Kristian Gundersen

• Afazali, Zabibu; Gundersen, Kristian; Kasozi, Juma; Omala, Saint Kizito & Støve, Bård (2025). Dependence modeling in general insurance using local Gaussian correlations and hidden Markov models. Dependence Modeling. 13(1). doi: 10.1515/demo-2025-0014. Fulltekst i vitenarkiv Vis sammendrag

  Abstract This article introduces a hybrid framework that combines local Gaussian correlation (LGC) with hidden Markov models (HMMs) to model dynamic and nonlinear dependencies in general insurance claims, thereby addressing the limitations of static copula methods. When applied to Kenyan motor insurance claims (2008–2021) and Norwegian home insurance data (2012–2018), the proposed LGC-HMM approach captures regime-specific, nonlinear dependency patterns, revealing distinct stable and crisis periods through structural breaks in the dependency structure. Diagnostic checks confirm the HMM’s ability to reduce residual serial dependence, validating the latent state dynamics. Regime-aware value-at-risk (VaR) and tail VaR estimates derived from the LGC-HMM, using a proposed simulation procedure, outperform static copula models by adapting to structural changes, demonstrating robust forecasting performance. Visualization of forecasts via LGC maps further illustrates evolving tail dependencies. These findings support improved risk diversification and crisis-sensitive pricing strategies in actuarial practice.

• Horwath, Oscar; Cumming, Kristoffer Toldnes; Eftestøl, Einar; Ekblom, Björn; Ackermann, Paul & Raastad, Truls [Vis alle 8 forfattere av denne artikkelen] (2024). No detectable loss of myonuclei from human muscle fibers after 6 wk of immobilization following an Achilles tendon rupture. American Journal of Physiology - Cell Physiology. 328(1), s. C20–C26. doi: 10.1152/ajpcell.00692.2024. Fulltekst i vitenarkiv Vis sammendrag

  Muscle disuse has rapid and debilitating effects on muscle mass and overall health, making it an important issue from both scientific and clinical perspectives. However, the myocellular adaptations to muscle disuse are not yet fully understood, particularly those related to the myonuclear permanence hypothesis. Therefore, in this study, we assessed fiber size, number of myonuclei, satellite cells, and capillaries in human gastrocnemius muscle after a period of immobilization following an Achilles tendon rupture. Six physically active patients (5 males/1 female, 43 ± 15 yr) were recruited to participate after sustaining an acute unilateral Achilles tendon rupture. Muscle biopsies were obtained from the lateral part of the gastrocnemius before and after 6 wk of immobilization using a plaster cast and orthosis. Muscle fiber characteristics were analyzed in tissue cross-sections and isolated single fibers using immunofluorescence and high-resolution microscopy. Immobilization did not change muscle fiber type composition nor cross-sectional area of type I or type II fibers, but muscle fiber volume tended to decline by 13% (P = 0.077). After immobilization, the volume per myonucleus was significantly reduced by 20% (P = 0.008). Myonuclei were not lost in response to immobilization but tended to increase in single fibers and type II fibers. No significant changes were observed for satellite cells or capillaries. Myonuclei were not lost in the gastrocnemius muscle after a prolonged period of immobilization, which may provide support to the myonuclear permanence hypothesis in human muscle. Capillaries remained stable throughout the immobilization period, whereas the response was variable for satellite cells, particularly in type II fibers.

• Schwartz, Lawrence M. & Gundersen, Kristian (2022). Cross Talk opposing view: Myonuclei do not undergo apoptosis during skeletal muscle atrophy. Journal of Physiology. ISSN 0022-3751. 600(9), s. 2081–2084. doi: 10.1113/JP282381. Fulltekst i vitenarkiv
• Melsom, Helene Støle; Heiestad, Christina Mathisen; Eftestøl, Einar; Torp, May-Kristin; Gundersen, Kristian & Bjørnebekk, Astrid [Vis alle 9 forfattere av denne artikkelen] (2022). Reduced arterial elasticity after anabolic–androgenic steroid use in young adult males and mice. Scientific Reports. 12(1). doi: 10.1038/s41598-022-14065-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract High-doses of anabolic–androgenic steroids (AAS) is efficient for building muscle mass, but pose a risk of cardiovascular side effects. Little is known of the effect of AAS on vasculature, but previous findings suggest unfavorable alterations in vessel walls and vasoreactivity. Here, long-term effect of AAS on vascular function and morphology were examined in male weightlifters, and in a mimicking animal model. Arterial elasticity and morphology were tested with ultrasound, pulse wave velocity (PWV) and carotid intima media thickness (cIMT) in 56 current male AAS users, and 67 non-exposed weightlifting controls (WLC). Female mice were treated with testosterone for 14 days and echocardiography were applied to evaluate vascular function and morphology. Male AAS users had higher PWV (p = 0.044), reduced carotid artery compliance (p = 0.0005), and increased cIMT (p = 0.041) compared to WLC. Similar functional changes were found in the ascending aorta of mice after 7- (p = 0.043) and 14 days (p = 0.001) of testosterone treatment. This animal model can be used to map molecular mechanisms responsible for complications related to AAS misuse. Considering the age-independent stiffening of major arteries and the predictive power of an increase in PWV and cIMT, the long-term users of AAS are at increased risk of severe cardiovascular events.

