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First published online September 19, 2008
Journal of Experimental Biology 211, iii (2008)
Copyright © 2008 The Company of Biologists Limited
doi: 10.1242/jeb.010991

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Outside JEB

MYONUCLEI ARE NOT LOST DURING MUSCLE ATROPHY

Jonathan A. W. Stecyk

University of Oslo

jonathan.stecyk{at}imbv.uio.no

We have all experienced the fact that skeletal muscles can change size. When we go to the gym and lift weights, our muscles get bigger. However, when we are lazy and stop working out, our muscles decrease in size. Such muscle shrinkage is termed disuse atrophy and, currently, the only way to build the muscle up again is to increase physical activity and nerve-evoked contractile activity. Muscles also deteriorate with numerous neuromuscular disorders that medical research is endeavoring to cure.

A change in muscle size normally results from an alteration of the size of the individual muscle cells (otherwise known as muscle fibers), which contain numerous nuclei (called myonuclei). The classical belief is that muscle cell size is closely correlated to the number of myonuclei, and that a reduction of muscle fiber size is accompanied by a regulated reduction (i.e. apoptosis) of myonuclei. Thus, a loss of nuclei during disuse atrophy implies that the recovery of muscle strength requires the nuclei to be replenished by muscle satellite cells (the muscle's stem cells). Further, this notion dictates that potential intervention and treatment therapies for neuromuscular disorders should involve activation of the satellite cells or interference of the apoptotic pathways. However, it is likely that the classical view of muscle disuse atrophy needs to be revised, given a recent publication by Jo Bruusgaard and Kristian Gundersen in The Journal of Clinical Investigation.

The team from the University of Oslo, Norway, decided to examine the phenomenon of muscle disuse atrophy using an in vivo time-lapse microscopy technique. First, the team stained myonuclei of both slow- and fast-twitch leg muscle fibers in live mice by transfecting the mice with a plasmid encoding green fluorescent protein (GFP) that localized to muscle nuclei. Subsequently, they inactivated the leg muscles of the mice by denervating the muscle by severing the sciatic nerve, blocking nerve impulses to the muscle with the voltage-gated sodium channel blocker tetrodotoxin, or mechanically unloading the muscle. Following these procedures, the team monitored changes in fiber size and number of myonuclei in the same muscle segment over several days and weeks.

Astonishingly, despite a greater than 50% reduction in the cross-sectional area of the muscle fibers following the inactivation techniques, the team did not observe any loss of myonuclei. Even though the muscle fibers were inactivated, by denervation, nerve impulse block or mechanical unloading, the number of myonuclei in individual muscle fibres did not decrease. Thus the team discovered that, in contrast with the classical belief, muscle nuclei are not lost during disuse. Indeed, the team observed high numbers of nuclei undergoing regulated reduction by apoptosis in inactive muscles, but the apoptosis was confined to the nuclei in satellite cells and surrounding stromal cells, not those situated inside the muscle fiber.

The team argues that their novel findings indicate that future therapeutic regimes for the treatment of muscle atrophy should focus on intracellular regulatory mechanisms related to protein degradation and synthesis, and not on the regeneration of myonuclei from stem cells. Nevertheless, the team cautions that their findings do not exclude the possibility that myonuclear apoptosis occurs after longer periods of disuse.

References

Bruusgaard, J. C. and Gundersen, K. (2008). In vivo time-lapse microscopy reveals no loss of murine myonuclei during weeks of muscle atrophy. J. Clin. Invest. 118,1450 -1457.[CrossRef][Medline]

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stecyk, J. A. W. Search for Related Content PubMed Articles by Stecyk, J. A. W. Social Bookmarking                         What's this?