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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

Authors: Scieszka, David; Hunter, Russell; Begay, Jessica; Bitsui, Marsha; Lin, Yan; Galewsky, Joseph; Morishita, Masako; Klaver, Zachary; Wagner, James; Harkema, Jack R; Herbert, Guy; Lucas, Selita; McVeigh, Charlotte; Bolt, Alicia; Bleske, Barry; Canal, Christopher G; Mostovenko, Ekaterina; Ottens, Andrew K; Gu, Haiwei; Campen, Matthew J; Noor, Shahani

Published In Toxicol Sci, (2022 Feb 28)

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.

PubMed ID: 34865172 Exiting the NIEHS site

MeSH Terms: Air Pollutants*/analysis; Air Pollutants*/toxicity; Animals; Endothelial Cells; Mice; Mice, Inbred C57BL; Particulate Matter/analysis; Particulate Matter/toxicity; Smoke/adverse effects; United States; Wildfires*

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