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Acute Ozone Inhalation Alters Gene Expression and Neuropeptides in Different Brain Regions: Influence of Chronic and Social Stress
Citation:
Freeborn, D., M. Valdez, Prasada Rao Kodavanti, AND U. Kodavanti. Acute Ozone Inhalation Alters Gene Expression and Neuropeptides in Different Brain Regions: Influence of Chronic and Social Stress. Society of Toxicology SOT 2022 - 61st Annual Meeting and ToxExpo, San Diego, California, March 27 - 31, 2022.
Impact/Purpose:
Socioeconomically underserved communities are disproportionally impacted by living in contaminated areas and near roadways with high levels of air pollution. This study seeks to characterize the interrelationships between chemical and non-chemical stressors and their impacts on human health and well-being. This project was designed to identify how community-level stressors (noise, uncomfortable living conditions, confinement, fear, and other life stressors) can interact with air pollutants to increase susceptibility for stress adaptions in the brain via gene expression and neuropeptide changes that regulate the hypothalamic pituitary adrenal (HPA) axis. For this study, a rat model of mild chronic stress was be developed by exposing rats to unpredicted stresses for a period of 2 months and then tested for its susceptibility to ozone-induced (environmental stressor) HPA axis alterations. The proposed goal was to identify key biological mechanisms responsible for exacerbated disease susceptibility in those individuals predisposed to psychosocial stressors, and the social and environmental factors that are responsible for increases in susceptibility. This research will inform as to what factors play a role in health risks. The data obtained from this study will be useful to affected communities across the country.
Description:
Communities disproportionately affected by psychosocial stressors often experience higher levels of pollutant exposures. Air pollutants (e.g., ozone [O3]) have been associated cognitive decline, Alzheimer’s disease, anxiety, and depressive phenotypes. The physiological and biological consequences to the interactive effects of stressors have not been well understood. We hypothesized that mild community level stressors and/or social isolation may interact with air pollutants such as O3 to increase susceptibility, via stress adaptation in the brain involving gene expression and neuropeptide changes that regulate the hypothalamic pituitary adrenal (HPA) axis. In this study, male Wistar-Kyoto (WKY) rats (4 weeks old) were exposed to mild Chronic Stress (CS) (noise, confinement, fear, uncomfortable living conditions), Social stress - isolation (SS), or no stress (NS) for 8 weeks. At 13 weeks of age, they were acutely exposed to air or O3 (0.8 ppm) for 4 hours. Immediately after exposure, brain regions were dissected and snap frozen. RNA from the hippocampus (HIP), bed nucleus of the stria terminalis (BNST), olfactory bulb (OB) and hypothalamus (HYP) was isolated. Gene expression (qPCR) related to glucocorticoid, noradrenergic, neurotrophic, stress, and endocannabinoid signaling was analyzed. Indicators of HPA activation (i.e., corticosterone, blood lymphocyte, and cytokine levels increased with O3 exposure as previously demonstrated. Generally, exaggerated peripheral responses to O3 were detected in the social isolation stress group. Gene expression across all brain regions was altered by O3 exposure as indicated by increased glucocorticoid signaling genes. FKBP5 involved in regulation of glucocorticoid receptor translocation to the nucleus was induced by O3 in all brain regions. The BNST showed the most exaggerated response to O3 in the SS group, indicating an interactive response to multiple stressors. These results indicate that exposure to air pollution (i.e., O3) interacts with community level stressors, especially SS, to modify gene expression and neuropeptide activation. These modifications may underly maladaptive stress responses that increase susceptibility to brain disorders. (This abstract does not necessarily reflect USEPA policy).