BDNF Is Expressed in Skeletal Muscle Satellite Cells and Inhibits Myogenic Differentiation

Abstract

In skeletal muscle, brain-derived neurotrophic factor (BDNF) has long been thought to serve as a retrograde trophic factor for innervating motor neurons throughout their lifespan. However, its localization in mature muscle fibers has remained elusive. Given the postulated roles of BDNF in skeletal muscle, we performed a series of complementary experiments aimed at defining the localization of BDNF and its transcripts in adult muscle. By reverse transcription-PCR, in situ hybridization, and immunofluorescence, we show that BDNF, along with the receptor p75 NTR , is not expressed at significant levels within mature myofibers and that it does not accumulate preferentially within subsynaptic regions of neuromuscular junctions. Interestingly, expression of BDNF correlated with that of Pax3, a marker of muscle progenitor cells, in several different adult skeletal muscles. Additionally, BDNF was expressed in Pax7ϩ satellite cells where it colocalized with p75 NTR . In complementary cell culture experiments, we detected high levels of BDNF and p75 NTR in myoblasts. During myogenic differentiation, expression of BDNF became drastically reduced. Using small interfering RNA (siRNA) technology to knock down BDNF expression, we demonstrate enhanced myogenic differentiation of myoblasts. This accelerated rate of myogenic differentiation seen in myoblasts expressing BDNF siRNA was normalized by administration of recombinant BDNF. Collectively, these findings show that BDNF plays an important regulatory function during myogenic differentiation. In addition, the expression of BDNF in satellite cells is coherent with the notion that BDNF serves a key role in maintaining the population of muscle progenitors in adult muscle.

Cerebral 5-HT2A Receptor and Serotonin Transporter Binding in Humans Are Not Affected by the val66met BDNF Polymorphism Status or Blood BDNF Levels

“…Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophins and is primarily produced in neurons and glia cells and to a lesser extent in endothelial cells (Leventhal et al, 1999), leucocytes (Kerschensteiner et al, 1999), and satellite cells in skeletal muscles (Mousavi and Jasmin, 2006). Brain-derived neurotrophic factor is important for growth of the central nervous system during fetal development, whereas in adults, BDNF is primarily involved in synaptic plasticity, neurogenesis, and neuronal survival (for review, see Waterhouse and Xu, 2009).…”

Apoptotic Effects of Reduced Brain Derived Neurotrophic Factor (BDNF) on Mouse Liver and Kidney

“…It has been reported that the BDNF and TrkB receptors are also expressed in many non-neuronal tissues including muscle, thymus, vascular smooth muscle cells, lung and spleen 5,10,14,16,18,19,36 . However, in a number of different studies it has been found that BDNF receptors are not expressed in peripheral tissues.…”

“…BDNF expression was primarily detected in the hippocampus, cortex, and basal forebrain, areas where the brain performs learning, memory, and high-level thinking tasks 13 . Later, it was found that BDNF was presented not only in the brain but also in peripheral tissues such as skeletal muscle, adipose tissue, kidneys, liver and prostate 5,10,11,[14][15][16][17][18][19][20][21] .…”

Androgen regulation of axon growth and neurite extension in motoneurons

“…In some cases, these cells may play a role by producing various neurotrophic factors (or their receptors), which may also be regulated by androgens. For example, skeletal muscle satellite cells produce brain derived neurotrophic factor (BDNF; Mousavi and Jasmin, 2006), and levels of both BDNF and its receptor TrkB are controlled by androgens in at least some motoneurons (Osborne et al, 2007;Ottem et al, 2007). It is thought that BDNF produced by the muscle acts as a retrogradely transported trophic factor to support motoneurons throughout their lifespan.…”