Neuroinflammatory and Neurometabolomic Consequences From Inhaled Wildfire Smoke-Derived Particulate Matter in the Western United States.

Abstract

Utilizing a mobile laboratory located >300 km away from wildfire smoke (WFS) sources, this study examined the systemic immune response profile, with a focus on neuroinflammatory and neurometabolomic consequences, resulting from inhalation exposure to naturally occurring wildfires in California, Arizona, and Washington in 2020. After a 20-day (4 h/day) exposure period in a mobile laboratory stationed in New Mexico, WFS-derived particulate matter (WFPM) inhalation resulted in significant neuroinflammation while immune activity in the peripheral (lung, bone marrow) appeared to be resolved in C57BL/6 mice. Importantly, WFPM exposure increased cerebrovascular endothelial cell activation and expression of adhesion molecules (VCAM-1 and ICAM-1) in addition to increased glial activation and peripheral immune cell infiltration into the brain. Flow cytometry analysis revealed proinflammatory phenotypes of microglia and peripheral immune subsets in the brain of WFPM-exposed mice. Interestingly, endothelial cell neuroimmune activity was differentially associated with levels of PECAM-1 expression, suggesting that subsets of cerebrovascular endothelial cells were transitioning to resolution of inflammation following the 20-day exposure. Neurometabolites related to protection against aging, such as NAD+ and taurine, were decreased by WFPM exposure. Additionally, increased pathological amyloid-beta protein accumulation, a hallmark of neurodegeneration, was observed. Neuroinflammation, together with decreased levels of key neurometabolites, reflect a cluster of outcomes with important implications in priming inflammaging and aging-related neurodegenerative phenotypes.

• Authors: David Scieszka, Russell Hunter, Jessica Begay, Marsha Bitsui, Yan Lin, Joseph Galewsky, Masako Morishita, Zachary Klaver, James Wagner, Jack R Harkema, Guy Herbert, Selita Lucas, Charlotte McVeigh, Alicia Bolt, Barry Bleske, Christopher G Canal, Ekaterina Mostovenko, Andrew K Ottens, Haiwei Gu, Matthew J Campen, Shahani Noor
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 186 Issue 1 Pg. 149-162 (02 28 2022) ISSN: 1096-0929 [Electronic] United States
• PMID: 34865172 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Air Pollutants
• Particulate Matter
• Smoke

Topics

• Air Pollutants (analysis, toxicity)
• Animals
• Endothelial Cells
• Mice
• Mice, Inbred C57BL
• Particulate Matter (analysis, toxicity)
• Smoke (adverse effects)
• United States
• Wildfires