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Gundersen, K.

Publications and source records attributed to Gundersen, K..

3 recordsLinked to original sources

A juvenile climbing exercise establishes a muscle memory boosting the effects of exercise in adult rats

One of the ideas stemming from the discovery of a cellular memory in muscle cells has been that an early exercise period could induce a long-term muscle memory, boosting the effects of exercise later in life. In general muscles are more plastic in younger animals, so we devised a 5-week climbing exercise scheme with food reward administered to juvenile rats (post-natal week 4-9). The juvenile exercise increased fiber cross-sectional area (fCSA), and boosted nuclear accretion. Subsequently the animals were subjected to 10 weeks of detraining (week 9-19, standard caging). During this period fCSA became similar in the animals that had been climbing compared to Naive controls, but the elevated number of myonuclei induced by the climbing were maintained. When the Naive rats were subjected to two weeks of adult exercise (week 19-21) there was little effect on fCSA, while the previously trained rats displayed an increase of 19%. Similarly, when the rats were subjected to unilateral surgical overload in lieu of the adult climbing exercise, the increase in fCSA was 20% (juvenile climbing group) and 11% (Naive rats) compared to the contralateral leg. This demonstrated that juvenile exercise can establish a muscle memory. The juvenile climbing exercise with food reward led to leaner animals with lower body weight. These differences were to some extent maintained throughout the adult detraining period in spite of all animals being fed ad libitum, indicating a form of body weight memory.

physiology↗

The epigenetic landscape in purified myonuclei from fast and slow muscles

Muscle cells have different phenotypes adapted to different usage and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of chromatin environment by ChIP-Seq in two muscle extremes, the almost completely fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where less than 60% of the nuclei are inside muscle fibers. Since cellular homogeneity is critical in epigenome-wide association studies we devised a new method for purifying skeletal muscle nuclei from whole tissue based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labeling and a magnetic-assisted sorting approach we were able to sort out myonuclei with 95% purity. The sorting eliminated influence from other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the functional properties of the two muscles each with a distinct regulatory program involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles are also regulated by different sets of transcription factors; e.g. in soleus binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SOX1 binding sites were found to be overrepresented. In addition, novel factors for muscle regulation such as MAF, ZFX and ZBTB14 were identified.

physiology↗

Computational assessment of transport distances in living skeletal muscle fibers studied in situ

Transport distances in skeletal muscle fibers are mitigated by these cells having multiple nuclei. We have studied mouse living slow (soleus) and fast (extensor digitorum longus) muscle fibers in situ and determined cellular dimensions and the positions of all the nuclei within fiber segments. We modelled the effect of placing nuclei optimally and randomly using the nuclei as the origin of a transportation network. It appeared that an equidistant positioning of nuclei minimizes transport distances along the surface for both muscles. In the soleus muscle however, which were richer in nuclei, positioning of nuclei to reduce transport distances to the cytoplasm were of less importance, and these fibers exhibit a pattern not statistically different from a random positioning of nuclei. Together, these results highlight the importance of spatially distribute nuclei to minimize transport distances to the surface when nuclear density is low, while it appears that the distribution are of less importance at higher nuclear densities.

cell biology↗