Jesus Araujo, M.D., Ph.D.
University of California, Los Angeles
A new NIEHS-funded study uncovered the molecular mechanism by which exposure to diesel exhaust can damage brain cells and lead to behavioral deficits common in neurodegenerative conditions such as Parkinson’s disease.
Using zebrafish, the researchers studied how chemicals in diesel exhaust can alter neurons and influence behavior. They also looked at molecular activity in several pathways in the brain related to Parkinson's disease to understand how the chemicals affected the brain.
Zebrafish treated with diesel exhaust extract showed significantly less movement during light cycles and progressive loss of neurons compared to unexposed fish. In treated fish, the researchers reported fewer autophagosomes, which are molecular pouches that dispose of broken-down proteins in healthy neurons. This led to a toxic buildup of a protein called alpha-synuclein in the brain. Accumulation of alpha-synuclein is commonly seen in Parkinson’s patients. The team saw similar results when they looked at cultured human brain cells exposed to diesel exhaust.
Interestingly, when fish were also treated with nilotinib, a drug that helps cells break down and remove old proteins, diesel exhaust exposure no longer killed neurons. According to the authors, these results explain why long-term exposure to traffic-related air pollution increases neurodegenerative disease risk, and point to opportunities to identify therapies that protect the brain.
Citation: Barnhill LM, Khuansuwan S, Juarez D, Murata H, Araujo JA, Bronstein JM. 2020. Diesel exhaust extract exposure induces neuronal toxicity by disrupting autophagy. Toxicol Sci 176(1):193-202.