Skeletal muscle denervation investigations: selecting an experimental control wisely

Unilateral denervation is widely used for studies investigating mechanisms of muscle atrophy. The “contralateral-innervated muscle” is a commonly used experimental control in denervation studies. It is not clear whether denervation unilaterally alters the proteolytic system in the contralateral-innervated muscles. Therefore, the objectives of this rapid report are 1) to determine whether unilateral denervation has an effect on the proteolytic system in contralateral-innervated control muscles and 2) to identify the changes in proteasome properties in denervated muscles after 7- and 14-day tibial nerve transection with either the contralateral-innervated muscles or intact muscles from nonsurgical mice used as the experimental control. In the contralateral-innervated muscles after 7 and 14 days of nerve transection, the proteasome activities and content are significantly increased compared with muscles from nonsurgical mice. When the nonsurgical mice are used as the experimental control, a robust increase in proteasome properties is found in the denervated muscles. This robust increase in proteasome properties is eliminated when the contralateral-innervated muscles are the experimental control. In conclusion, there is a crossover effect from unilateral denervation on proteolytic parameters. As a result, the crossover effect on contralateral-innervated muscles must be considered when an experimental control is selected in a denervation study.