PUBLICATION
Diesel exhaust extract exposure induces neuronal toxicity by disrupting autophagy
- Authors
- Barnhill, L.M., Khuansuwan, S., Juarez, D., Murata, H., Araujo, J.A., Bronstein, J.M.
- ID
- ZDB-PUB-200422-142
- Date
- 2020
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 176(1): 193-202 (Journal)
- Registered Authors
- Barnhill, Lisa, Bronstein, Jeff, Khuansuwan, Sataree
- Keywords
- none
- MeSH Terms
-
- Air Pollutants/toxicity*
- Air Pollution
- Autophagy/drug effects*
- Environmental Exposure
- Humans
- Inhalation Exposure
- Neurodegenerative Diseases
- Neurons/drug effects
- Particulate Matter/toxicity
- Plant Extracts
- Vehicle Emissions/toxicity*
- PubMed
- 32298450 Full text @ Toxicol. Sci.
- CTD
- 32298450
Citation
Barnhill, L.M., Khuansuwan, S., Juarez, D., Murata, H., Araujo, J.A., Bronstein, J.M. (2020) Diesel exhaust extract exposure induces neuronal toxicity by disrupting autophagy. Toxicological sciences : an official journal of the Society of Toxicology. 176(1):193-202.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping