Citation:

Valdez, M., D. Freeborn, A. Johnstone, A. Tennant, AND P. Kodavanti. The Impact of Ozone Exposure and Sedentary Lifestyle on Microglia and Mitochondrial Bioenergetics of Female Long-Evans Rats. Society for Toxicology Meeting, Baltimore, Maryland, March 10 - 14, 2019.

Impact/Purpose:

This presentation is about the interaction of chemical stressors (ozone; an air pollutant) with non-chemical factors such as active lifestyle. The work was conducted under the Safe and Healthy Communities (SHC) project to try to understand the mechanisms responsible for these interactive effects. This information could be used by the program offices and regions to understand if nonchemical factors influence the toxicity of chemical factors.

Description:

Ozone is a widespread and highly reactive air pollutant that produces cardiovascular and pulmonary dysfunction. We sought to assess neurological changes in glial morphology and mitochondrial bioenergetics in response to both sedentary lifestyle and ozone (O3) exposure. Astrocytes work intimately with neurons to sustain functioning synapses as well as preserve the blood brain barrier. Microglia are highly plastic and aid in safeguarding the brain by removing damaged neurons, plaques, and xenobiotics. Mitochondria are key regulators of cellular energy homeostasis and may play a role in mechanisms of neurodegenerative disorders and chemically induced neurotoxicity. We developed an animal model in which female Long-Evans rats were either sedentary or active (exercise on running wheels) starting at postnatal day (PND) 22 until the age of PND 100 and then exposed to O3 (0, 0.25, 0.5 or 1.0 ppm) 5 h/day for two consecutive days. Immediately following O3 exposure, the rats were sacrificed and brains were either fixed and stored at 4oC or dissected on ice, quick frozen on dry ice, and stored at -80oC until analysis. For astrocytes (GFAP) and microglia (Iba1) immunohistochemistry, we measured the area of coverage and reactive morphology, respectively, in the hypothalamus (HYP) and hippocampus (HIP), two brain regions with known roles in coordinating stress responses. We found more reactive microglia within the hippocampus in both sedentary and active animals exposed to O3. We next analyzed mitochondrial bioenergetic parameters (complex I, complex II and complex IV) in these brain regions, and the frontal cortex (FC) and cerebellum (CER). Exercise decreased complex I enzyme (NADH dehydrogenase) activity in hypothalamus and increased it in the cerebellum. Complex II enzyme (succinate dehydrogenase) activity was decreased by both exercise and O3 exposure in the hippocampus. Complex IV enzyme (cytochrome c oxidase) activity was decreased by an interaction of exercise and O3 exposure in the frontal cortex. These results demonstrate that O3 increases microglia reactivity and altered mitochondrial complex II activity within the HIP. (This abstract does not necessarily reflect USEPA policy)

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