Recent studies have demonstrated that long-term exposure to fine particulate matter (PM2.5) increases the risk of central nervous (CNS) diseases. As a basic region-leucine zipper (bZip) transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) is essential for protection against chemically induced oxidative stress to restore cellular redox balance. However, the impact of Nrf2 on the neurotoxic effects of PM2.5 remains to understand. In this study, we exposed wild-type (WT) and Nrf2 knockout (Nrf2-/-) mice to 1 mg/kg PM2.5 or deionized water by intranasal instillation for 28 days. After PM2.5 exposure, Nrf2-/- mice exhibited severe nerve injury in olfactory bulb (OB) of mice. In PM2.5-treated OBs, Nrf2 deficiency resulted in lower levels of antioxidant enzymes, greater induction of oxidative stress, microglia activation, inflammation and nuclear factor kappa B (NF-κB) activation compared to the OBs of WT mice. In PM2.5-treated BV2 cells, inhibition of Nrf2 activity significantly decreased cell viability and increased the intracellular reactive oxygen species (ROS) generation and nuclear factor kappa B (NF-κB) phosphorylation. Taken together, our results provide the role Nrf2-reuglated antioxidant and cytoprotective enzymes in protective responses to PM2.5-induced neurotoxicity. Our findings suggest Nrf2-mediated defenses against oxidative stress will help develop new strategies for the prevention and treatment of diseases associated with airborne pollution.
Keywords: Apoptosis; NF-κB; Nrf2; Olfactory bulb; PM(2.5).
Copyright © 2018. Published by Elsevier Inc.