Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C042

Oral Communications


E. Eftestøl1,2, I. Juvkam1, E. Ochi2, K. Gundersen1

1. Department of Biosciences, University of Oslo, Oslo, Norway. 2. Hosei University, Kajino, Koganei, Japan.

Previous work from Prof. Kristian Gundersens lab show that myonuclei obtained during hypertrophy are not lost after atrophy, and we hypothesized that these extra myonuclei aid in later muscle re-growth when re-introduced to hypertrophic stimuli (1). This mechanism is dubbed "muscle memory". Briefly, mice received a supraphysiological supplementation of the anabolic-androgenic steroid testosterone propionate (AAS), leading to an increased myonuclear number and muscle growth. After a washout period without AAS, muscle size was back to baseline, but the myonuclear number was still elevated. When subjected to a second hypertrophic stimulus by overloading the lower leg muscles by synergist ablation, muscles previously treated with AAS had a much more pronounced growth than controls without the history of AAS treatment. We hypothesize that the muscle memory mechanism is important also during more physiological relevant training, detraining and retraining. Thus, the aim of the present study was to test the muscle memory hypothesis with a rat climbing model. 4-week-old male Sprague Dawley rats were housed in cages with the inner walls and ceiling covered with a climbing mesh, and the food supply in the middle of the ceiling. Thus, the rats had to climb in order to feed and were thereby trained (1. training). After 5 weeks in the climbing cage, rats were housed in normal cages for 10 weeks (detraining). Age-matched rats in standard cages were used as ground controls. After detraining, both detrained and ground-control rats were subjected to one of two different retraining regimes: 1) 2 weeks in climbing-cages or 2) 2 weeks overload of soleus by synergist tenotomy of gastrocnemius in order to maximize the hypertrophic stimuli and thereby potential differences between experimental groups. Rats were sedated with 2-3% isoflurane in air for the tenotomy and terminal operations. The soleus and tibialis anterior muscles were frozen in melting isopentane in liquid nitrogen, cryosectioned, stained with the myonuclei-specific antibody PCM1 (2), dystrophin antibody to visualize the fiber border and DAPI to visualize all nuclei, followed by analysis of myonuclear number and myofiber cross-sectional area. The 1. training led to an increase in both myonuclear number and myofiber cross-sectional area of both the soleus and tibialis anterior muscles compared to ground-controls. After detraining, cross-sectional area was back to the level of the ground-control, but the myonuclear number was still elevated. Preliminary results indicate that retrained rats had a stronger hypertrophic response compared to age-matched controls performing the training for the first time. Our results support the muscle memory hypothesis under more training-relevant conditions, indicating that an active lifestyle as juvenile might be beneficial for responses to hypertrophic stimuli later in life due to an increased myonuclear number retained in adulthood.

Where applicable, experiments conform with Society ethical requirements