Browsing by Author "Kochi, Camila Y. S."
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Item The Effects of Simulated Vehicle Exhaust Exposure on Behavior and Blood Pressure in Male and Female Rats(2020-12) Kochi, Camila Y. S.; Salim, Samina; Banday, Anees Ahmad; Eriksen, Jason; Lutfy, Kabirullah; Rappenglueck, BernhardLong-term exposure to vehicle exhaust pollution is associated with cardiovascular, respiratory and neurological problems. Understanding biological mechanisms responsible for adverse effects of vehicle pollution to human health are critical. Animal studies offer useful insights. Recently, using a simulated vehicle exhaust exposure (SVEE) model we have published that SVEE, by inducing oxidative stress, results in behavioral and cognitive deficits in male rats. SVEE-induced sex-dependent variations in behavior, cognition, and cardiovascular functions were not examined. This is important as behavioral, cognitive and cardiovascular risks vary with gender. Therefore, in this study, male and female rats were subjected to SVEE for 2 weeks (5h/day) in whole body chambers. Our postulation was that, SVEE increases allostatic load (oxidative stress and inflammation), modifying critical signaling cascades, resulting in neurobehavioral deficits and blood pressure changes in a sex-dependent manner. This hypothesis was tested using three specific aims. In AIM 1, we examined if male and female rats would show differential susceptibility to SVEE-induced neurobehavioral deficits. In AIM 2, we assessed the biochemical changes induced by SVEE in male and female rats, and in AIM 3, we determined if SVEE differentially alters blood pressure and related parameters between male and female rats. Results suggest that as compared to control, male but not female SVEE rats developed memory deficits, exhibited anxiety- and depression-like behavior, accompanied with elevated serum corticosterone, oxidative stress, inflammation (CRP and TNF), and declined antioxidant capacity, glutathione, glyoxalase and SOD activities. Similarly, as compared to control, male but not female SVEE rats exhibited low Cu/Zn SOD, Mn SOD, GSR, and PKC expression levels in amygdala but not in the hippocampus. This was accompanied with elevated IL-6 levels and low ERK1/2, CaMKIV, CREB, BDNF and NMDA receptor subunit expression levels. Interestingly, SVEE did not negatively impact blood pressure, heart rate, or glomerular filtration rate in either male or female rats. Together, SVEE increases allostatic load in vulnerable brain regions, causing downregulation of ERK1/2-CREB-BDNF and CaMKIV-CREB-BDNF signaling, which subdues BDNF and NMDA receptor protein levels, thus declining the potential involvement of synaptic plasticity and neurogenesis in male but not female SVEE rats, causing neurobehavioral deficits. Estrogen due to its antioxidant and anti-inflammatory properties maintains BDNF and NMDA receptor levels, offering neurobehavioral protection.