• Eftestøl, Einar; Ochi, Eisuke; Juvkam, Inga; Hansson, Kenth-Arne & Gundersen, Kristian (2022). A juvenile climbing exercise establishes a muscle memory boosting the effects of exercise in adult rats. Acta Physiologica. ISSN 1748-1708. 236(3). doi: 10.1111/apha.13879. Fulltekst i vitenarkiv
• Eftestøl, Einar; Ochi, Eisuke; Juvkam, Inga & Gundersen, Kristian (2021). A juvenile climbing exercise establishes a muscle memory boosting the effects of exercise in adult rats. BioRxiv. ISSN 0362-4331. s. 1–18. doi: 10.1101/2021.06.02.446793. Fulltekst i vitenarkiv
• Bengtsen, Mads; Winje, Ivan Myhre; Eftestøl, Einar; Landskron, Johannes; Sun, Chengyi & Nygård, Kamilla Børve [Vis alle 10 forfattere av denne artikkelen] (2021). Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle. PLoS Genetics. ISSN 1553-7390. 17:e1009907(11). doi: 10.1371/journal.pgen.1009907. Fulltekst i vitenarkiv Vis sammendrag

  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 the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where up to 60% of the nuclei can be of a different origin. Since cellular homogeneity is critical in epigenome-wide association studies we developed 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 labelling and a magnetic-assisted sorting approach, we were able to sort out myonuclei with 95% purity in muscles from mice, rats and humans. The sorting eliminated influence from the 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 differences in the functional properties of the two muscles, and revealed distinct regulatory programs involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles were 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 SIX1 binding sites were found to be overrepresented. In addition, more novel transcription factors for muscle regulation such as members of the MAF family, ZFX and ZBTB14 were identified.

• Hansson, Kenth-Arne; Eftestøl, Einar; Bruusgaard, Jo C.; Juvkam, Inga; Cramer, Alyssa W. & Malthe-Sørenssen, Anders [Vis alle 8 forfattere av denne artikkelen] (2020). Myonuclear content regulates cell size with similar scaling properties in mice and humans. Nature Communications. 11(1). doi: 10.1038/s41467-020-20057-8. Fulltekst i vitenarkiv Vis sammendrag

  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 < 1), making larger cells even more DNA scarce. N scales linearly to cell surface in adult humans, in adult and developing mice, and in mice with genetically reduced N, but in the latter the relationship eventually fails when they reach adulthood with extremely large myonuclear domains. Another exception is denervation-atrophy where nuclei are not eliminated. In conclusion, scaling exponents are remarkably similar across species, developmental stages and experimental conditions, suggesting an underlying scaling law where DNA-content functions as a limiter of muscle cell size.

• Cramer, Alyssa A. W.; Prasad, Vikram; Eftestøl, Einar; Song, Taejeong; Hansson, Kenth-Arne & Dugdale, Hannah F. [Vis alle 10 forfattere av denne artikkelen] (2020). Nuclear numbers in syncytial muscle fibers promote size but limit the development of larger myonuclear domains. Nature Communications. 11, s. 1–14. doi: 10.1038/s41467-020-20058-7. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Mammalian cells exhibit remarkable diversity in cell size, but the factors that regulate establishment and maintenance of these sizes remain poorly understood. This is especially true for skeletal muscle, comprised of syncytial myofibers that each accrue hundreds of nuclei during development. Here, we directly explore the assumed causal relationship between multinucleation and establishment of normal size through titration of myonuclear numbers during mouse neonatal development. Three independent mouse models, where myonuclear numbers were reduced by 75, 55, or 25%, led to the discovery that myonuclei possess a reserve capacity to support larger functional cytoplasmic volumes in developing myofibers. Surprisingly, the results revealed an inverse relationship between nuclei numbers and reserve capacity. We propose that as myonuclear numbers increase, the range of transcriptional return on a per nuclear basis in myofibers diminishes, which accounts for both the absolute reliance developing myofibers have on nuclear accrual to establish size, and the limits of adaptability in adult skeletal muscle.

