Myosin heavy chain isoform mRNA and protein levels after long-term paralysis

Area of Science:

• Muscle physiology
• Neuroscience
• Molecular biology

Background:

• Paralysis due to spinal cord injury (SCI) leads to profound muscle disuse.
• Understanding long-term molecular adaptations in paralyzed muscles is crucial for developing therapeutic strategies.
• Myosin Heavy Chain (MyHC) isoforms determine muscle fiber type and contractile properties.

Purpose of the Study:

• To investigate the long-term effects of spinal cord transection (ST) on muscle phenotypic mRNA and protein expression.
• To analyze changes in MyHC isoform mRNA and protein levels in rat soleus and medial gastrocnemius (MG) muscles post-ST.

Main Methods:

• Rats underwent spinal cord transection (ST).
• Soleus and medial gastrocnemius (MG) muscles were analyzed for MyHC-I, MyHC-IIa, MyHC-IIx, and MyHC-IIb mRNA and protein expression.
• Quantitative analysis of gene and protein expression levels was performed.

Main Results:

• In soleus muscle, ST caused a significant decrease in MyHC-I mRNA and a substantial increase in MyHC-IIa and MyHC-IIx mRNA.
• MyHC-IIb mRNA was expressed at low levels post-ST, suggesting disuse alone does not strongly induce MyHC-IIb.
• mRNA adaptations in the soleus preceded corresponding protein level changes.
• MG muscle showed only a reduction in MyHC-I protein, with other MyHC isoforms remaining largely unchanged, indicating insufficient stimulus for phenotypic shift.

Conclusions:

• Spinal cord transection induces significant long-term molecular alterations in hindlimb muscles, particularly shifting the soleus muscle phenotype towards faster MyHC isoforms.
• mRNA expression changes precede protein adaptations, offering a potential window for early therapeutic intervention.
• The medial gastrocnemius muscle's relative resistance to phenotypic change suggests that reduced load-bearing alone may not be sufficient to induce significant muscle fiber type transitions.