and morbidity and mortality caused by respiratory and cardiovascular diseases is well established (Brook and Rajagopalan, 2007, Gill et al., 2011). Such peripheral toxicities are believed to be caused by oxidative stress and inflammatory processes (Brook et al., 2010, Lodovici and Bigagli, 2011, Anderson et al., 2012). Increased oxidative stress and inflammation have also been shown following exposure of rodents to DE (Weldy et al., 2012, Yin et al., 2013). In the case of DE exposure, a potential increase in lung tumors has also been suggested (Benbrahim-Tallaa et al., 2012).
Section snippets
Neurotoxicity of air pollution: epidemiological and experimental evidence
In recent years evidence has been accumulating from human epidemiological and animal studies, suggesting that air pollution may negatively affect the central nervous system (CNS) and contribute to CNS diseases (Calderon-Garciduenas et al., 2002, Block and Calderon-Garciduenas, 2009, Genc et al., 2012, Block et al., 2012). PM2.5 and UFPM are of much concern in this regard, as these particles can enter the circulation and distribute to various organs, including the brain (Oberdoerster et al., 2002
Acute diesel exhaust exposure in mice: factors affecting neurotoxicity
Our current studies are investigating neurotoxic effects of DE exposure in both adult and developing mice. Adult mice (8 weeks of age) were exposed for 6 h to filtered air (FA) or to 250–300 μg/m3 DE. DE was derived from a Yanmar YDG5500 diesel generator, with load maintained at 75% of rated capacity, using No. 2 undyed, on-highway fuel and Royal Purple Duralec 15W-40 Synthetic crankcase oil. During exposures, DE concentrations were continuously measured and maintained at steady concentrations
Air pollution as a risk factor for neurodevelopmental and neurodegenerative diseases
In addition to gender and genetic background, age is emerging as an important determinant for susceptibility to air pollution neurotoxicity, and there is much interest in the role that traffic-related air pollution may play in the etiology of neurodevelopmental and neurodegenerative diseases.
Conclusions and further studies
While the connection between air pollution and respiratory diseases was straightforward and easy to formulate, effects on the cardiovascular system have later emerged as most relevant (Gill et al., 2011). In the past decade or so, evidence has started to accumulate suggesting that the nervous system may be an important target for air pollution, and particularly for traffic-related air pollution, of which DE is a common surrogate. As pointed out before, there is a strong convergence between
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Acknowledgments
Research by the authors is supported by grants from NIEHS (R01ES22949, P30ES07033, P42ES04696), NICHD (U54HD083091), and by funds from the Department of Environmental and Occupational Health Sciences, University of Washington.
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