• Hansson, Kenth-Arne; Solbrå, Andreas Våvang; Gundersen, Kristian & Bruusgaard, Jo C. (2020). Computational assessment of transport distances in living skeletal muscle fibers studied in situ. Biophysical Journal. ISSN 0006-3495. 119(11), s. 2166–2178. doi: 10.1016/j.bpj.2020.10.016. Fulltekst i vitenarkiv
• Psilander, Niklas; Eftestøl, Einar; Cumming, Kristoffer Toldnes; Solgård, Inga Juvkam; Ekblom, Maria M. & Sunding, Kerstin [Vis alle 12 forfattere av denne artikkelen] (2019). Effects of training, detraining, and retraining on strength, hypertrophy, and myonuclear number in human skeletal muscle. Journal of applied physiology. ISSN 8750-7587. 126(6), s. 1636–1645. doi: 10.1152/japplphysiol.00917.2018. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Gundersen, Kristian; Bruusgaard, Jo C.; Egner, Ingrid Marie; Eftestøl, Einar & Bengtsen, Mads (2018). Muscle memory: virtues of your youth? Journal of Physiology. ISSN 0022-3751. 596(18), s. 4289–4290. doi: 10.1113/JP276354. Fulltekst i vitenarkiv
• Winje, Ivan; Sheng, Xia; Hansson, Kenth-Arne; Solbrå, Andreas Våvang; Tennøe, Simen & Saatcioglu, Fahri [Vis alle 8 forfattere av denne artikkelen] (2018). Cachexia does not induce loss of myonuclei or muscle fibres during xenografted prostate cancer in mice. Acta Physiologica. ISSN 1748-1708. s. 1–9. doi: 10.1111/apha.13204. Fulltekst i vitenarkiv
• Winje, Ivan; Bengtsen, Mads; Eftestøl, Einar; Juvkam, Inga; Bruusgaard, Jo C. & Gundersen, Kristian (2018). Specific labelling of myonuclei by an antibody against pericentriolar material 1 on skeletal muscle tissue sections. Acta Physiologica. ISSN 1748-1708. 223(4), s. 1–9. doi: 10.1111/apha.13034. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Gundersen, Kristian (2016). Muscle memory and a new cellular model for muscle atrophy and hypertrophy. Journal of Experimental Biology. ISSN 0022-0949. 219(2), s. 235–242. doi: 10.1242/jeb.124495. Fulltekst i vitenarkiv
• Egner, Ingrid Marie; Bruusgaard, Jo C. & Gundersen, Kristian (2016). Satellite cell depletion prevents fiber hypertrophy in skeletal muscle. Development. ISSN 0950-1991. 143(16), s. 2898–2906. doi: 10.1242/dev.134411. Fulltekst i vitenarkiv
• Eftestøl, Einar; Egner, Ingrid Marie; Lunde, Ida Gjervold; Ellefsen, Stian; Andersen, Tom & Sjåland, Cecilie [Vis alle 8 forfattere av denne artikkelen] (2016). Increased hypertrophic response with increased mechanical load in skeletal muscles receiving identical activity patterns. American Journal of Physiology - Cell Physiology. 311(4), s. C616–C629. doi: 10.1152/ajpcell.00016.2016. Fulltekst i vitenarkiv
• Eftestøl, Einar; Alver, Tine Norman; Gundersen, Kristian & Bruusgaard, Jo C. (2014). Overexpression of SMPX in adult skeletal muscle does not change skeletal muscle fiber type or size. PLOS ONE. 9(6). doi: 10.1371/journal.pone.0099232. Fulltekst i vitenarkiv Vis sammendrag

  Mechanical factors such as stretch are thought to be important in the regulation of muscle phenotype. Small muscle protein X-linked (SMPX) is upregulated by stretch in skeletal muscle and has been suggested to serve both as a transcription factor and a mechanosensor, possibly giving rise to changes in both fiber size and fiber type. We have used in vivo confocal imaging to study the subcellular localization of SMPX in skeletal muscle fibers of adult rats using a SMPX-EGFP fusion protein. The fusion protein was localized predominantly in repetitive double stripes flanking the Z-disc, and was excluded from all nuclei. This localization would be consistent with SMPX being a mechanoreceptor, but not with SMPX playing a role as a transcription factor. In vivo overexpression of ectopic SMPX in skeletal muscle of adult mice gave no significant changes in fiber type distribution or cross sectional area, thus a role of SMPX in regulating muscle phenotype remains unclear.

• Løvås, Tom-Ole; Bruusgaard, Jo C.; Øynebråten, Inger; Gundersen, Kristian & Bogen, Bjarne (2014). DNA vaccines: MHC II-targeted vaccine protein produced by transfected muscle fibres induces a local inflammatory cell infiltrate in mice. PLOS ONE. 9(10). doi: 10.1371/journal.pone.0108069. Fulltekst i vitenarkiv Vis sammendrag

  Vaccination with naked DNA holds great promise but immunogenicity needs to be improved. DNA constructs encoding bivalent proteins that bind antigen-presenting cells (APC) for delivery of antigen have been shown to enhance T and B cell responses and protection in tumour challenge experiments. However, the mechanism for the increased potency remains to be determined. Here we have constructed DNA vaccines that express the fluorescent protein mCherry, a strategy which allowed tracking of vaccine proteins. Transfected muscle fibres in mice were visualized, and their relationship to infiltrating mononuclear cells could be determined. Interestingly, muscle fibers that produced MHC class II-specific dimeric vaccine proteins with mCherry were for weeks surrounded by a localized intense cellular infiltrate composed of CD45+, MHC class II+ and CD11b+ cells. Increasing numbers of eosinophils were observed among the infiltrating cells from day 7 after immunization. The local infiltrate surrounding mCherry+ muscle fibers was dependent on the MHC II-specificity of the vaccine proteins since the control, a non-targeted vaccine protein, failed to induce similar infiltrates. Chemokines measured on day 3 in immunized muscle indicate both a DNA effect and an electroporation effect. No influence of targeting was observed. These results contribute to our understanding for why targeted DNA vaccines have an improved immunogenicity.

