Diesel Exhaust Extract Exposure Induces Neuronal Toxicity by Disrupting Autophagy. (16th April 2020)

• Record Type: Journal Article
• Authors: Barnhill, Lisa M; Khuansuwan, Sataree; Juarez, Daniel; Murata, Hiromi; Araujo, Jesus A; Bronstein, Jeff M
• Is Part Of: Toxicological sciences. Volume 176:Number 1(2020)
• Page Start: 193
• Page End: 202
• Publication Date: 2020-04-16
• Subjects: air pollution -- Alzheimer's disease -- autophagy -- diesel exhaust -- dopaminergic neurons -- neurodegeneration -- Parkinson's disease -- synuclein -- ubiquitin proteasome system -- zebrafish; Toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology; Periodicals; 615.9
• DOI: 10.1093/toxsci/kfaa055
• Languages: English
• ISSNs: 1096-6080

Abstract

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.