The effects of ozone exposure and sedentary lifestyle on neuronal microglia and mitochondrial bioenergetics of female Long-Evans rats

Ozone (O-3) is a widespread air pollutant that produces cardiovascular and pulmonary dysfunction possibly mediated by activation of central stress centers. Epidemiological data suggest that sedentary lifestyles may exacerbate responses to air pollutants such as O-3. We sought to assess neurological changes in response to O-3 exposure and an active lifestyle. We developed an animal model in which female Long-Evans rats were either sedentary or active with continuous access to running wheels starting at postnatal day (PND) 22 until the age of PND 100 and then exposed to O-3 (0, 0.25, 0.5 or 1.0 ppm) 5 h/day for two consecutive days. We found significantly more reactive microglia within the hippocampus (HIP) in animals exposed to O-3 in both sedentary and active rats. No changes were detected in astrocytic coverage. We next analyzed mitochondrial bioenergetic parameters (complex I, complex II and complex IV). Complex I activity was significantly affected by exercise in hypothalamus (HYP). Complex II activity was significantly affected by both exercise and O-3 exposure in the HIP. Concomitant with the changes in enzymatic activity, there were also effects on expression of genes related to mitochondrial bioenergetics and antioxidant production. These results demonstrate that O-3 induces microglia reactivity within stress centers of the brain and that mitochondrial bioenergetics are altered. Some of these effects may be augmented by exercise, suggesting a role for lifestyle in O-3 effects on brain mitochondrial bioenergetics parameters in agreement with our previous reports on other endpoints.