Brain-derived neurotrophic factor is associated with human muscle satellite cell differentiation in response to muscle-damaging exercise

Bryon R. McKay, Joshua P. Nederveen, Stephen A. Fortino, Tim Snijders, Sophie Joanisse, Dinesh A. Kumbhare, Gianni Parise*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Muscle satellite cell (SC) regulation is a complex process involving many key signalling molecules. Recently, the neurotrophin brain-derived neurotropic factor (BDNF) has implicated in SC regulation in animals. To date, little is known regarding the role of BDNF in human SC function in vivo. Twenty-nine males (age, 21 +/- 0.5 years) participated in the study. Muscle biopsies from the thigh were obtained prior to a bout of 300 maximal eccentric contractions (Pre), and at 6 h, 24 h, 72 11, and 96 h postexercise. BDNF was not detected in any quiescent (Pax7(+)/MyoD(-))SCs across the time-course. BDNF colocalized to 39% +/- 5% of proliferating (Pax7(+)/MyoD(-)) cells at Pre, which increased to 84% +/- 3% by 96 h (P < 0.05). BDNF was only detected in 13% +/- 5% of differentiating (Pax7(+)/MyoD(-)) cells at Pre, which increased to 67% +/- 4% by 96 h (P < 0.05). The number of myogenin(+) cells increased 95% from Pre (1.6 +/- 0.2 cells/100 myofibres (MF)) at 24 h (3.1 +/- 0.3 cells/100 MF) and remained elevated until 96 h (cells/100 MF), P < 0.05. The proportion of BDNF+/mnyogenin(+) cells was 26% +/- 0.3% at Pre, peaking at 24 11 (49% +/- 3%, P < 0.05) and remained elevated at 96 h (P < 0.05). These data are the first to demonstrate an association between SC proliferation and differentiation and BDNF expression in humans in vivo, with BDNF colocalization to SCs increasing during the later stages of proliferation and early differentiation.

Novelty

BDNF is associated with SC response to muscle injury.

BDNF was not detected in nonactivated (quiescent) SCs.

BDNF is associated with late proliferation and early differentiation of SCs in vivo in humans.

Original languageEnglish
Pages (from-to)581-590
Number of pages10
JournalApplied Physiology Nutrition and Metabolism-Physiologie appliquee nutrition et metabolisme
Volume45
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • Pax7
  • satellite cells
  • brain-derived neurotrophic factor
  • muscle
  • damage
  • myogenic regulatory factors
  • SKELETAL-MUSCLE
  • STEM-CELL
  • GENE-EXPRESSION
  • BDNF
  • REGENERATION
  • POTENTIATION
  • CONTRACTION
  • ACTIVATION
  • EXPANSION
  • SURVIVAL

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