Evaluating the Effects of Acute Diesel Exhaust Particle Exposure on P-glycoprotein Function and Expression in the Blood-Brain Barrier

Diesel exhaust particles (DEP) are a major component of air pollution and a source of concern because once inhaled, DEP may reach the brain, contributing to neurodegenerative disorders. One of the blood-brain barrier’s (BBB) main functions is to limit the entry/action of pathogens and xenobiotics like DEP. Specifically, P-glycoprotein (P-gp), a multidrug transporter found in endothelial cells of the BBB, is responsible for the efflux of small molecule drugs and harmful chemicals from the CNS. The goal of this study was to evaluate the effects of acute (24 hr.) DEP exposure on the function and expression of P-gp in the BBB, and in the BBB with microglia in vitro. We used RT-qPCR to measure P-gp expression, immunocytochemistry and fluorescent imaging to qualitatively analyze the presence of P-gp, and a Rhodamine-123 Accumulation Assay to measure the activity of P-gp in the endothelial cells. This work is significant because it is the first to evaluate the effect of DEP on the P-gp of the BBB. The disruption of P-gp and the resulting dysfunction of the BBB may be implicated in air-pollution-related neurodegenerative disorders.