Neurotoxicity of traffic-related air pollution

Highlights

• Traffic-related air pollution may cause neurotoxicity.

• Traffic-related air pollution may contribute to neurodevelopmental and neurodegenerative disorders.

• Particulate matter (PM) from diesel exhaust can cause oxidative stress and neuroinflammation.

Abstract

The central nervous system is emerging as an important target for adverse health effects of air pollution, where it may contribute to neurodevelopmental and neurodegenerative disorders. Air pollution comprises several components, including particulate matter (PM) and ultrafine particulate matter (UFPM), gases, organic compounds, and metals. An important source of ambient PM and UFPM is represented by traffic-related air pollution, primarily diesel exhaust (DE). Human epidemiological studies and controlled animal studies have shown that exposure to air pollution, and to traffic-related air pollution or DE in particular, may lead to neurotoxicity. In particular, air pollution is emerging as a possible etiological factor in neurodevelopmental (e.g. autism spectrum disorders) and neurodegenerative (e.g. Alzheimer's disease) disorders. The most prominent effects caused by air pollution in both humans and animals are oxidative stress and neuro-inflammation. Studies in mice acutely exposed to DE (250–300 μg/m³ for 6 h) have shown microglia activation, increased lipid peroxidation, and neuro-inflammation in various brain regions, particularly the hippocampus and the olfactory bulb. An impairment of adult neurogenesis was also found. In most cases, the effects of DE were more pronounced in male mice, possibly because of lower antioxidant abilities due to lower expression of paraoxonase 2.

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 PM_2.5 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 PM_2.5 measured on two randomly chosen days in thirteen cities worldwide; in certain cities in India or China, but also in Peru, maximum levels of PM_2.5 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 (PM_2.5) 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).