Endothelial cells are an important source of BDNF in rat skeletal muscle

Marina Cefis,Remi Chaney,Christine Marie,Philippe Garnier,Anne Prigent-Tessier,Aurore Quirié,Clélia Santini

doi:10.1038/s41598-021-03740-8

Abstract

BDNF (brain-derived neurotrophic factor) is present in skeletal muscle, controlling muscular metabolism, strength and regeneration processes. However, there is no consensus on BDNF cellular source. Furthermore, while endothelial tissue expresses BDNF in large amount, whether endothelial cells inside muscle expressed BDNF has never been explored. The aim of the present study was to provide a comprehensive analysis of BDNF localization in rat skeletal muscle. Cellular localization of BDNF and activated Tropomyosin-related kinase B (TrkB) receptors was studied by immunohistochemical analysis on soleus (SOL) and gastrocnemius (GAS). BDNF and activated TrkB levels were also measured in muscle homogenates using Western blot analysis and/or Elisa tests. The results revealed BDNF immunostaining in all cell types examined with a prominent staining in endothelial cells and a stronger staining in type II than type I muscular fibers. Endothelial cells but not other cells displayed easily detectable activated TrkB receptor expression. Levels of BDNF and activated TrkB receptors were higher in SOL than GAS. In conclusion, endothelial cells are an important and still unexplored source of BDNF present in skeletal muscle. Endothelial BDNF expression likely explains why oxidative muscle exhibits higher BDNF levels than glycolytic muscle despite higher the BDNF expression by type II fibers.

Highlights

The main results are that (i) muscular fibers, satellite cells, motor neurons and endothelial cells simultaneously express BDNF, yet with a prominent expression by endothelial cells and a more pronounced BDNF expression by type II than type I muscular fibers, (ii) that the muscular expression of activated TrkB receptor is preponderantly attributable to endothelial cells as compared to other cells
BDNF localization in the skeletal muscle has not been extensively studied. This is surprising as the first detection of BDNF mRNA in skeletal muscle was reported in 1 9936
The present study showed that myofibers, satellite cells and axonal processes constitutively expressed BDNF irrespective of the muscle type and that BDNF expression was higher in type II than type I fibers[17,18]

Summary

Introduction

As reported for SOL, BDNF staining was detected in satellite cells, neurons and endothelial cells (data not shown). The differential expression of BDNF in type II versus type I fibers combined with the strong expression of BDNF by endothelial cells led us to compare BDNF levels in SOL versus GAS muscle.

Objectives

Results

Conclusion