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Social Isolation but not Mild Chronic Stress During Early Life Exacerbates Ozone-Induced Metabolic and Immunological Effects in Rats
Citation:
Henriquez, A., S. Snow, Mette C. Schladweiler, C. Miller, AND U. Kodavanti. Social Isolation but not Mild Chronic Stress During Early Life Exacerbates Ozone-Induced Metabolic and Immunological Effects in Rats. Society of Toxicology - Virtual, NA, Virtual, March 14 - 18, 2021.
Impact/Purpose:
We show that psychosocial stressors, especially social isolation affect the neuroendocrine system and induce systemic inflammation in a rodent model. These effects are exacerbated by exposure to ozone, used as a challenge stressor.
Description:
Epidemiological studies have shown that psychosocially stressed individuals have exacerbated responses to air pollution exposure. Our lab and others have recently demonstrated that ozone exposure activates neuroendocrine stress response pathways leading to systemic metabolic and inflammatory responses in rats and humans. The purpose of this study was to identify whether community level stressors (i.e. noise, uncomfortable living conditions, confinement, fear) can interact with ozone to increase susceptibility for immunological and metabolic effects. Male, 4-week-old Wistar-Kyoto rats were randomized into 3 stress groups: No Stress (NS) – control group (i.e. co-housed); Social Isolation (SI) – single-housed; Chronic Stress (CS) – single-housed and subjected to mild unpredicted-randomized stressors (i.e. restraint, tilted cage, shaking, intermittent noise, and predator odor) 5 days/week for 8 weeks. Animals were then exposed acutely to filtered air or ozone (0.8 ppm) as a challenge stressor for 4h followed by necropsy. After 3 weeks of the stress protocol through the end of the study, the CS group had significantly decreased body weight compared to the NS and SI groups. This corresponded with increased adrenal weight and urine corticosterone and metanephrine levels measured in the CS group, suggesting the chronic mild stress protocol was effective. SI and CS depleted circulating luteinizing hormone, prolactin, follicle stimulating hormone, and brain-derived natriuretic factor, but not adrenocorticotrophic hormone in air-exposed rats (SI>CS). SI decreased thyrotropin-releasing hormone while both SI and CS increased corticotropin-releasing hormone. SI also induced more severe systemic inflammation than CS, as evidenced by increases in circulating cytokine levels (i.e. IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, and IFN-γ) regardless of exposure. Ozone exposure led to increases in plasma corticosterone levels (NS and SI), plasma epinephrine (CS), and urine corticosterone and catecholamine metabolites (all groups). Exposure to ozone also led to increases in serum glucose, leptin, and branched-chain amino acids, increases in BALF IL-6 and TNF-α; and decreases in serum thyroid stimulating hormone, prolactin, and luteinizing hormone, with small influence of CS and SI. Systemic inflammation and some pulmonary effects of ozone were exacerbated by SI. Collectively, these data suggest that psychosocial stressors affect the neuroendocrine system and will likely sway the adverse metabolic and inflammatory responses induced by ozone exposure, a challenge stressor. (Does not reflect the US EPA policy).