Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

Abstract The cardiovascular effects of inhaled particle matter (PM) are responsible for a substantial morbidity and mortality attributed to air pollution. Ultrafine particles, like those in diesel exhaust emissions, are a major source of nanoparticles in urban environments, and it is these particles that have the capacity to induce the most significant health effects. Research has shown that diesel exhaust exposure can have many detrimental effects on the cardiovascular system both acutely and chronically. This review provides an overview of the cardiovascular effects on PM in air pollution, with an emphasis on ultrafine particles in vehicle exhaust. We consider the biological mechanisms underlying these cardiovascular effects of PM and postulate that cardiovascular dysfunction may be implicated in the effects of PM in other organ systems. The employment of multiple strategies to tackle air pollution, and especially ultrafine particles from vehicles, is likely to be accompanied by improvements in cardiovascular health.

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Acute air pollution exposure alters neutrophils in never-smokers and at-risk humans

European Respiratory Journal ◽

10.1183/13993003.01495-2019 ◽

2019 ◽

Vol 55 (4) ◽

pp. 1901495 ◽

Cited By ~ 1

Author(s):

Denise J. Wooding ◽

Min Hyung Ryu ◽

Hang Li ◽

Neil E. Alexis ◽

Olga Pena ◽

...

Keyword(s):

At Risk ◽

Air Pollution ◽

Diesel Exhaust ◽

Neutrophil Function ◽

Diesel Exhaust Exposure ◽

Copd Patients ◽

At Risk Populations ◽

Never Smokers ◽

Pollution Exposure

Outdoor air pollution exposure increases chronic obstructive pulmonary disease (COPD) hospitalisations, and may contribute to COPD development. The mechanisms of harm, and the extent to which at-risk populations are more susceptible are not fully understood. Neutrophils are recruited to the lung following diesel exhaust exposure, a model of traffic-related air pollution (TRAP), but their functional role in this response is unknown. The purpose of this controlled human-exposure crossover study was to assess the effects of acute diesel exhaust exposure on neutrophil function in never-smokers and at-risk populations, with support from additional in vitro studies.18 participants, including never-smokers (n=7), ex-smokers (n=4) and mild–moderate COPD patients (n=7), were exposed to diesel exhaust and filtered air for 2 h on separate occasions, and neutrophil function in blood (0 h and 24 h post-exposure) and bronchoalveolar lavage (24 h post-exposure) was assessed.Compared to filtered air, diesel exhaust exposure reduced the proportion of circulating band cells at 0 h, which was exaggerated in COPD patients. Diesel exhaust exposure increased the amount of neutrophil extracellular traps (NETs) in the lung across participants. COPD patients had increased peripheral neutrophil activation following diesel exhaust exposure. In vitro, suspended diesel exhaust particles increased the amount of NETs measured in isolated neutrophils. We propose NET formation as a possible mechanism through which TRAP exposure affects airway pathophysiology. In addition, COPD patients may be more prone to an activated inflammatory state following exposure.This is the first controlled human TRAP exposure study directly comparing at-risk phenotypes (COPD and ex-smokers) with lower-risk (never-smokers) participants, elucidating the human susceptibility spectrum.

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Diesel Exhaust Extract Exposure Induces Neuronal Toxicity by Disrupting Autophagy

Toxicological Sciences ◽

10.1093/toxsci/kfaa055 ◽

2020 ◽

Vol 176 (1) ◽

pp. 193-202 ◽

Cited By ~ 3

Author(s):

Lisa M Barnhill ◽

Sataree Khuansuwan ◽

Daniel Juarez ◽

Hiromi Murata ◽

Jesus A Araujo ◽

...

Keyword(s):

Air Pollution ◽

Neurodegenerative Disease ◽

Diesel Exhaust ◽

Disease Risk ◽

In Vivo Model ◽

Autophagic Flux ◽

Zebrafish Model ◽

Diesel Exhaust Particulate ◽

Exhaust Particulate

Abstract The vast majority of neurodegenerative disease cannot be attributed to genetic causes alone and as a result, there is significant interest in identifying environmental modifiers of disease risk. Epidemiological studies have supported an association between long-term exposure to air pollutants and disease risk. Here, we investigate the mechanisms by which diesel exhaust, a major component of air pollution, induces neurotoxicity. Using a zebrafish model, we found that exposure to diesel exhaust particulate extract caused behavioral deficits and a significant decrease in neuron number. The neurotoxicity was due, at least in part, to reduced autophagic flux, which is a major pathway implicated in neurodegeneration. This neuron loss occurred alongside an increase in aggregation-prone neuronal protein. Additionally, the neurotoxicity induced by diesel exhaust particulate extract in zebrafish was mitigated by co-treatment with the autophagy-inducing drug nilotinib. This study links environmental exposure to altered proteostasis in an in vivo model system. These results shed light on why long-term exposure to traffic-related air pollution increases neurodegenerative disease risk and open up new avenues for exploring therapies to mitigate environmental exposures and promote neuroprotection.

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Prenatal diesel exhaust exposure disrupts the DNA methylation profile in the brain of mouse offspring

The Journal of Toxicological Sciences ◽

10.2131/jts.40.1 ◽

2015 ◽

Vol 40 (1) ◽

pp. 1-11 ◽

Cited By ~ 17

Author(s):

Ken Tachibana ◽

Kohei Takayanagi ◽

Ayame Akimoto ◽

Kouji Ueda ◽

Yusuke Shinkai ◽

...

Keyword(s):

Dna Methylation ◽

Diesel Exhaust ◽

Methylation Profile ◽

Diesel Exhaust Exposure ◽

Dna Methylation Profile ◽

The Brain

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Maternal immune response and air pollution exposure during pregnancy: insights from the Early Markers for Autism (EMA) study

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-020-09343-0 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Heather E. Volk ◽

Bo Park ◽

Calliope Hollingue ◽

Karen L. Jones ◽

Paul Ashwood ◽

...

Keyword(s):

Air Pollution ◽

Intellectual Disability ◽

Prenatal Screening ◽

Maternal Serum ◽

Serum Samples ◽

Maternal Immune Activation ◽

Early Markers ◽

Air Pollution Exposure ◽

Pollution Exposure ◽

The Relationship

Abstract Background Perinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy. Objectives To assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study. Methods EMA is a population-based, nested case–control study which linked archived maternal serum samples collected during weeks 15–19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency’s Air Quality System data using the maternal residential address reported during the prenatal screening visit. Results Previous month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from − 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurodevelopmental outcome. IL-6 remained associated with ASD with ID even after adjusting for air pollution exposure. Conclusion This study suggests that maternal immune activation is associated with risk for neurodevelopmental disorders. Furthermore, that prenatal air pollution exposure is associated with small, but perhaps biologically relevant, effects on maternal immune system function during pregnancy. Additional studies are needed to better evaluate how prenatal exposure to air pollution affects the trajectory of maternal immune activation during pregnancy, if windows of heightened susceptibility can be identified, and how these factors influence neurodevelopment of the offspring.

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Abstract 803: Diesel Exhaust Inhalation Enhances Thrombus Formation In Man

Circulation ◽

10.1161/circ.116.suppl_16.ii_155-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Andrew J Lucking ◽

Magnus Lundback ◽

Nicholas L Mills ◽

Dana Faratian ◽

Fleming Cassee ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Air Pollution ◽