• Egner, Ingrid Marie; Bruusgaard, Jo C.; Eftestøl, Einar & Gundersen, Kristian (2013). A cellular memory mechanism aids overload hypertrophy in muscle long after an episodic exposure to anabolic steroids. Journal of Physiology. ISSN 0022-3751. 591(24), s. 6221–6230. doi: 10.1113/jphysiol.2013.264457. Fulltekst i vitenarkiv
• Vikne, Harald; Gundersen, Kristian; Liestøl, Knut; Mæhlen, Jan & Vøllestad, Nina Køpke (2012). Intermuscular relationship of human muscle fiber type proportions: Slow leg muscles predict slow neck muscles. Muscle and Nerve. ISSN 0148-639X. 45(4), s. 527–535. doi: 10.1002/mus.22315. Fulltekst i vitenarkiv
• Bruusgaard, Jo C.; Egner, Ingrid Marie; Klungervik, Tove; Dupre-Aucouturier, S; Desplanches, D & Gundersen, Kristian (2012). No change in myonuclear number during muscle unloading and reloading. Journal of applied physiology. ISSN 8750-7587. 113(2), s. 290–296. doi: 10.1152/japplphysiol.00436.2012. Fulltekst i vitenarkiv
• Gundersen, Kristian (2011). Excitation-transcription coupling in skeletal muscle: the molecular pathways of exercise. Biological Reviews. ISSN 1464-7931. 86(3), s. 564–600. doi: 10.1111/j.1469-185X.2010.00161.x. Fulltekst i vitenarkiv
• Lunde, Ida Gjervold; Anton, Siobhan Lisa; Bruusgaard, Jo C.; Rana, Zaheer Ahmad; Ellefsen, Stian & Gundersen, Kristian (2011). Hypoxia inducible factor 1α links fast-patterned muscle activity and fast muscle phenotype in rats. Journal of Physiology. ISSN 0022-3751. 589(6), s. 1443–1454. doi: 10.1113/jphysiol.2010.202762. Fulltekst i vitenarkiv
• Rana, Zaheer Ahmad; Gundersen, Kristian & Buonanno, Andres (2010). The ups and downs of gene regulation by electrical activity in skeletal muscles. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 30, s. 255–260. doi: 10.1007/s10974-010-9200-2. Fulltekst i vitenarkiv
• Bruusgaard, Jo C.; Johansen, Ida Beitnes; Egner, Ingrid Marie; Rana, Zaheer Ahmad & Gundersen, Kristian (2010). Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 107(34), s. 15111–15116. doi: 10.1073/pnas.0913935107. Fulltekst i vitenarkiv
• Rana, Zaheer Ahmad; Gundersen, Kristian & Buonanno, Andres (2009). The ups and downs of gene regulation by electrical activity in skeletal muscles. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 30(7-8), s. 255–260. doi: 10.1007/s10974-010-9200-2. Fulltekst i vitenarkiv
• Gundersen, Kristian & Bruusgaard, Jo C. (2008). Nuclear domains during muscle atrophy: nuclei lost or paradigm lost? Journal of Physiology. ISSN 0022-3751. 586. doi: 10.1113/jphysiol.2008.154369. Fulltekst i vitenarkiv
• Bruusgaard, Jo C. & Gundersen, Kristian (2008). In vivo time-lapse microscopy reveals no loss of murine myonuclei during weeks of muscle atrophy. Journal of Clinical Investigation. ISSN 0021-9738. 118. doi: 10.1172/JCI34022. Fulltekst i vitenarkiv
• Rana, Zaheer Ahmad; Gundersen, Kristian & Buonanno, Andres (2008). Activity-dependent repression of muscle genes by NFAT. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 105, s. 5921–5926. doi: 10.1073/pnas.0801330105. Fulltekst i vitenarkiv
• Lunde, Ida Gjervold; Ekmark, Merete; Rana, Zaheer Ahmad; Buonanno, Andres & Gundersen, Kristian (2007). PPARdelta expression is influenced by muscle activity and induces slow muscle properties in adult rat muscles after somatic gene transfer. Journal of Physiology. ISSN 0022-3751. 582(3), s. 1277–1287. doi: 10.1113/jphysiol.2007.133025. Fulltekst i vitenarkiv Vis sammendrag

  The effects of exercise on skeletal muscle are mediated by a coupling between muscle electrical activity and gene expression. Several activity correlates, such as intracellular Ca(2+), hypoxia and metabolites like free fatty acids (FFAs), might initiate signalling pathways regulating fibre-type-specific genes. FFAs can be sensed by lipid-dependent transcription factors of the peroxisome proliferator-activated receptor (PPAR) family. We found that the mRNA for the predominant muscle isoform, PPARdelta, was three-fold higher in the slow/oxidative soleus compared to the fast/glycolytic extensor digitorum longus (EDL) muscle. In histological sections of the soleus, the most oxidative fibres display the highest levels of PPARdelta protein. When the soleus muscle was stimulated electrically by a pattern mimicking fast/glycolytic IIb motor units, the mRNA level of PPARdelta was reduced to less than half within 24 h. In the EDL, a three-fold increase was observed after slow type I-like electrical stimulation. When a constitutively active form of PPARdelta was overexpressed for 14 days in normally active adult fibres after somatic gene transfer, the number of I/IIa hybrids in the EDL more than tripled, IIa fibres increased from 14% to 25%, and IIb fibres decreased from 55% to 45%. The level of succinate dehydrogenase activity increased and size decreased, also when compared to normal fibres of the same type. Thus PPARdelta can change myosin heavy chain, oxidative enzymes and size locally in muscle cells in the absence of general exercise. Previous studies on PPARdelta in muscle have been performed in transgenic animals where the transgene has been present during muscle development. Our data suggest that PPARdelta can mediate activity effects acutely in pre-existing adult fibres, and thus is an important link in excitation-transcription coupling.

• Ekmark, Merete; Rana, Zaheer Ahmad; Stewart, G; Hardie, DG & Gundersen, Kristian (2007). De-phosphorylation of MyoD is linking nerve-evoked activity to fast myosin heavy chain expression in rodent adult skeletal muscle. Journal of Physiology. ISSN 0022-3751. 584, s. 637–650. Fulltekst i vitenarkiv
• Bruusgaard, Jo C.; Liestøl, Knut & Gundersen, Kristian (2006). Distribution of myonuclei and microtubules in live muscle fibers of young, middle-aged, and old mice. Journal of applied physiology. ISSN 8750-7587. 100, s. 2024–2030. Fulltekst i vitenarkiv
• Vikne, Harald; Refsnes, PE; Ekmark, Merete; Medbø, Jon Ingulf; Gundersen, Vidar & Gundersen, Kristian (2006). Muscular performance after concentric and eccentric exercise in trained men. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 38(10), s. 1770–1781. Fulltekst i vitenarkiv
• Rana, Zaheer Ahmad; Gundersen, Kristian; Buonanno, A & Vullhorst, D (2005). Imaging transcription in vivo: distinct regulatory effects of fast and slow activity patterns on promoter elements from vertebrate troponin I isoform genes. Journal of Physiology. ISSN 0022-3751. 562. Fulltekst i vitenarkiv
• Bruusgaard, Jo C.; Brack, AS; Hughes, SM & Gundersen, Kristian (2005). Muscle hypertrophy induced by the Ski protein: cyto-architecture and ultrastructure. Acta Physiologica Scandinavica. ISSN 0001-6772. 185(2), s. 141–149. Fulltekst i vitenarkiv
• Gundersen, Kristian (2005). Genteknologi og idrettsprestasjoner. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 125, s. 16–16. Fulltekst i vitenarkiv
• Rana, Zaheer A; Ekmark, Merete & Gundersen, Kristian (2004). Coexpression after electroporation of plasmid mixtures into muscles in vivo. Acta Physiologica Scandinavica. ISSN 0001-6772. 181, s. 233–238. Fulltekst i vitenarkiv
• Bruusgaard, Jo C.; Liestøl, Knut; Ekmark, Merete; Kollstad, K & Gundersen, Kristian (2003). Number and spatial distribution of nuclei in the muscle fibres of normal mice studied in vivo. Journal of Physiology. ISSN 0022-3751. 551(2), s. 467–478. Fulltekst i vitenarkiv
• Ekmark, Merete; Grøvevik, Eirik; Schjerling, Peter & Gundersen, Kristian (2003). Myogenin induces higher oxidative capacity in pre-existing mouse muscle fibres after somatic DNA transfer. Journal of Physiology. ISSN 0022-3751. 548, s. 259–269. Fulltekst i vitenarkiv
• Sollid, Jørund; Angelis, Paula de; Gundersen, Kristian & Nilsson, Gøran Erik (2003). Hypoxia induces adaptive and reversible gross morphological changes in crucian carp gills. Journal of Experimental Biology. ISSN 0022-0949. 206, s. 3667–3673. Fulltekst i vitenarkiv Vis sammendrag

  We show that crucian carp (Carassius carassius) living in normoxic (aerated) water have gills that lack protruding lamellae, the primary site of O2 uptake in fish. Such an unusual trait leads to a very small respiratory surface area. Histological examination showed that the lamellae (secondary lamellae) of these fish were embedded in a cell mass (denoted embedded lamellae). When the fish were kept in hypoxic water, a large reduction in this cell mass occurred, making the lamellae protrude and increasing the respiratory surface area by 7.5-fold. This morphological change was found to be reversible and was caused by increased apoptosis combined with reduced cell proliferation. Carp with protruding lamellae had a higher capacity for oxygen uptake at low oxygen levels than fish with embedded lamellae, but water and ion fluxes appeared to be increased, which indicates increased osmoregulatory costs. This is, to our knowledge, the first demonstration of an adaptive and reversible gross morphological change in the respiratory organ of an adult vertebrate in response to changes in the availability of oxygen.

• Carlsen, Harald & Gundersen, Kristian (2000). Helix-loop-helx transcription factors in electrically active and inactive skeletal muscles. Muscle and Nerve. ISSN 0148-639X. 23, s. 1374–1380. Fulltekst i vitenarkiv
• Utvik, Jo Kristian; Njå, Arild & Gundersen, Kristian (1999). DNA injection into single cells of intact mice. Human Gene Therapy. ISSN 1043-0342. 10, s. 291–300. Fulltekst i vitenarkiv Vis sammendrag

  We describe a technique wherein single muscle fibers of intact mice are made transgenic by intracellular injection of DNA expression vectors for the reporter genes lacZ and green fluorescent protein (GFP). Application of in vivo imaging techniques allowed identification of single cells during the injections, and of the same single cells when the muscle was reexposed days or weeks later. DNA concentration by itself had little effect on fiber survival or expression efficacy, but it seemed crucial to exceed a threshold of about 10(6) injected plasmid molecules in order to obtain expression. On the other hand, experiments with coinjection of two different plasmids suggested that relatively few individual molecules were eventually transcribed in expressing cells. Plasmid DNA remained localized to the injection site, and expression was confined to nuclei in the vicinity. Expression was stable, as reporter was detected 2-61 days after injection.

• Hughes, S.M.; Chi, M.M.Y.; Lowry, O.H. & Gundersen, Kristian (1999). Myogenin induces a shift of enzyme activity from glycolytic to oxidative metabolism in muscles of transgenic mice. Journal of Cell Biology. ISSN 0021-9525. 145(3), s. 633–642. Fulltekst i vitenarkiv
• Windisch, A.; Gundersen, Kristian; Szabolcs, M.J.; Gruber, H. & Lømo, Terje (1998). Fast to slow transformation of denervated and electrically stimulated rat muscle. Journal of Physiology. ISSN 0022-3751. 510(2), s. 623–632. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Gabrielsen, Lin Beate; Gripsrud, Birgitta Haga & Gundersen, Kristian (2025). Ut mot langsom forskning Dagsnytt 18 - NRK Radio. [Radio]. NRK. Fulltekst i vitenarkiv Vis sammendrag

  Fredsprisvinneren, Maria Corina Machado, kommer til Norge, men rakk ikke seremonien i dag.

• Hystad, Joar; Gundersen, Kristian & Gripsrud, Birgitta Haga (2025). Svarer «langsom professor»: — Ikke mulig å drive topp­forskning med norsk arbeids­moral. [Internet]. Khrono. Fulltekst i vitenarkiv Vis sammendrag

  Professor Kristian Gundersen mener at forskning på internasjonalt toppnivå krever langt høyere arbeidsinnsats enn det som er vanlig i Norge.

• Aders, Eirin; Nygård, Kamilla Børve; Bengtsen, Mads & Gundersen, Kristian (2021). Uncovering epigenetic mechanisms behind muscle memory. Fulltekst i vitenarkiv
• Bouzg, M.M.; Dørum, Guro; Gundersen, Kristian; Kohler, Priscila; Hoff-Olsena, P. & Fonneløp, Ane Elida (2021). Erratum to “Is it possible to predict the origin of epithelial cells? – A comparison of secondary transfer of skin epithelial cells versus vaginal mucous membrane cells by direct contact” [Sci. Justice 60 (3) (2020) 234–242] (Science & Justice (2020) 60(3) (234–242), (S1355030619302175), (10.1016/j.scijus.2020.02.003)). Science & justice. ISSN 1355-0306. 61(1), s. 108–108. doi: 10.1016/j.scijus.2020.10.001. Fulltekst i vitenarkiv
• Eftestøl, Einar; Psilander, Niklas; Cumming, Kristoffer Toldnes; Juvkam, Inga; Ekblom, Maria M. & Sunding, Kerstin [Vis alle 12 forfattere av denne artikkelen] (2019). Muscle memory: Are myonuclei ever lost? Journal of applied physiology. ISSN 8750-7587. 128(2), s. 456–457. doi: 10.1152/japplphysiol.00761.2019. Fulltekst i vitenarkiv
• Bengtsen, Mads; Winje, Ivan; Eftestøl, Einar; Domanska, Diana Ewa; Landskron, Johannes & Gundersen, Kristian (2019). The Epigenetic landscape of two phenotypic extreme skeletal muscles - soleus and EDL. Acta Physiologica. ISSN 1748-1708. doi: 10.1111/apha.13414. Fulltekst i vitenarkiv
• Nygård, Kamilla; Juvkam, Inga; Bengtsen, Mads & Gundersen, Kristian (2019). NFATs regulatory potential and role in skeletal muscle during voluntary exercise. Acta Physiologica. ISSN 1748-1708. doi: 10.1111/apha.13414. Fulltekst i vitenarkiv
• Bengtsen, Mads; Winje, Ivan; Landskron, Johannes; Meza-Zepeda, Leonardo A. & Gundersen, Kristian (2019). The Epigenetic landscape of two phenotypic extreme skeletal muscles. Fulltekst i vitenarkiv
• Bengtsen, Mads; Winje, Ivan; Landskron, Johannes; Meza-Zepeda, Leonardi A & Gundersen, Kristian (2019). The Epigenetic landscape of two phenotypic extreme skeletal muscles. Fulltekst i vitenarkiv
• Hansson, Kenth-Arne; Gundersen, Kristian & Bruusgaard, Jo C. (2018). In vivo confocal imaging and 3D rendering of the neuromuscular end plate and its synaptic myonuclei. Acta Physiologica. ISSN 1748-1708. Fulltekst i vitenarkiv
• Bengtsen, Mads; Winje, Ivan; Landskron, Johannes; Meza-Zepeda, Leonardo A. & Gundersen, Kristian (2018). The Epigenetic landscape of two phenotypic extreme skeletal muscles. Fulltekst i vitenarkiv
• Egner, Ingrid Marie; Bruusgaard, Jo C. & Gundersen, Kristian (2017). An apparent lack of effect of satellite cell depletion on hypertrophy could be due to methodological limitations. Response to `Methodological issues limit interpretation of negative effects of satellite cell depletion on adult muscle hypertrophy? Development. ISSN 0950-1991. 144(8), s. 1365–1367. doi: 10.1242/dev.148163. Fulltekst i vitenarkiv
• Eftestøl, Einar; Egner, Ingrid Marie; Ellefsen, Stian; Andersen, Tom; Gundersen, Kristian & Bruusgaard, Jo C. (2016). The importance of mechanosensation in skeletal muscle hypertrophy. Fulltekst i vitenarkiv
• Bruusgaard, Jo C. & Gundersen, Kristian (2014). Musklene dine kan huske. Fulltekst i vitenarkiv
• Eftestøl, Einar; Bruusgaard, Jo C. & Gundersen, Kristian (2012). The contraction duration is not important for hypertrophy in strength trained rats. Fulltekst i vitenarkiv
• Egner, Ingrid Marie; Bruusgaard, Jo C.; Eftestøl, Einar & Gundersen, Kristian (2012). Effects of anabolic steroid on nuclear number and muscle mass. Fulltekst i vitenarkiv
• Anton, Siobhan Lisa; Bruusgaard, Jo C. & Gundersen, Kristian (2011). In vivo knockdown of myogenin leads to a faster muscle phenotype. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 32, s. 345–346. doi: 10.1007/s10974-011-9265-6. Fulltekst i vitenarkiv
• Gundersen, Kristian; Eftestøl, Einar; Egner, Ingrid Marie & Bruusgaard, Jo C. (2011). The effect of testosterone propionate on overloaded skeletal muscle. Fulltekst i vitenarkiv
• Anton, Siobhan Lisa; Bruusgaard, Jo C. & Gundersen, Kristian (2011). In Vivo Knockdown of Myogenin Leads to a Faster Muscle Phenotype. Fulltekst i vitenarkiv
• Anton, Siobhan Lisa; Lunde, Ida Gjervold; Bruusgaard, Jo C. & Gundersen, Kristian (2010). HIF-1a regulates the oxidative capacity of adult rat skeletal muscle. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 32, s. 136–136. doi: 10.1007/s10974-011-9257-6. Fulltekst i vitenarkiv
• Aarebrot, Frank; Waage, Hilde Henriksen; Gundersen, Kristian; Matlary, Janne Haaland; Hessen, Dag Olav & Brochmann, Grete [Vis alle 11 forfattere av denne artikkelen] (2010). Vi er ikke blitt redde! [Journal]. Aftenposten. Fulltekst i vitenarkiv
• Anton, Siobhan Lisa; Lunde, Ida Gjervold; Bruusgaard, Jo C. & Gundersen, Kristian (2010). HIF-1a regulates the oxidative capacity of adult rat skeletal muscle. Fulltekst i vitenarkiv
• Hansen, Einar Eftestøl Holm; Bruusgaard, Jo C. & Gundersen, Kristian (2009). What is the role of SMPX in skeletal muscle? Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 129(1), s. 329–329. Fulltekst i vitenarkiv
• Bruusgaard, Jo C.; Johansen, Ida Beitnes; Egner, Ingrid Marie & Gundersen, Kristian (2009). Are myonuclei forever? Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 30(1), s. 307–307. Fulltekst i vitenarkiv
• Lunde, Ida Gjervold; Bruusgaard, Jo C. & Gundersen, Kristian (2009). HIF-1a regulates fast MyHC expression in skeletal muscle of normally active adult rats. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 129(1), s. 328–328. Fulltekst i vitenarkiv
• Brandtzæg, Per; Bruusgaard, Jo C. & Gundersen, Kristian (2009). Djevelens advokat i Snåsa. Morgenbladet. ISSN 0805-3847. Fulltekst i vitenarkiv
• Brandtzæg, Per; Bruusgaard, Jo C. & Gundersen, Kristian (2009). Lemfeldig observasjon. Morgenbladet. ISSN 0805-3847. Fulltekst i vitenarkiv
• Gundersen, Kristian (2009). Vivant professores? Fulltekst i vitenarkiv
• Gundersen, Kristian (2009). Myter om formidling. Fulltekst i vitenarkiv
• Gundersen, Kristian (2009). Snåsakoden. Fulltekst i vitenarkiv
• Brandtzæg, Per; Bruusgaard, Jo C. & Gundersen, Kristian (2008). Tvilsom bevisvurdering. Morgenbladet. ISSN 0805-3847. Fulltekst i vitenarkiv
• Gundersen, Kristian (2008). Fra akademisk drift til akademisk flom. Fulltekst i vitenarkiv
• Gundersen, Kristian (2007). Etter kunnskapsfallet: Hva nå? 31/8. Fulltekst i vitenarkiv
• Gundersen, Kristian (2007). Frihet under press. 9/6. Fulltekst i vitenarkiv
• Bruusgaard, Jo C. & Gundersen, Kristian (2007). No loss of myonuclei after inactivity-induced skeletal muscle atrophy. Acta Physiologica Scandinavica. ISSN 0001-6772. Fulltekst i vitenarkiv Vis sammendrag

