The effect of denervation on the molecular clock in skeletal muscle

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We recently identified the circadian transcriptome in mouse skeletal muscle. The primary objective of this study was to test the hypothesis that innervation is required to maintain oscillation of the circadian molecular clock in muscle. A second objective was to determine if the phase of the molecular clock is the same in different muscles. Using the Period‐2:Luciferase mouse, the tibialas anterior was denervated (d‐TA) by sectioning the common peroneal nerve on one leg with the contralateral leg serving as a sham operated control. Following two weeks of denervation, various muscles and liver were collected from three animals every four hours for 24 hr. RT‐PCR analysis revealed that the expression pattern of components of the molecular clock (Bmal1, Per2 and Clock) as well as Myod1, a clock‐controlled gene, was altered in the d‐TA compared to i‐TA. Luciferase activity, reflecting Per2 protein expression, of the d‐TA was significantly elevated at each time point in comparison to inneravted‐TA (i‐TA), though the time of peak expression remained unchanged. In the heart, diaphragm and liver, peak luciferase activity peaked four hours later than what was observed in hindlimb muscles suggesting the phase of the clock is slightly different in these tissues. Collectively, these results indicate loss of neural input causes alterations in the molecular clock in adult skeletal muscle.KAE (AR045617) and JJM (AR053641)