Effects of air pollution on the nervous system and its possible role in neurodevelopmental and neurodegenerative disorders

Abstract

Recent extensive evidence indicates that air pollution, in addition to causing respiratory and cardiovascular diseases, may also negatively affect the brain and contribute to central nervous system diseases. Air pollution is comprised of ambient particulate matter (PM) of different sizes, gases, organic compounds, and metals. An important contributor to PM is represented by traffic-related air pollution, mostly ascribed to diesel exhaust (DE). Epidemiological and animal studies have shown that exposure to air pollution may be associated with multiple adverse effects on the central nervous system. In addition to a variety of behavioral abnormalities, the most prominent effects caused by air pollution are oxidative stress and neuro-inflammation, which are seen in both humans and animals, and are supported by in vitro studies. Among factors which can affect neurotoxic outcomes, age is considered most relevant. Human and animal studies suggest that air pollution may cause developmental neurotoxicity, and may contribute to the etiology of neurodevelopmental disorders, including autism spectrum disorder. In addition, air pollution exposure has been associated with increased expression of markers of neurodegenerative disease pathologies, such as alpha-synuclein or beta-amyloid, and may thus contribute to the etiopathogenesis of neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease.

Keywords: Air pollution; Alzheimer's disease; Autism; Diesel exhaust; Neuro-inflammation; Neurodegenerative diseases; Neurodevelopmental disorders; Neurotoxicity; Oxidative stress.

Fig. 1.

Possible mechanism for developmental DE exposure-induced cortical disruption. Developmental exposure of mice to DE (250 μg/m³, from GD 1 to PND 21) causes neuroinflammation, as evidenced by elevated levels of IL-6. This in turn activates STAT3 which acts as a transcription factor and up-regulates DNMT1 expression, leading to decreased reelin levels. Known for its critical role in guiding the process of neuronal migration during development, decreased expression of reelin during critical expression periods leads to altered cortical structures (Chang et al., 2019), as observed in ASD (Stoner et al., 2014). The same developmental DE exposure causes significant alterations in all three behavioral domains of ASD (communication, repetitive behavior, social interactions) (Chang et al., 2018). Figure reproduced from Chang et al. (2019) with permission.