Light and electron microscopic analysis of quadriceps muscle cells from euthermic and hibernating edible dormice demonstrated that: 1) the general structure of the muscle (histology, shape and size of myofibres, ratio of fast and slow fibre types) is not affected by hibernation; 2) the fine structure of both cytoplasmic and nuclear constituents is similar in euthermia and hibernation, with the exception of lipid droplets accumulating during lethargy; 3) during hibernation, mitochondria are larger in size with longer cristae, and 4) during hibernation, myonuclei maintain the same amount and distribution of transcripts and transcription factors as in euthermia.
Findings presented here demonstrate the absence of muscle atrophy and gross fibre changes in the edible dormice during hibernation, thereby confirming previous data in the ground squirrel [8, 9], bear [10–12], and bat  showing that muscle mass, myofibre size or number, or the cell content in myofibrils are similar in skeletal muscle throughout the euthermia-hibernation cycle. A novel finding presented in this paper is that the myonucleus, a key organelle for most cellular activities, maintains an active ultrastructural configuration even after several months of immobility.
In hibernating edible dormice, mitochondria only show minor ultrastructural modifications, being larger and with longer cristae; similar changes are present in different tissues of hibernating hazel dormice , possibly due to preferential utilization of lipid as the source of energy during lethargy [14, 25, 26]. In fact, when fatty acids become the main substrate for respiration instead of carbohydrates, mitochondria increase their size and the number of cristae (see  and references therein). Consistently, the close association of muscle cell mitochondria with lipid droplets accumulating in the cytoplasm during hibernation (this study) parallels the increase in fatty acid binding proteins [27, 28]; these changes are probably instrumental to efficient transport of fatty acids to the sites of utilisation. Therefore, the observed mitochondrial changes could help keeping respiration active under the extreme metabolic conditions of lethargy; in accordance, respiratory activity in skeletal muscle mitochondria was found to be similar in hibernating and euthermic ground squirrels . Moreover, maintaining mitochondria in an "active" arrangement would allow hibernating animals to rapidly and fully restore mitochondrial function upon arousal i.e., a phase of exploding energy demand. This is of special relevance for skeletal muscle cells because all mammalian hibernators re-warm at periodic intervals during winter [30, 31], shivering playing a key role in rising body temperature during arousal.
Previous studies on cell nuclei of different tissues from the edible and hazel dormice demonstrated quali-quantitative changes in PF and PG as well as architectural and molecular modifications of nucleoli (e.g. [22, 32, 33]); in addition, several different nuclear bodies involved in the storage/assembly of RNA processing factors have been shown to appear or increase in number during hibernation . On the contrary, myonuclei of hibernating dormice exhibit an "active" appearance: in fact, RNP structural constituents involved in pre-mRNA processing (which are very sensitive to changes in transcriptional activity, see e.g. ), do not vary in their amount or distribution. Accordingly, the amorphous bodies, a typical nuclear body in hibernation , occur in the nucleoplasm of myonuclei in very limited amounts (2% of sectioned myonuclei showing one amorphous body vs 25% sectioned nuclei of hepatocytes presenting one to three amorphous bodies). Moreover, no change apparently occurs in the nucleolus, the site of rRNA transcription and ribosome assembly, which undergoes very rapid change in morphology and function according to changing cell metabolism (see e.g. ). During hibernation, myonuclei also maintain the same euthermic level of transcripts and transcription factors; this finding suggests either preservation of high functional rate in the nucleus or the establishment of a nuclear configuration able to quickly and massively restore the transcriptional activity where needed. The latter hypothesis is supported by evidence showing accumulation of phosphorylated polymerase II in hibernating ground squirrels in the presence of an overall decrease of transcriptional activity in skeletal muscle . Accordingly, it has been recently reported [37, 38] that mRNA transcripts accumulate during hibernation and quickly disappear at early arousal in various tissues of different hibernators, thus supporting the view that modulation of transcriptional activity is part of a far-reaching program leading to the rapid increase of protein synthesis upon arousal.
In skeletal muscle cells of hibernating mammals, the expression levels of major myofibrillar proteins are retained  or even up-regulated , so that protein synthesis and breakdown are balanced . The current observations in the edible dormouse strongly support the concept that, even in deep hibernation, skeletal muscle cells maintain their synthetic activity at such a rate to effectively counteract muscle wasting (mind that degradation processes also slow down during hibernation) as well as support their ability to quickly restore in full the contractile function. The ongoing low-rate activity in skeletal muscle cells during hibernation could be related to low transmitter release at the neuromuscular junction, which has been found in hindlimb of the golden hamster , as well as to the trophic effect of enhanced purinergic activity . In addition, the strenuous muscle shivering rapidly raising body temperature and metabolic rate at every periodic arousal could also help to prevent muscle atrophy by acting as intensive physical exercise [13, 43].