ZFIN ID: ZDB-PUB-200422-142
Diesel exhaust extract exposure induces neuronal toxicity by disrupting autophagy
Barnhill, L.M., Khuansuwan, S., Juarez, D., Murata, H., Araujo, J.A., Bronstein, J.M.
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.
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.