The Role of Nrf2 on the Cognitive Dysfunction of High-fat Diet Mice Following Lead Exposure

Lead (Pb) exposure can induce the severe deleterious damage on the central nervous system (CNS). High-fat diet also has been suggested that it had some adverse effects on learning and memory, cognitive function, but there is lack of study on Pb and high-fat diet co-exposure on the CNS damage. In this study, the goal was to explore the effect of Pb on the cognitive function of mice with high-fat diet and to investigate whether Nrf2 signaling pathway acts in the cerebral cortex. C57BL/6J mice were randomly divided into control, high-fat diet, Pb (drinking water with 250 mg/L lead acetate), and high-fat diet with Pb (drinking water with 250 mg/L lead acetate) co-exposure groups for 12 weeks. Experiment data showed that learn memory and exploration ability of mice obviously decreased in Pb and high-fat diet, and reactive oxygen species (ROS) increased; then, the protein expressions of Nrf2, heme oxygenase-1, NADP(H):dehydrogenase quinone 1, and superoxide dismutase 2 were lower significantly compared with those in the control group. This study suggested that down-expressed Nrf2 signaling pathway possibly related to the cognitive dysfunction induced by Pb and high-fat diet co-exposure.