Muscle atrophy and regeneration associated with behavioural loss and recovery of function after sciatic nerve crush

Abstract

Aim To resolve timing and coordination of denervation atrophy and the re‐innervation recovery process to discern correlations indicative of common programs governing these processes. Methods Female Sprague‐Dawley (SD) rats had a unilateral sciatic nerve crush. Based on longitudinal behavioural observations, the triceps surae muscle was analysed at different time points post‐lesion. Results Crush results in a loss of muscle function and mass (−30%) followed by a recovery to almost pre‐lesion status at 30 days post‐crush (dpc). There was no loss of fibres nor any significant change in the number of nuclei per fibre but a shift in fibres expressing myosins I and II that reverted back to control levels at 30 dpc. A residual was the persistence of hybrid fibres. Early on a CHNR ‐ε to ‐γ switch and a re‐expression of embryonic MyHC showed as signs of denervation. Foxo1, Smad3, Fbxo32 and Trim63 transcripts were upregulated but not Myostatin, InhibinA and ActivinR2B. Combined this suggests that the mechanism instigating atrophy provides a selectivity of pathway(s) activated. The myogenic differentiation factors (MDFs: Myog, Myod1 and Myf6) were upregulated early on suggesting a role also in the initial atrophy. The regulation of these transcripts returned towards baseline at 30 dpc. The examined genes showed a strong baseline covariance in transcript levels which dissolved in the response to crush driven mainly by the MDFs. At 30 dpc the naïve expression pattern was re‐established. Conclusion Peripheral nerve crush offers an excellent model to assess and interfere with muscle adaptions to denervation and re‐innervation.

Identification of Potential miRNA-mRNA Regulatory Network in Denervated Muscular Atrophy by Bioinformatics Analysis

“…Myod1 has been reported signi cantly up-regulated early after sciatic nerve compression, indicating that it started to play a role in initial muscle atrophy [32]. Studies have shown that mir-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts in vitro and contributes to skeletal muscle atrophy in response to different atrophic stimuli in vivo [27].…”

Identification of Potential miRNA-mRNA Regulatory Network in Denervated Muscular Atrophy by Bioinformatics Analysis

“…It regulates muscle cell differentiation by inducing cell cycle arrest, which is a prerequisite for the initiation of myogenesis. Myod1 has been reported signi cantly up-regulated early after sciatic nerve compression, indicating that it started to play a role in initial muscle atrophy [23].RELA proto-oncogene (Rela), a component of the NFkappa B complex, and nuclear factor kappa B subunit 1 (Nfkb1) jointly constitute a transcriptionally active NF-kappa B dimer, which participates in the expression of genes in the processes of immunity, in ammation, and apoptosis [24]. Nuclear factor Kappa B (NF-κB) has also been reported to be a prominent signaling molecule in the pathogenesis of skeletal muscle atrophy, and many muscular atrophy-related genes, including MuRF1, MyoD and cyclin D ubiquitin-binding enzyme (E2), are its target gene [25].…”

Identification of Potential miRNA-mRNA Regulatory Network in Denervated Muscular Atrophy by Bioinformatics Analysis

“…Myod1 has been reported signi cantly up-regulated early after sciatic nerve compression, indicating that it started to play a role in initial muscle atrophy [23].RELA proto-oncogene (Rela), a component of the NFkappa B complex, and nuclear factor kappa B subunit 1 (Nfkb1) jointly constitute a transcriptionally active NF-kappa B dimer, which participates in the expression of genes in the processes of immunity, in ammation, and apoptosis [24]. Nuclear factor Kappa B (NF-κB) has also been reported to be a prominent signaling molecule in the pathogenesis of skeletal muscle atrophy, and many muscular atrophy-related genes, including MuRF1, MyoD and cyclin D ubiquitin-binding enzyme (E2), are its target gene [25].…”