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Pre-existent stress increases susceptibility to ozone and wildfire smoke exposure

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  • Overview
Current climate scenarios predict more frequent and longer-lasting heatwaves alongside rise in ambient ozone and particulate levels from widespread wildfires. These conditions are predicted to exacerbate mental health crises and chronic metabolic and immune disorders, especially in vulnerable individuals. We hypothesized that male Wistar-Kyoto (WKY) rats subjected to chronic variable stress, social isolation, or high temperature housing would be susceptible to metabolic effects from exposure to ozone or eucalyptus wildfire smoke. U.S. EPA Institutional Animal Care and Use Committee approved protocols prior to experiments. Initially, we exposed 5-week-old rats to variable stress paradigm or social isolation for 8 weeks and examined stressor interaction with subsequent ozone exposure. As previously demonstrated, ozone (0.8 ppm, 4 hours) increased urinary/plasma corticosterone/epinephrine and depleted pituitary and gonadal hormones. In addition, ozone increased markers of injury/inflammation (e.g. BALF markers, IL-6/Tnf-α). Interestingly, social isolation exacerbated ozone-induced effects and independently caused systemic inflammation that was exacerbated by ozone. Ozone increased glucose, cholesterol, branched chain amino acids, and social isolation exacerbated these effects. Metabolomic analysis revealed ozone-induced changes in lipid metabolism, whereas social isolation changed markers of sphingolipid metabolism linked with neurotransmitter functions and psychiatric disorders like depression. However, ozone-induced changes in selected metabolites of lipid processing were dampened in socially isolated animals when compared to pair-housed animals. In a follow-up study, male rats (4-week-old) housed at ~31 °C had a substantial reduction in body weight gain and increased lean mass compared to 22 °C housed rats. These animals, when exposed to wildfire smoke (~7 mg/m3 x 1hr), showed metabolic changes comparable to ozone-exposed animals (e.g. glucose intolerance). These data demonstrate that prior stresses increase susceptibility to neuroendocrine and metabolic effects of acute air pollution exposure, and that underlying stress likely exacerbates brain and systemic health conditions in individuals exposed to changing climatic conditions. (Does not reflect US EPA policy).

Impact/Purpose

Current climate scenarios predict more frequent and longer-lasting heatwaves alongside rise in ambient ozone and particulate levels from widespread wildfires. These conditions are predicted to exacerbate mental health crises and chronic metabolic and immune disorders, especially in vulnerable individuals.These data demonstrate that prior stresses increase susceptibility to neuroendocrine and metabolic effects of acute air pollution exposure, and that underlying stress likely exacerbates brain and systemic health conditions in individuals exposed to changing climatic conditions.

Citation

Jackson, T., A. Henriquez, S. Snow, D. Alewel, K. Jackson, Mette C. Schladweiler, C. Miller, K. Swift, A. Fisher, S. Vance, S. Gavett, AND U. Kodavanti. Pre-existent stress increases susceptibility to ozone and wildfire smoke exposure. International Particle Toxicology Conference, Santa Fe, NM, August 27 - 31, 2022.
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Last updated on April 04, 2023
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