  OBJECTIVE: The skeletal muscle cells are the largest cells in the mammalian body, and are one of few syncytia in mammals. Both in man and in animals it has been widely accepted that muscle cell size is correlated, and perhaps even causally related, to the number of myonuclei. Thus, it is assumed that hypertrophy involves incorporation of new nuclei from satellite cells, and that atrophy involves loss of nuclei by apoptosis. METHODS: Mice were denervated or neural transmission was blocked using TTX for up to 24 days, and stained in vivo using either intracellular injection of fluorescent oligonucleotides, or transfection with a plasmid encoding EGFP with a nuclear localization signal. Apoptotic nuclei were detected using TdT-labeling of fragmented DNA. RESULTS: After denervation up to 24 days there was no loss of myonuclei in neither the EDL nor solei muscles. We found the number of myonuclei per mm to be 52.95±1.7 (before denervation), vs. 54.31±2,8 (after denervation) in the EDL, and in the soleus 71.94±2.9 vs. 74.56±3.9, in spite of a reduction in cross sectional area of more than 50%. TTX block of the sciatic nerve yielded similar results. Apoptotic nuclei were found in the atrophying muscle tissue, but none of these were identified as belonging to muscle fibers. CONCLUSION: The classical idea of a constant karyoplasmatic ratio cannot be maintained for denervation atrophy. We confirm that in the first period after denervation, muscle tissue is undergoing atrophy and an active period of apoptosis, but the loss of cell nuclei by apoptosis seems to be confined to stroma and satellite cells.

