Denervation in murine fast-twitch muscle: short-term physiological changes and temporal expression profiling

Abstract

Denervation deeply affects muscle structure and function, the alterations being different in slow and fast muscles. Because the effects of denervation on fast muscles are still controversial, and high-throughput studies on gene expression in denervated muscles are lacking, we studied gene expression during atrophy progression following denervation in mouse tibialis anterior (TA). The sciatic nerve was cut close to trochanter in adult CD1 mice. One, three, seven, and fourteen days after denervation, animals were killed and TA muscles were dissected out and utilized for physiological experiments and gene expression studies. Target cDNAs from TA muscles were hybridized on a dedicated cDNA microarray of muscle genes. Seventy-one genes were found differentially expressed. Microarray results were validated, and the expression of relevant genes not probed on our array was monitored by real-time quantitative PCR (RQ-PCR). Nuclear- and mitochondrial-encoded genes implicated in energy metabolism were consistently downregulated. Among genes implicated in muscle contraction (myofibrillar and sarcoplasmic reticulum), genes typical of fast fibers were downregulated, whereas those typical of slow fibers were upregulated. Electrophoresis and Western blot showed less pronounced changes in myofibrillar protein expression, partially confirming changes in gene expression. Isometric tension of skinned fibers was little affected by denervation, whereas calcium sensitivity decreased. Functional studies in mouse extensor digitorum longus muscle showed prolongation in twitch time parameters and shift to the left in force-frequency curves after denervation. We conclude that, if studied at the mRNA level, fast muscles appear not less responsive than slow muscles to the interruption of neural stimulation.

Microarray gene expression analysis in atrophying rainbow trout muscle: a unique nonmammalian muscle degradation model

“…This number represents ϳ1% of the total number of probes present on the chip. Using gene ontology to classify these genes, based on molecular function, resulted in gene sets that represent a specific program of transcriptional changes that are largely similar to the well-studied programs of mammalian muscle atrophy (41,57). In addition, a number of new and unexpected genes, perhaps unique to the RBT wastage process, are reported here for the first time.…”

“…Glucose sparing in RBT may result from insulin resistance because of the prolonged energetic challenge from the reproductive demand. Reduced transcription of genes involved in glucose utilization is a common feature of muscle atrophy induced by fasting, the systemic diseases diabetes, cancer cachexia, and renal failure (41) and muscle disuse (57). Insulin resistance is a common feature of all forms of muscle degradation and is the direct trigger of accelerated muscle proteolysis (32,41).…”

Modifying muscle mass – the endocrine perspective

“…Denervation of muscle (often with associated aberrant reinnervation) is regarded as a potent trigger to sarcopeniaboth associated with ageing and neuromuscular disordersand has recently been examined at the molecular level (Raffaello et al 2006). The use of IGF-I electroporation, recombinant human IGF-I and the peptide representing mechano-growth factor (MGF) have all been considered for ameliorating such neuromuscular conditions, including muscular dystrophy and motor neuron disease (Lynch 2004).…”

Effect of locomotor training on muscle performance in the context of nerve–muscle communication dysfunction

“…This is in line with previous studies that examined soleus and TA muscles in mice. 15,22 The deficit in absolute maximal force (À84%) was caused by both a reduced specific maximal force and a lower soleus muscle weight. We also observed that the effect of denervation was more severe for the soleus than the TA (À84% vs. À56% for absolute maximal force), confirming previous studies.…”