Brain mRNA Expression Changes Following Orchidectomy Are Not Associated with Physical Activity Levels in Male Mice

Physical activity is a complex phenotypical behavior that is largely associated with improved resistance to disease and health disparities. Despite the well‐established link between physical activity and health, few Americans—5% of males and 3% of females—routinely accumulate minimum recommended amounts of moderate and vigorous physical activity. Delineating the mechanisms that biologically regulate physical activity, therefore, is an important health‐related concern. The purpose of this study was to assess brain mRNA levels in male mice surgically induced—via orchidectomy—to exhibit low sex steroid concentrations and reduced physical activity levels. Male C57BL6/j mice (n=28) were acquired at 8 weeks of age and were housed individually with access to computer‐monitored running wheels. Following a brief wheel running acclimation period, mice underwent sham (control, n=12; 2 mice were removed from study for health‐related reasons) or real (treatment, n=14) bilateral orchidectomy procedures. Following a ten‐day surgical recovery period, all mice were allowed to run freely on in‐cage running wheels which continually monitored wheel running distance (km), duration (min), and speed (m·min −1 ). Data were collected for ten consecutive days to generate average values for each physical activity index. At the end of the study, all mice were killed and brain tissues were harvested. Reverse transcription followed by polymerase chain reaction assays were conducted to estimate the levels of mRNA transcripts hypothesized to be involved in regulating physical activity patterns. Genes of interested included drd2, drd4, hctr2, htr2c, and slc18a2. Computational analyses were completed to compare relative normalized expression (RNE) difference between control and treatment animals. For genes that were different between the control and the treatment groups, a correlation analysis was conducted to assess the association between wheel running distance and mRNA levels. Mice with low levels of sex steroids induced by orchidectomy (distance: 3.32±2.26 km) ran significantly less than physiologically intact mice [(distance: 7.94±1.84 km), (t(22)=5.4, p=0.00002)]. Both drd2 (RNE=0.509, p=0.008) and slc18a2 (RNE=2.348, p=0.017) exhibited altered mRNA expression in treatment animals following orchidectomy, however, neither gene exhibited a strong linear association with wheel running distance (drd2: r=0.26 and slc18a2: r=0.08). In conclusion, removal of the tissues that act as major producers of the sex steroids in mice resulted in reductions in wheel running activity and in changes to drd2 and slc18a2 gene expression. Although both changes appear to result from alterations to the sex steroid levels, these changes do not appear to be concomitant, indicating that the regulatory pathway for physical activity behavior associated with low levels of the sex steroids stems from other biochemical and biological changes. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .