15 results on '"Jo C. Bruusgaard"'
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2. Computational Assessment of Transport Distances in Living Skeletal Muscle Fibers Studied In Situ
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Jo C. Bruusgaard, Kristian Gundersen, Andreas Våvang Solbrå, and Kenth-Arne Hansson
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In situ ,Multiple nuclei model ,Muscle Fibers, Skeletal ,Biophysics ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Equidistant ,Fiber ,Muscle, Skeletal ,030304 developmental biology ,Cell Nucleus ,Soleus muscle ,0303 health sciences ,Articles ,medicine.anatomical_structure ,Myoglobin ,chemistry ,Cytoplasm ,Muscle Fibers, Fast-Twitch ,Nucleus ,030217 neurology & neurosurgery ,Nuclear density - Abstract
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 modeled 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. We also simulated transport times for myoglobin and found that they were remarkably similar between the two muscles despite differences in nuclear patterning and distances. Together, these results highlight the importance of spatially distributed nuclei to minimize transport distances to the surface when nuclear density is low, whereas it appears that the distribution are of less importance at higher nuclear densities.
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- 2020
3. Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres
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Saleh Omairi, Antonios Matsakas, Hans Degens, Oliver Kretz, Kenth-Arne Hansson, Andreas Våvang Solbrå, Jo C Bruusgaard, Barbara Joch, Roberta Sartori, Natasa Giallourou, Robert Mitchell, Henry Collins-Hooper, Keith Foster, Arja Pasternack, Olli Ritvos, Marco Sandri, Vihang Narkar, Jonathan R Swann, Tobias B Huber, and Ketan Patel
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muscle ,metabolism ,stem cell ,regeneration ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
A central tenet of skeletal muscle biology is the existence of an inverse relationship between the oxidative fibre capacity and its size. However, robustness of this relationship is unknown. We show that superimposition of Estrogen-related receptor gamma (Errγ) on the myostatin (Mtn) mouse null background (Mtn-/-/ErrγTg/+) results in hypertrophic muscle with a high oxidative capacity thus violating the inverse relationship between fibre size and oxidative capacity. We also examined the canonical view that oxidative muscle phenotype positively correlate with Satellite cell number, the resident stem cells of skeletal muscle. Surprisingly, hypertrophic fibres from Mtn-/-/ErrγTg/+ mouse showed satellite cell deficit which unexpectedly did not affect muscle regeneration. These observations 1) challenge the concept of a constraint between fibre size and oxidative capacity and 2) indicate the important role of the microcirculation in the regenerative capacity of a muscle even when satellite cell numbers are reduced.
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- 2016
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4. Long-lasting cellular imprinting: Performance hacking towards the Olympics?
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Einar Eftestøl and Jo C. Bruusgaard
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Long lasting ,Psychology ,Neuroscience ,Imprinting (organizational theory) - Published
- 2021
5. Myonuclear content regulates cell size with similar scaling properties in mice and humans
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Einar Eftestøl, Alyssa W. Cramer, Douglas P. Millay, Inga Juvkam, Anders Malthe-Sørenssen, Kristian Gundersen, Jo C. Bruusgaard, and Kenth-Arne Hansson
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0301 basic medicine ,Adult ,Male ,Cytoplasm ,Intravital Microscopy ,Multiple nuclei model ,Science ,Biopsy ,Cell ,Muscle Fibers, Skeletal ,General Physics and Astronomy ,Skeletal muscle ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell size ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Young Adult ,0302 clinical medicine ,Developmental biology ,medicine ,Myocyte ,Animals ,Humans ,Muscle, Skeletal ,Scaling ,Cell Size ,Cell Nucleus ,Syncytium ,Multidisciplinary ,Microscopy, Confocal ,Chemistry ,General Chemistry ,DNA ,Healthy Volunteers ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Female ,Single-Cell Analysis ,030217 neurology & neurosurgery - Abstract
Muscle fibers are the largest cells in the body, and one of its few syncytia. Individual cell sizes are variable and adaptable, but what governs cell size has been unclear. We find that muscle fibers are DNA scarce compared to other cells, and that the nuclear number (N) adheres to the relationship N = aVb where V is the cytoplasmic volume. N invariably scales sublinearly to V (b, Muscle fibers are the largest cells in the body and contain less DNA per unit volume than other cells even if they have multiple nuclei. Here, the authors show that the number of nuclei regulates the cell size with similar scaling properties in mice and humans.
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- 2020
6. Muscle memory: are myonuclei ever lost?
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Truls Raastad, Kerstin Sunding, Hans-Christer Holmberg, Maria Ekblom, Mathias Wernbom, Einar Eftestøl, Kristian Gundersen, Inga Juvkam, Jo C. Bruusgaard, Kristoffer Toldnes Cumming, Niklas Psilander, and Björn Ekblom
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Physiology ,business.industry ,Physiology (medical) ,Health Sciences ,Muscle Fibers, Skeletal ,Humans ,Medicine ,Hälsovetenskaper ,business ,Neuroscience ,Biomedical sciences ,Muscle memory (strength training) - Published
- 2020
7. Effects of training, detraining, and retraining on strength, hypertrophy, and myonuclear number in human skeletal muscle
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Kerstin Sunding, Inga Juvkam, Jo C. Bruusgaard, Hans-Christer Holmberg, Niklas Psilander, Kristian Gundersen, Truls Raastad, Björn Ekblom, Kristoffer Toldnes Cumming, Einar Eftestøl, Maria Ekblom, and Mathias Wernbom
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0301 basic medicine ,medicine.medical_specialty ,Motor learning ,Physiology ,CSA ,Affect (psychology) ,Muscle hypertrophy ,Myonuclei ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Physiology (medical) ,Health Sciences ,medicine ,Exercise ,biology ,business.industry ,Athletes ,Retraining ,Skeletal muscle ,Hälsovetenskaper ,biology.organism_classification ,Muscle memory (strength training) ,030104 developmental biology ,medicine.anatomical_structure ,business ,Muscle memory ,030217 neurology & neurosurgery ,Biomedical sciences - Abstract
Previously trained mouse muscles acquire strength and volume faster than naïve muscles; it has been suggested that this is related to increased myonuclear density. The present study aimed to determine whether a previously strength-trained leg (mem-leg) would respond better to a period of strength training than a previously untrained leg (con-leg). Nine men and 10 women performed unilateral strength training (T1) for 10 wk, followed by 20 wk of detraining (DT) and a 5-wk bilateral retraining period (T2). Muscle biopsies were taken before and after each training period and analyzed for myonuclear number, fiber volume, and cross-sectional area (CSA). Ultrasound and one repetition of maximum leg extension were performed to determine muscle thickness (MT) and strength. CSA (~17%), MT (~10%), and strength (~20%) increased during T1 in the mem-leg. However, the myonuclear number and fiber volume did not change. MT and CSA returned to baseline values during DT, but strength remained elevated (~60%), supporting previous findings of a long-lasting motor learning effect. MT and strength increased similarly in the mem-leg and con-leg during T2, whereas CSA, fiber volume, and myonuclear number remained unaffected. In conclusion, training response during T2 did not differ between the mem-leg and con-leg. However, this does not discount the existence of human muscle memory, since no increase in the number of myonuclei was detected during T1 and no clear detraining effect was observed for cell size during DT; thus, the present data did not allow for a rigorous test of the muscle memory hypothesis. NEW & NOTEWORTHY If a long-lasting intramuscular memory exists in humans, this will affect strength-training advice for both athletes and the public. Based on animal experiments, we hypothesized that such a memory exists and that it is related to the myonuclear number. However, a period of unilateral strength training, followed by detraining, did not increase the myonuclear number. The training response, during a subsequent bilateral retraining period, was not enhanced in the previously trained leg.
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- 2019
8. Cachexia does not induce loss of myonuclei or muscle fibres during xenografted prostate cancer in mice
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Simen Tennøe, Andreas Våvang Solbrå, Xia Sheng, Ivan Myhre Winje, Kristian Gundersen, Fahri Saatcioglu, Kenth-Arne Hansson, and Jo C. Bruusgaard
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Male ,0301 basic medicine ,medicine.medical_specialty ,Cachexia ,Physiology ,Muscle Fibers, Skeletal ,Transplantation, Heterologous ,Mice, Nude ,030204 cardiovascular system & hematology ,Extensor digitorum longus muscle ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Internal medicine ,Myosin ,medicine ,Animals ,Muscle, Skeletal ,Mice, Inbred BALB C ,Syncytium ,business.industry ,Prostatic Neoplasms ,Skeletal muscle ,musculoskeletal system ,medicine.disease ,Disease Models, Animal ,Muscular Atrophy ,Muscle Fibers, Slow-Twitch ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Muscle Fibers, Fast-Twitch ,Stem cell ,business ,Ex vivo - Abstract
Aim Cachexia is a severe wasting disorder involving loss of body- and muscle mass reducing survival and quality of life in cancer patients. We aim at determining if cachexia is a mere perturbation of the protein balance or if the condition also involves a degenerative loss of myonuclei within the fibre syncytia or loss of whole muscle fibres. Methods We induced cachexia by xenografting PC3 prostate cancer cells in nu/nu mice. Six weeks later, we counted myonuclei by in vivo microscopic imaging of single live fibres in the extensor digitorum longus muscle (EDL), and the EDL, soleus and tibialis anterior muscles were also harvested for ex vivo histology. Results The mice lost on average 15% of the whole-body wt. The muscle wet weight of the glycolytic, fast EDL was reduced by 14%, the tibialis anterior by 17%, and the slow, oxidative soleus by 6%. The fibre cross-sectional area in the EDL was reduced by 21% with no loss of myonuclei or any significant reduction in the number of muscle fibres. TUNEL-positive nuclei or fibres with embryonic myosin were rare both in cachectic and control muscles, and haematoxylin-eosin staining revealed no clear signs of muscle pathology. Conclusion The data suggest that the cachexia induced by xenografted prostate tumours induces a pronounced atrophy not accompanied by a loss of myonuclei or a loss of muscle fibres. Thus, stem cell related treatment might be redundant, and the quest for treatment options should rather focus on intervening with intracellular pathways regulating muscle fibre size.
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- 2018
9. Muscle memory: virtues of your youth?
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Kristian Gundersen, Mads Bengtsen, Einar Eftestøl, Ingrid M. Egner, and Jo C. Bruusgaard
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0301 basic medicine ,medicine.medical_specialty ,Skeletal muscle fibre ,Satellite Cells, Skeletal Muscle ,Physiology ,Muscle Fibers, Skeletal ,Corrections ,DNA, Mitochondrial ,Muscle hypertrophy ,Rats, Sprague-Dawley ,03 medical and health sciences ,Internal medicine ,Physical Conditioning, Animal ,Virtues ,Medicine ,Humans ,Animals ,Muscle Strength ,Cell Nucleus ,Organelle Biogenesis ,business.industry ,Skeletal muscle ,Resistance Training ,Muscle memory (strength training) ,Mitochondria, Muscle ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Female ,business ,Perspectives - Abstract
Referring to the muscle memory theory, previously trained muscles acquire strength and volume much faster than naive muscles. Using extreme experimental models such as synergist ablation or steroid administration, previous studies have demonstrated that the number of nuclei increases when a muscle becomes enlarged, which serves as a cellular muscle memory mechanism for the muscle. In the present study, we found that, when rats were subjected to physiologically relevant resistance training, the number of myonuclei increased and was retained during a long-term detraining period. The acquired myonuclei were related to a greater degree of muscle hypertrophic and mitochondrial biogenesis processes following subsequent hypertrophic conditions. Our data suggest a cellular mechanism supporting the notion that exposing young muscles to resistance training would help to restore age-related muscle loss coupled with mitochondrial dysfunction in later life.Muscle hypertrophy induced by resistance training is accompanied by an increase in the number of myonuclei. The acquired myonuclei are viewed as a cellular component of muscle memory by which muscle enlargement is promoted during a re-training period. In the present study, we investigated the effect of exercise preconditioning on mitochondrial remodelling induced by resistance training. Sprague-Dawley rats were divided into four groups: untrained control, training, pre-training or re-training. The training groups were subjected to weight loaded-ladder climbing exercise training. Myonuclear numbers were significantly greater (up to 20%) in all trained muscles compared to untrained controls. Muscle mass was significantly higher in the re-training group compared to the training group (∼2-fold increase). Mitochondrial content, mitochondrial biogenesis gene expression levels and mitochondrial DNA copy numbers were significantly higher in re-trained muscles compared to the others. Oxidative myofibres (type I) were significantly increased only in the re-trained muscles. Furthermore, in vitro studies using insulin-like growth factor-1-treated L6 rat myotubes demonstrated that myotubes with a higher myonuclear number confer greater expression levels of both mitochondrial and nuclear genes encoding for constitutive and regulatory mitochondrial proteins, which also showed a greater mitochondrial respiratory function. These data suggest that myonuclei acquired from previous training facilitate mitochondrial biogenesis in response to subsequent retraining by (at least in part) enhancing cross-talk between mitochondria and myonuclei in the pre-conditioned myofibres.
