Aerobic Exercise Training Effects on NrF2 and the Antioxidant Defense System

Abstract

Nuclear factor erythroid 2 related factor 2 (NrF2), is an essential transcription factor and master regulator of the antioxidant defense system aiding in cellular protection and survival. PURPOSE: To determine the effect of chronic aerobic exercise on NrF2 and antioxidant factors in individual brain regions. METHODS: Male Sprague Dawley rats (n=12-13/group), 6 weeks of age, were exercise trained (ET) or were sedentary controls (SD). The exercised rats ran on a treadmill using a ramped protocol for 5-7 weeks at an intensity equal to ~75% VO2max. Five hours after the final exercise session rats were euthanized and the cortex, hippocampus, and cerebellum brain regions were collected and stored at -80°C until further analysis. NrF2 protein concentration was measured via western blot analysis. Total glutathione (TGSH) and reduced glutathione (GSH) concentration were measured via HPLC. Manganese superoxide dismutase (Mn-SOD) activity was measured using a spectrophotometric assay. All samples were analyzed in duplicate. The significance level was set a-priori at p<0.05 and the results are displayed as the mean ± SEM. RESULTS: Hippocampal NrF2 was significantly elevated with exercise (ET=3.62±0.20 vs. SD=2.28±0.10 arbitrary units), but was significantly reduced in the cortex (ET=3.20±0.24 vs. SD=6.39±0.26 arbitrary units) and cerebellum (ET=2.02±0.11 vs. SD=3.12±0.16 arbitrary units). TGSH and GSH significantly increased in the hippocampus (ET=182.76±4.64 vs. SD=135.54±4.89 umol/mg protein) (ET=178.94±4.59 vs. SD=131.36±4.83 umol/mg protein), respectively, but were unchanged in cortex and cerebellum regions. No significant differences were detected in Mn-SOD with aerobic exercise in any brain region. CONCLUSIONS: NrF2 and antioxidant factors were up-regulated in the hippocampus only with chronic aerobic exercise training compared to sedentary controls. However, other brain regions respond differently to aerobic exercise. This merits notation as the hippocampus is a primary brain region susceptible to neurodegenerative diseases.