Conner Kennedy


Dr. Amie K. Lund
Research Topic: 
Air Pollution-Mediated Alterations in CYP Enzyme Expression
Inhalation exposure to traffic-generated air pollutants has been reported to have deleterious effects on the central nervous system (CNS), including blood-brain barrier (BBB) disruption and neurovascular, neuroinflammatory, and neurodegenerative diseases. Cytochrome P450 enzymes (CYPs) are one of the main classes of biotransforming enzymes present in the body, which mediate reactions of thousands of endogenous and exogenous substrates. Altered expression of certain CYP enzymes are associated with neurodegenerative disorders, thus we chose to investigate the effects of inhaled traffic-generated air pollutants on the expression of these enzymes in the CNS on the blood-brain barrier (BBB). Young (2 mo) or aged (18 mo) male C57Bl/6 wild-type mice were placed on either a “Western” high fat (21% fat by content) or low-fat diet, and subsequently exposed to either 300 μg/m 3 of mixed exhaust (MVE: 250 μg/m 3 PM diesel engine + 50 μg/m 3 PM gasoline engine emissions) or filtered air (FA, controls) for 6 hr/day, 7 days/wk, for 50 days. Brain tissue was collected at the end of the exposure period, and prepared for either real-time RT-qPCR or double immunofluorescence, to detect variation in CYP enzyme expression in the cerebrum and/or (BBB). MVE-exposure resulted in significant increases in CYP2D (~1.5-fold), CYP2E1 (~2-fold) enzymes, with trending increases in CYP1B1 enzyme expression in the CNS of aged mice on a low fat diet, while the expression of these same enzymes had the opposite trends in expression (decreased with MVE exposure) in the CNS of young C57Bl/6 mice on a low-fat diet. In the high-fat fed C57Bl/6 mice, we observed a significant decrease in CYP1B1, with trending decreases in CYP2D, CYP2E1, and CYP3A1 mRNA in the aged mice. Inverse (increasing) trends in expression in CYP2D, CYP2E1, and CYP3A1 were observed in the young mice on a high-fat diet, compared to FA controls. Thus, our preliminary findings suggest that inhalation exposure to traffic-generated polluta
Alma Mater: 
B.S. Biochemistry | University of North Texas 2019