Muscle plasticity in hibernating ground squirrels (Spermophilus lateralis) is induced by seasonal, but not low-temperature, mechanisms

Abstract

During hibernation, ground squirrels (Spermophilus lateralis) show unusually altered expression of skeletal muscle myosin heavy-chains. Some muscle groups show transitions from fast to slower myosin isoforms despite atrophy, which are not predicted from other mammalian studies of inactivity. We measure myosin protein and mRNA expression, and the mRNA expression of genes important in atrophy and metabolism in a time-course of muscle plasticity prior to, and during extended hibernation. We also investigate the role of strictly low-temperature processes by comparing torpid individuals at 20 and 4°C. Shifts in myosin isoform expression happen at both temperatures, before the onset of torpor, or within the first month of torpor, in all muscles demonstrating isoform remodeling. Skeletal muscle atrophy is greatly attenuated in this hibernating species, and even may be absent in some muscles. When present, atrophy develops early in hibernation, and does not progress in the final 3 months of torpor. Myostatin mRNA is down-regulated 50-75% in the soleus and diaphragm, two important muscles that are spared of atrophy. The transcription factor FOXO1, which spurs proteolytic degradation of contractile proteins through regulation of the ubiquitin ligase MAFbx, is also generally down-regulated, and may contribute to reduced atrophy. Hypoxia-inducible factor (HIF-1α) mRNA expression was reduced 50% in some muscles, while elevated more than 300% in others. Our collective findings most strongly support early, seasonal, phenotype changes in skeletal muscles which are not uniquely confined to, or prompted by, torpor at 4°C. Such seasonal control of myosin would be a novel mechanism in mammalian skeletal muscle, which otherwise is most susceptible to mechanical loading and limb-activity patterns.

Scaling matters: incorporating body composition into Weddell seal seasonal oxygen store comparisons reveals maintenance of aerobic capacities

“…These findings suggest that Weddell seals may be physiologically "programmed" to withstand periods of reduced activity while maintaining muscle integrity. Wild animals may need to forage effectively and escape predation after such periods of reduced activities, and indeed, similar patterns of atrophy resistance have been observed in hibernating bats and rodents, and winter lethargy in bears (Lohuis et al 2007;Hershey et al 2008;Lee et al 2008;Nowell et al 2011). Despite being composed of primarily slow-oxidative fibers that are particularly vulnerable to atrophy, Weddell seal muscles maintained aerobic MHC profiles.…”

Mechanisms underlying inhibition of muscle disuse atrophy during aestivation in the green-striped burrowing frog, Cyclorana alboguttata

“…James et al (James et al, 2013) reported no loss of mass or tension in soleus muscle of S. tridecemlineatus following three months of hibernation, whereas a 14% loss was found in the gastrocnemius and 43% loss in the semitendinous muscles of the golden-mantled ground squirrel (Spermophilus lateralis) (Wickler et al, 1991). Muscle atrophy develops early on in hibernating S. lateralis but does not advance in the final 3 months (Nowell et al, 2011), a result which is similar to that which occurs during prolonged bed rest in humans (Adams et al, 2003;Phillips et al, 2009). …”

“…Brooks and coworkers demonstrated that myostatin protein levels in mixed hindlimb muscle of S. tridecemlineatus were largely constant throughout torpor relative to controls, but increased significantly during arousal (Brooks et al, 2011) while in hibernating S. lateralis, a significant reduction in myostatin gene expression was found in soleus and diaphragm muscles, but not in limb muscles with fast-type fibres (Nowell et al, 2011 …”

“…For example, recent studies have emphasised the importance of maintaining protein synthesis in hibernating muscle via activation of the mammalian target of rapamycin (mTOR) signalling cascade (e.g. Andres-Mateos et al, 2013;Fedorov et al, 2014;Lee et al, 2010;Nowell et al, 2011). The mTOR is a major effector of cell growth and proliferation via the regulation of protein synthesis through a multitude of downstream targets.…”

“…The mTOR is a major effector of cell growth and proliferation via the regulation of protein synthesis through a multitude of downstream targets. S. lateralis squirrels decrease myostatin expression (an mTOR inhibitor) in skeletal muscles that are resistant to winter atrophy, potentially facilitating mTOR signalling by suppressing this inhibition (Nowell et al, 2011), while periodic arousals from winter hibernation in bats appears to be associated with oscillations in the activation of mTOR (Lee et al, 2010).…”