Examination of chronic BDNF treatment and endurance training on skeletal muscle adaptations

Abstract

Brain-derived neurotrophic factor (BDNF) was recently described as a contraction-induced protein, produced by muscle and released into circulation, having autocrine and endocrine actions. Our understanding of BDNFs role in skeletal muscle is limited; however, it may play a role in how muscle adapts to exercise. Thus far it is known that BDNF expression varies between skeletal muscle fiber types but is predominately found in oxidative muscle. Acute exercise bouts increase circulating and skeletal muscle BDNF, and BDNF treatment of isolated muscles increases fat oxidation through activation of AMPK. The effects of endurance training and BDNF administration on these parameters have yet to be examined. This study's purpose was to compare chronic subcutaneous BDNF treatment with endurance training in mice. A secondary purpose was to deterimine if BDNF treatment could enhance endurance training adpatations. Male C57BL6 mice were randomly assigned to one of four groups (n=12/group): 1) control (CON); 2) endurance training (ET; treadmill running 1hour/day, 5days/wk); 3) BDNF (BDNF; 0.5 mg/kg·bw, 5days/wk); 4) endurance training and BDNF (ET+BDNF) for 8 weeks. Results showed a main effect of BDNF on reducing body mass (p<0.05) and food intake (p<0.05). The treadmill test to exhaustion demonstrated a main effect of BDNF (p<0.01) and ET (p<0.0001) on increasing exercise capacity (p<0.05), further ET+BDNF increased time to exhaustion compared to the ET group (p<0.001). In vitro contractile assessment of the EDL revealed BDNF treatment resulted in similar increases in the max rate of relaxation as ET alone. EDL force-frequency analysis showed ET+BDNF produced higher force than CON and BDNF (p<0.05). No effect of BDNF on soleus contractile properties was observed. BDNF increased EDL COXIV and CS content (p=0.06), however not to the same extent as ET (p<0.05). No effect of BDNF on mitochondrial markers was observed in the soleus. The current study provides novel data regarding the effect of chronic BDNF treatment and exercise on appetite regulation, exercise capacity, and mitochondrial markers in a healthy mouse model. These results demonstrate that BDNF may contribute to skeletal muscle adaptations observed with endurance training. Further work is needed to determine if BDNF is required for these adaptations.