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Brain-derived Neurotrophic Factor Pathway after Downhill and Uphill Training in Rats


Medicine & Science in Sports & Exercise: January 2019 - Volume 51 - Issue 1 - p 27–34
doi: 10.1249/MSS.0000000000001771

Introduction The elevation of brain-derived neurotrophic factor (BDNF) levels in the brain and the subsequent phosphorylation of its cognate tropomyosin-related kinase B (TrkB) receptors at tyrosine 816 (pTrkBtyr816) are largely involved in the positive effect of aerobic exercise on brain functioning. Although BDNF levels were reported to increase in proportion with exercise intensity, the effect of the type of contraction is unknown. Therefore, the cerebral BDNF/TrkB pathway was investigated after uphill and downhill treadmill activities at equivalent intensity to preferentially induce eccentric and concentric contractions, respectively.

Methods A treadmill activity (30 min·d−1 for seven consecutive days) either in a horizontal position at two different speeds to modulate intensity (experiment 1) or at three different inclinations (null, −10%, and +5%) but at equivalent intensity to modulate the type of contraction (experiment 2) was induced in rats. Both experiments included sedentary rats. Levels of BDNF, pTrkBtyr816, synaptophysin (marker of synaptogenesis), endothelial nitric oxide synthase phosphorylated at serine 1177 (peNOSser1177), and c-fos levels (indicators of elevation in blood flow in the cerebrovasculature and neuronal activity, respectively) were measured in motor- and cognition-related brain regions using Western blotting analysis.

Results Experiment 1 indicated that treadmill activity induces an intensity-dependent increase in peNOSser1177, c-fos, and BDNF levels. Experiment 2 showed that intensity of exercise as well as activation of the cerebral BDNF pathway, and synaptogenesis did not differ among horizontal, uphill, and downhill treadmill activities.

Conclusion The cerebral response of the BDNF pathway to a treadmill activity is dependent on exercise intensity, but not on the type of contraction (eccentric vs concentric).

1INSERM U1093 CAPS, Burgundy and Franche-Comté University, Dijon, FRANCE;

2Department of Neurology, Regional University Hospital Center of Dijon, Dijon, FRANCE; and

3EA4267 PEPITE, (EPSI), Burgundy and Franche-Comté University, Besançon, FRANCE

Address for correspondence: Martin Pedard, INSERM U1093, UFR des Sciences de Santé, 7 boulevard Jeanne d’Arc, 21000 DIJON, France; E-mail:

Submitted for publication May 2018.

Accepted for publication August 2018.

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© 2019 American College of Sports Medicine