Platelet Activation ◽

Diesel Exhaust ◽

Intermittent Exercise ◽

Ex Vivo ◽

Thrombus Formation ◽

Ex Vivo Model ◽

Double Blind

Background: Transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction although the mechanism is unclear. The aim of this study was to investigate the effect of diesel exhaust inhalation on thrombus formation in man using an ex vivo model of thrombosis. Methods and Results: In a double-blind randomized cross-over study, 20 healthy volunteers were exposed to diluted diesel exhaust (300 μg/m3) or filtered air during intermittent exercise for 1 or 2 hours. Thrombus formation, coagulation, platelet activation and inflammatory markers were measured at 2 and 6 hours after exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber at low (212 /s) and high (1,690 /s) shear rates with porcine aortic tunica media as the thrombogenic substrate. Specimens were fixed, stained and thrombus area measured using computerized planimetry. Compared to filtered air, diesel exhaust increased thrombus formation in the low and high shear chambers by 24.2% (p<0.001) and 19.1% (p<0.001) respectively. This increased thrombogenicity was seen at two and six hours, and using two different types of diesel exposure. Although there were no effects on coagulation variables, diesel exhaust inhalation increased platelet-neutrophil (6.5% to 9.2%; P<0.05) and platelet-monocyte (21.0% to 25.0%; P<0.05) aggregates 2 hours following exposure. Conclusions: Inhalation of diesel exhaust increases ex vivo thrombus formation and causes platelet activation in man. These findings provide a potential mechanism that links exposure to traffic-derived air pollution with acute atherothrombotic events including acute myocardial infarction.

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Respiratory Filter Reduces the Cardiovascular Effects Associated With Diesel Exhaust Exposure

JACC Heart Failure ◽

10.1016/j.jchf.2015.07.018 ◽

2016 ◽

Vol 4 (1) ◽

pp. 55-64 ◽

Cited By ~ 15

Author(s):

Jefferson L. Vieira ◽

Guilherme V. Guimaraes ◽

Paulo A. de Andre ◽

Fátima D. Cruz ◽

Paulo H. Nascimento Saldiva ◽

...

Keyword(s):

Diesel Exhaust ◽

Cardiovascular Effects ◽

Diesel Exhaust Exposure

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Study on the Dynamic Changes in Synaptic Vesicle-Associated Protein and Axonal Transport Protein Combined with LPS Neuroinflammation Model

ISRN Neurology ◽

10.1155/2013/496079 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Rui Zhang ◽

Ming Zhao ◽

Hai-jie Ji ◽

Yu-he Yuan ◽

Nai-hong Chen

Keyword(s):

Neurodegenerative Disease ◽

Synaptic Vesicle ◽

Axonal Transport ◽

Molecular Mechanism ◽

Transport Protein ◽

Microglia Activation ◽

Time Dependent ◽

Inflammatory Factors ◽

Dynamic Changes ◽

The Brain

Microglia activation is the major component of inflammation that constitutes the characteristic of neurodegenerative disease. A large amount of researches have demonstrated that inflammation involved in the pathogenesis of PD process activated microglia acting on the neurons through the release of a variety of inflammatory factors. However, the molecular mechanism underlying how it does work on neurons is still unclear. Here, we show that intracerebral injections of LPS induced Parkinson’s disease pathology in C57BL/6J mice. Furthermore, study on the dynamic changes in Synaptic vesicle-associated protein and axonal transport Protein in this process. The results indicated that after administration of LPS in the brain, the inflammatory levels of TNF-α and IL-1β both are elevated, and have a time-dependent.

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Brain Syndemics: Cognitive Deficit, Pathways of Interaction, and the Biology of Inequality

Neurology and Neurobiology ◽

10.31487/j.nnb.2021.02.03 ◽

2021 ◽

pp. 1-12

Author(s):

Merrill Singer ◽

Merrill Singer

Keyword(s):

Air Pollution ◽

Social Inequality ◽

Chronic Stress ◽

Cognitive Deficit ◽

Developmental Delays ◽

Neural Mechanisms ◽

Social Discrimination ◽

Behavioural And Emotional Problems ◽

The Brain ◽

Disadvantaged Families

Children born into and raised in disadvantaged families tend to experience poorer health and more developmental delays, lower achievement, and a greater number of behavioural and emotional problems than children from wealthier homes. There is growing evidence that poverty and social inequality leave their imprint on brain structure as well. The brain exhibits considerable plasticity, one expression of which is shaped by the biology of inequality. A specific consequence is cognitive deficit found among children raised in poverty and subject to social discrimination. This paper argues that several pathways impacted by poverty, including chronic stress, malnutrition, exposure to heightened levels of air pollution, and other toxin exposures, syndemically link social inequality to underlying neural mechanisms and to suboptimal brain development and structure. These deficits need not be permanent and are reversible through urgently needed structural, socio-economic intervention.

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