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Combinatory Effects of Various Stress Modalities and Acute Ozone Exposure on Stress Related Gene Expression in the Hippocampus

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  • Overview
Underserved and vulnerable communities are often disproportionally impacted by psychosocial stressors and poor living conditions. These communities are more likely to live in housing near contaminated sites and/or closer to busy roadways. Epidemiological studies have shown that children from disadvantaged communities exposed to various environmental contaminants have increased incidence of asthma and obesity, both morbidities that are also related to increased chronic stress. This study sought to identify how community-level stressors (noise, confinement, fear, and other life stressors) can interact with air pollutants to increase susceptibility to stress. A rat model of chronic stress was developed by exposing rats to unpredicted stressors (restraint, Tilted cage, Shaking, Noise, Predator odor) for a period of 2 months and then tested for its susceptibility to ozone-induced (environmental stressor) gene expression changes in the brain region involved in stress adaption (hippocampus). Another set of rats were single housed during this 8-week period, with no environmental enrichment provide, to model “psychosocial” stress. Rats were exposed to filtered air or ozone (0.8 ppm) for 4h followed immediately by necropsy. We designed a qPCR primer-based array for genes related to glucocorticoid, GABAergic, glutamatergic, and adrenergic signaling as well as stress, neurotrophics and the endocannabinoid system. We found that ozone decreased expression of glucocorticoid receptor genes (nr3c1, nr3c2) independent of stressor. Both stress groups displayed apparent decreases in fkbp4, with no effect of ozone. One of the most profound gene expression changes was found with fkbp5, where ozone dramatically increased expression independent of stress group. Ozone increased gene expression for avp. We found increased expression of Crhr2 only in the no stress group, this effect was blocked in all stress groups. Additionally, ozone decreased expression of bdnf across all groups. These results demonstrate a glucocorticoid mediated signal (nr3c1, nr3c2, fkbp4, fkbp5) in the hippocampus following ozone exposure. (This abstract does not necessarily reflect US EPA policy).

Impact/Purpose

This abstract contains preliminary findings on the combinatory effects of various stress modalities and acute ozone exposure on gene expression in the brain. The focus is on the stress related genes and would like to identify a set of genes modulated by the combined effects of non-chemical and chemical factors. These results will be useful for the agency to make risk assessment decisions on the susceptible populations.

Citation

Valdez, M., D. Freeborn, C. Colonna, U. Kodavanti, AND P. Kodavanti. Combinatory Effects of Various Stress Modalities and Acute Ozone Exposure on Stress Related Gene Expression in the Hippocampus. 59th Annual meeting of Society of Toxicology, Anaheim, CA, March 15 - 19, 2020.
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Last updated on July 24, 2025
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