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- 2018
10. Deltamethrin resistance in the salmon louse, Lepeophtheirus salmonis (Krøyer): Maternal inheritance and reduced apoptosis
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Marit Jørgensen Bakke, Jo C. Bruusgaard, Arvind Y. M. Sundaram, Tor Einar Horsberg, and Celia Agusti
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0301 basic medicine ,Male ,Non-Mendelian inheritance ,Insecticides ,Drug Resistance ,lcsh:Medicine ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Article ,Arthropod Proteins ,Copepoda ,Electron Transport Complex IV ,03 medical and health sciences ,Fish Diseases ,Salmon louse ,Nitriles ,Pyrethrins ,Cytochrome c oxidase ,Animals ,lcsh:Science ,Gene ,Genetics ,Principal Component Analysis ,Multidisciplinary ,biology ,lcsh:R ,NADH dehydrogenase ,biology.organism_classification ,Mitochondria ,Protein Subunits ,030104 developmental biology ,Lepeophtheirus ,biology.protein ,DNA fragmentation ,lcsh:Q ,Female ,Maternal Inheritance ,Transcriptome - Abstract
Resistance towards deltamethrin (DMT) in the crustacean ectoparasite Lepeophtheirus salmonis (Caligidae) is a problem on fish farms lining the North Atlantic Ocean. Two Norwegian strains with different susceptibility towards DMT were crossed in the parental generation (P0), females from a sensitive strain were crossed with males from a resistant strain and vice versa. Individual susceptibility towards DMT was assessed in the second filial generation (F2). DMT resistance was only found in F2 descendants when the P0 females were from the resistant strain, pointing to maternal inheritance. Since maternal inheritance might be linked to the mitochondrial (mt) genome, the nucleotide sequences and the gene expressions of mt-genes were analysed. Twenty non-synonymous single nucleotide polymorphisms (SNPs) were identified in mt-transcripts from resistant F2 parasites, including SNPs in two cytochrome C oxidase subunits (COX1 and COX3) and two subunits of the NADH dehydrogenase complex (ND1 and ND5) previously linked to DMT resistance in the salmon louse. Differential expression analysis between the sensitive and resistant strain revealed strain effect in seven out of twelve mt-genes. The current study also show that DNA fragmentation (indicating apoptosis) was affected by DMT exposure in skeletal muscle tissue and that resistant parasites undergo less apoptosis than sensitive parasites.
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- 2018
11. Author response: Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres
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Kenth-Arne Hansson, Andreas Våvang Solbrå, Hans Degens, Vihang A. Narkar, Jonathan R. Swann, Antonios Matsakas, Oliver Kretz, Olli Ritvos, Jo C. Bruusgaard, Tobias B. Huber, Ketan Patel, Arja Pasternack, Roberta Sartori, Natasa Giallourou, Keith Foster, Henry Collins-Hooper, Saleh Omairi, Robert Mitchell, Barbara Joch, and Marco Sandri
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Chemistry ,Oxidative phosphorylation ,Cell biology - Published
- 2016
12. Increased hypertrophic response with increased mechanical load in skeletal muscles receiving identical activity patterns
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Ingrid M. Egner, Cecilie Sjåland, Kristian Gundersen, Tom Andersen, Stian Ellefsen, Jo C. Bruusgaard, Ida G. Lunde, and Einar Eftestøl
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0301 basic medicine ,medicine.medical_specialty ,Physiology ,Strength training ,Biology ,Muscle hypertrophy ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Internal medicine ,Isometric Contraction ,medicine ,Animals ,Mechanotransduction ,Muscle, Skeletal ,Mechanical load ,Fiber type ,Ribosomal Protein S6 Kinases ,TOR Serine-Threonine Kinases ,Cell Biology ,Hypertrophy ,Rats ,030104 developmental biology ,Endocrinology ,Myogenin ,Proto-Oncogene Proteins c-akt ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
It is often assumed that mechanical factors are important for effects of exercise on muscle, but during voluntary training and most experimental conditions the effects could solely be attributed to differences in electrical activity, and direct evidence for a mechanosensory pathway has been scarce. We here show that, in rat muscles stimulated in vivo under deep anesthesia with identical electrical activity patterns, isometric contractions induced twofold more hypertrophy than contractions with 50–60% of the isometric force. The number of myonuclei and the RNA levels of myogenin and myogenic regulatory factor 4 were increased with high load, suggesting that activation of satellite cells is mechano dependent. On the other hand, training induced a major shift in fiber type distribution from type 2b to 2x that was load independent, indicating that the electrical signaling rather than mechanosignaling controls fiber type. RAC-α serine/threonine-protein kinase (Akt) and ribosomal protein S6 kinase β-1 (S6K1) were not significantly differentially activated by load, suggesting that the differences in mechanical factors were not important for activating the Akt/mammalian target of rapamycin/S6K1 pathway. The transmembrane molecule syndecan-4 implied in overload hypertrophy in cardiac muscle was not load dependent, suggesting that mechanosignaling in skeletal muscle is different.
