title: Effects of exercise training on brain-derived neurotrophic factor in skeletal muscle and heart of rats post myocardial infarction.
abstract: What is the central question of this study? Exercise training increases brain-derived neurotrophic factor (BDNF) in the hippocampus, which depends on a myokine, fibronectin type III domain-containing protein 5 (FNDC5). Whether exercise training after myocardial infarction induces parallel increases in FNDC5 and BDNF expression in skeletal muscle and the heart has not yet been studied. What is the main finding and its importance? Exercise training after myocardial infarction increases BDNF protein in skeletal muscle and the non-infarct area of the LV without changes in FNDC5 protein, suggesting that BDNF is not regulated by FNDC5 in skeletal muscle and heart. An increase in cardiac BDNF may contribute to the improvement of cardiac function by exercise training. Exercise training after myocardial infarction (MI) attenuates progressive left ventricular (LV) remodelling and dysfunction, but the peripheral stimuli induced by exercise that trigger these beneficial effects are still unclear. We investigated as possible mediators fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF) in the skeletal muscle and heart. Male Wistar rats underwent either sham surgery or ligation of the left descending coronary artery, and surviving MI rats were allocated to either a sedentary (Sed-MI) or an exercise group (ExT-MI). Exercise training was done for 4 weeks on a motor-driven treadmill. At the end, LV function was evaluated, and FNDC5 and BDNF mRNA and protein were assessed in soleus muscle, quadriceps and non-, peri- and infarct areas of the LV. At 5 weeks post MI, FNDC5 mRNA was decreased in soleus muscle and all areas of the LV, but FNDC5 protein was increased in the soleus muscle and the infarct area. Mature BDNF (mBDNF) protein was decreased in the infarct area without a change in mRNA. Exercise training attenuated the decrease in ejection fraction and the increase in LV end-diastolic pressure post MI. Exercise training had no effect on FNDC5 mRNA and protein, but increased mBDNF protein in soleus muscle, quadriceps and the non-infarct area of the LV. The mBDNF protein in the non-infarct area correlated positively with ejection fraction and inversely with LV end-diastolic pressure. In conclusion, mBDNF is induced by exercise training in skeletal muscle and the non-infarct area of the LV, which may contribute to improvement of muscle dysfunction and cardiac function post MI.
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Heow Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Monir
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Frans H H
authors.identifier: 0000-0001-8497-4416
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005353:Fibronectins; D012333:RNA, Messenger