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The brain‐derived neurotrophic factor (BDNF) regulates skeletal muscle regeneration and is mis‐regulated in dystrophic muscle
Author(s) -
Clow Charlene Grace,
Mousavi Kambiz,
Parks Robin J.,
Jasmin Bernard J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1306-a
Subject(s) - skeletal muscle , regeneration (biology) , neurotrophic factors , cardiotoxin , brain derived neurotrophic factor , myogenesis , gene knockdown , myosin , myocyte , endocrinology , biology , medicine , microbiology and biotechnology , tropomyosin receptor kinase b , muscular dystrophy , c2c12 , cell culture , genetics , receptor
Our recent studies have shown that BDNF is highly expressed in skeletal muscle satellite cells (J. Neurosci., 26: , 2006). Additionally, BDNF depletion by siRNA results in precocious differentiation of myoblasts. In order to determine whether BDNF plays similar roles in vivo, we designed several complementary experiments. First, we examined mouse muscle induced to degenerate/regenerate following cardiotoxin injection. We show that BDNF expression is significantly increased during early phases of regeneration but that its expression decreases (to control levels) within 5 days post‐injection. Moreover, BDNF down‐regulation coincides with increased expression of several markers of differentiation. Constitutive in vivo expression of siRNAs to knockdown BDNF in regenerating muscles results in enhanced differentiation as demonstrated by the pattern of myosin heavy chain isoforms expressed. Given the therapeutic importance of regeneration for treating various muscle diseases, we also examined the expression profile of BDNF in dystrophic muscles from mdx mice. In comparison to muscles from wildtype animals, mdx mouse muscles consistently display greater levels of BDNF. Finally, genetic inactivation of BDNF in developing skeletal muscle using Cre‐lox technology will also allow us to determine the impact of BDNF expression during embryonic and neonatal muscle development. Funded by MDA and CIHR.