The Effect of 7,12-dimethylbenz[a]-anthracene (DMBA) on Physical Activity in Female Mice

BACKGROUND: Regular exercise has been shown to reduce the risk of occurrence for certain cancers. In animal models, DMBA is a synthetic carcinogen that has been established as the gold standard for inducing cancerous tumors in rodents. However, it has yet to be established whether DMBA has an effect on voluntary wheel running in mice. If there is an effect, it would confound any experiment which investigates exercise effects on tumor growth. PURPOSE: The overall purpose of this project was to determine if DMBA altered voluntary wheel running in mice. METHODS: All procedures were approved by TAMU IACUC. SENCAR mice breeder pairs (Charles River) and offspring at 3 weeks of age were group housed and randomly assigned to a group receiving the DMBA (n=69) or not receiving the DMBA treatment (n=22). At 4 weeks of age, two running wheels were placed inside the cages and connected to a computer that measured distance and time. The running wheels were mounted to the cage tops of standard rat cages and equipped with a cycling computer (BC8.12, Sigma Sport) to record running distance and duration. The running wheels were plastic and had a 410mm circumference with a solid running surface. From 8 to 14 weeks of age, mice in the DMBA group were gavaged daily with a DMBA dose (20 µg/mouse) dissolved in corn oil. A two way ANOVA was employed to determine the effect of DMBA on activity with factors of time and treatment. RESULTS: DMBA had no effect on the distance (p=0.51) or duration ran (p=0.12), but significantly decreased the speed at which the mice ran (p=0.02). A post-hoc analysis indicated that significant decreases in speed occurred at weeks 12 (35.2 ±9.2 vs. 46.4 ± 14.6; p=0.0002) and 20 (35.4 ±10.3 vs. 46.2 ± 14.1; p\u3c0.0001) of age. CONCLUSION: Our data suggest that DMBA does not affect the distance or time spent running on a wheel, but does affect the speed at which the mice run. While DMBA decreased speed, the significant effects on speed are minor given that neither distance nor duration were different between the groups. Therefore, we can conclude that DMBA does not prevent voluntary wheel running in mice

High Fat High Sugar Diet Reduces Voluntary Wheel Running in Mice Independent of Sex Hormone Involvement

Introduction: Indirect results in humans suggest that chronic overfeeding decreases physical activity with few suggestions regarding what mechanism(s) may link overfeeding and decreased activity. The primary sex hormones are known regulators of activity and there are reports that chronic overfeeding alters sex hormone levels. Thepurpose of this study was to determine if chronic overfeeding altered wheel running through altered sex hormone levels.Materials and Methods: C57BL/6J mice were bred and the pups were weaned at 3-weeks of age and randomly assigned to either a control (CFD) or high fat/high sugar (HFHS) diet for 9–11 weeks depending on activity analysis. Nutritional intake, body composition, sex hormone levels, and 3-day and 2-week wheel-running activity were measured. Additionally, groups of HFHS animals were supplemented with testosterone (males) and 17β-estradiol (females) to determine if sex hormone augmentation altered diet-induced changes in activity.Results: 117 mice (56♂, 61♀) were analyzed. The HFHS mice consumed significantly more calories per day than CFD mice (male: p < 0.0001; female: p < 0.0001) and had significantly higher body fat (male: p < 0.0001; female: p < 0.0001). The HFHS diet did not reduce sex hormone levels, but did significantly reduce acute running-wheel distance in male (p = 0.05, 70 ± 28%) and female mice (p = 0.02, 57 ± 26%). In animals that received hormone supplementation, there was no significant effect on activity levels. Two-weeks of wheel access was not sufficient to alter HFHS-induced reductions in activity or increases in body fat.Conclusion: Chronic overfeeding reduces wheel running, but is independent of the primary sex hormones

NRF2 Alters Mitochondrial Gene Expression in Neonate Mice Exposed to Hyperoxia

Approximately 1 in 10 newborns are born preterm and require supplemental oxygen (O2) in an extrauterine environment following birth. Supplemental O2 can induce oxidative stress that can impair mitochondrial function, resulting in lung injury and increased risk in early life pulmonary diseases. The nuclear factor-erythroid 2 related factor 2 (NRF2) protects the cells from oxidative stress by regulating the expression of genes containing antioxidant response elements and many mitochondrial-associated genes. In this study, we compared Nrf2-deficient (Nrf2−/−) and wild-type (Nrf2+/+) mice to define the role of NRF2 in lung mitochondrial genomic features in late embryonic development in mice (embryonic days, E13.5 and E18.5) versus birth (postnatal day 0, PND0). We also determined whether NRF2 protects lung mitochondrial genome parameters in postnatal mice exposed to a 72 h hyperoxia environment. We found Nrf2−/− embryonic lungs were characterized by decreases in mtDNA copies from E13.5 to E18.5. Interestingly, Nrf2−/− heteroplasmy frequency was significantly higher than Nrf2+/+ at E18.5, though this effect reversed at PND0. In postnatal mice exposed to hyperoxia, we identified three- to four-fold increases in mitochondria-encoded mitochondrial genes, which regulate oxidative phosphorylation. Overall, our findings demonstrate a potentially critical role of NRF2 in mediating long-term effects of hyperoxia on mitochondrial function