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- 2016
13. Satellite cell depletion prevents fiber hypertrophy in skeletal muscle
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Kristian Gundersen, Jo C. Bruusgaard, and Ingrid M. Egner
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0301 basic medicine ,Genetically modified mouse ,Satellite Cells, Skeletal Muscle ,Muscle Fibers, Skeletal ,Mice, Transgenic ,Biology ,Muscle hypertrophy ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,medicine ,Animals ,Muscle, Skeletal ,Molecular Biology ,Cell Nucleus ,Syncytium ,Skeletal muscle ,Anatomy ,Hypertrophy ,musculoskeletal system ,Immunohistochemistry ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Female ,Plantaris muscle ,Stem cell ,030217 neurology & neurosurgery ,Ex vivo ,Developmental Biology - Abstract
The largest mammalian cells are the muscle fibers, and they have multiple nuclei to support their large cytoplasmic volumes. During hypertrophic growth, new myonuclei are recruited from satellite stem cells into the fiber syncytia, but it was recently suggested that such recruitment is not obligatory: overload hypertrophy after synergist ablation of the plantaris muscle appeared normal in transgenic mice in which most of the satellite cells were abolished. When we essentially repeated these experiments analyzing the muscles by immunohistochemistry and in vivo and ex vivo imaging, we found that overload hypertrophy was prevented in the satellite cell-deficient mice, in both the plantaris and the extensor digitorum longus muscles. We attribute the previous findings to a reliance on muscle mass as a proxy for fiber hypertrophy, and to the inclusion of a significant number of regenerating fibers in the analysis. We discuss that there is currently no model in which functional, sustainable hypertrophy has been unequivocally demonstrated in the absence of satellite cells; an exception is re-growth, which can occur using previously recruited myonuclei without addition of new myonuclei.
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- 2015
14. Less than recommended training of aerobic fitness and muscle strength: What to expect?
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Haakon B. Benestad, Jo C. Bruusgaard, and Kristin L. Sand
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medicine.medical_specialty ,Time Factors ,Physiology ,Health Status ,Physical fitness ,High-Intensity Interval Training ,030204 cardiovascular system & hematology ,Running ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Humans ,Medicine ,Aerobic exercise ,Muscle Strength ,Muscle, Skeletal ,Exercise ,business.industry ,030229 sport sciences ,Bicycling ,Physical Fitness ,Muscle strength ,medicine.symptom ,business ,Muscle Contraction ,Muscle contraction - Published
- 2018
15. Specific labelling of myonuclei by an antibody against pericentriolar material 1 on skeletal muscle tissue sections
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Mads Bengtsen, Kristian Gundersen, Jo C. Bruusgaard, Inga Juvkam, Ivan Myhre Winje, and Einar Eftestøl
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Male ,0301 basic medicine ,Cell type ,Physiology ,Cell ,Cell Cycle Proteins ,Autoantigens ,Antibodies ,Muscle hypertrophy ,Rats, Sprague-Dawley ,Mice ,03 medical and health sciences ,0302 clinical medicine ,PCM1 ,Muscular Diseases ,Antibody Specificity ,medicine ,Animals ,Humans ,Muscle, Skeletal ,Pericentriolar material ,Cell Nucleus ,biology ,Skeletal muscle ,Hypertrophy ,musculoskeletal system ,Immunohistochemistry ,Actins ,Cell biology ,Disease Models, Animal ,Luminescent Proteins ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Female ,mCherry ,Dystrophin ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Aim Skeletal muscle is a heterogeneous tissue containing several different cell types, and only about 40%-50% of the cell nuclei within the tissue belong to myofibres. Existing technology, attempting to distinguish myonuclei from other nuclei at the light microscopy level, has led to controversies in our understanding of the basic cell biology of muscle plasticity. This study aims at demonstrating that an antibody against the protein pericentriolar material 1 (PCM1) can be used to reliably identify myonuclei on histological cross sections from humans, mice and rats. Methods Cryosections were labelled with a polyclonal antibody against PCM1. The specificity of the labelling for myonuclei was verified using 3D reconstructions of confocal z-stacks triple-labelled for DNA, dystrophin and PCM1, and by co-localization with nuclear mCherry driven by the muscle-specific Alpha-Actin-1 promoter after viral transduction. Results The PCM1 antibody specifically labelled all myonuclei, and myonuclei only, in cryosections of muscles from rats, mice and men. Nuclei in other cell types including satellite cells were not labelled. Both normal muscles and hypertrophic muscles after synergist ablation were investigated. Conclusion Pericentriolar material 1 can be used as a specific histological marker for myonuclei in skeletal muscle tissue without relying on counterstaining of other structures or cumbersome and subjective analysis of nuclear positioning.
- Published
- 2018
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