• Welde, Boye; Svebak, Sven; Gundersen, Kristian & Ekmark, Merete (2007). Effects of resistance training on muscle histology and cross-country ski performance. Fulltekst i vitenarkiv Vis sammendrag

  Previous research has demonstrated that heavy resistance exercise can increase the endurance performance in runners (Paavolainen et al., 1999) and that upper body training can induce the same effect in cross-country skiers (Hoff et al., 2002, 1999; Østerås et al., 2002; Terzis et al., 2005). It has also been demonstrated that such training improves work economy in runners (Johnston et al., 1997; Paavolainen et al., 1999) and in cross-country skiers (Hoff et al., 2002, 1999; Østerås et al., 2002). Although some previous studies have pointed out the effects of strength and upper body training upon endurance per¬formance, others have found no effect (Bishop et al., 1999; Bastiaans et al., 2001). Moreover, Hoff and co-workers (1999, 2002) and Østerås et al. (2002) studied the effect of maximal resistance exercise in a modified cable pulley specifically designed to simulate the movement pattern of the arms in ski double poling, whereas training outcomes were tested in double poling on a ski-ergometer in the laboratory. Thus, it remains to examine to what extent the findings reported by Hoff and co-workers (1999, 2002) and Østerås et al. (2002) apply to cross-country ski performance. Human skeletal muscles are composed of functionally diverse fibre types and show consider¬able plasticity. They can alter their phenotypic profile as well as significantly in¬crease muscle strength and size in response to specific training stimuli (Pette & Staron, 2001). Although histological and histochemical alterations are well documented in sedentary or moderately trained individuals subjected to concurrent strength and endurance training (Campos et al., 2002; Häkkinen et al., 2003; Putman et al., 2004), less is known about the consequences of adding strength training to already well trained elite endurance athletes. This study aimed at evaluating effects of two intensive resistance exercise programs and to relate these effects to cross-country ski race performance, roller- ski test performance and adaptations of the vastus lateralis muscle in male and female elite junior cross-country skiers. Generally, improvements in roller board test performance positively predicted enhanced roller-ski time-trial test performance (P = 0.04), whereas enhanced performance in push- ups (P = 0.004) and increased cross- sectional area of the type IIAX muscle fibres (P = 0.03) positively predicted cross- country ski race performance. Gender differences in predictions of cross-country ski race performance were observed: Training by 3&#8729;30 reps predicted performance improvement among females (P = 0.05), whereas training by 3&#8729;6 reps predicted performance improvement among males (P = 0.03). Effects of upper body resistance training generally appeared to be important for cross-country ski race performance. Strength test performance rose from pre-to- post training measurements in all subjects. Minor changes were found in vastus lateralis muscle fibre type composition.

• Lunde, Ida Gjervold; Ekmark, Merete; Rana, Zaheer Ahmad; Buonanno, Andres & Gundersen, Kristian (2007). PPARdelta expression differs in slow and fast skeletal muscle and is influenced by muscle activity. Journal of Muscle Research & Cell Motility. 28(7-8), s. 475–475. Fulltekst i vitenarkiv
• Lunde, Ida Gjervold; Ekmark, Merete; Rana, Zaheer Ahmad; Buonanno, Andres & Gundersen, Kristian (2007). PPARdelta is a link between muscle activity and a slow/oxidative muscle phenotype. Acta Physiologica. ISSN 1748-1708. 190, s. 65–65. Fulltekst i vitenarkiv
• Ekmark, Merete & Gundersen, Kristian (2006). MyoD is activity dependent and can change muscle phenotype in the fast direction. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 27(5-7), s. 515–515. Fulltekst i vitenarkiv
• Bruusgaard, Jo C. & Gundersen, Kristian (2006). Muscle atrophy is not accompanied by loss of myonuclei. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 27(5-7), s. 533–533. Fulltekst i vitenarkiv
• Lunde, Ida Gjervold; Ekmark, Merete & Gundersen, Kristian (2006). Regulation of adult muscle phenotype by PPARδ. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 27(5-7), s. 520–520. Fulltekst i vitenarkiv
• Gundersen, Kristian (2006). Motstandere av akademisk frihet. Fulltekst i vitenarkiv
• Gundersen, Kristian (2005). UiOs rolle i Norge: Elitisme på Norsk. Fulltekst i vitenarkiv
• Gundersen, Kristian (2005). Forskeren og revisoren. Fulltekst i vitenarkiv
• Bruusgaard, Jo C.; Brack, Andrew; Hughes, Simon & Gundersen, Kristian (2004). Ultrastrucural changes in young mice expressing the MSVski proto-oncogene. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 25, s. 268–268. Fulltekst i vitenarkiv Vis sammendrag

  Mice carrying the MSVski proto-oncogene undergo muscle hypertrophy. This effect has been attributed to decreased protein breakdown possibly as a result of TGF-b signaling. The muscle fibers of these animals exhibit a reduced specific force (N/mm2) when compared to normal animals. This led us to investigate the ultrastructure of young ski mice using electron microscopy, in order to expose whether there might be a reduction in the relative amount of contractile apparatus. We also used in vivo injections of myonuclear dyes to investigate nuclear number. The study revealed enlarged mitochondria with disintegrated or damaged cristae, disrupted z-discs and a significantly larger amount of non-contractile area. The increase in nuclear number accompanying hypertrophy seen in normal mice was also absent. These findings could explain the lower specific force, as well as indicating a non-myosin related effect of the ski protein.

• Ekmark, Merete & Gundersen, Kristian (2004). Myogenin and MyoD as regulators of muscle phenotype in the adult. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 25(3), s. 272–272. Fulltekst i vitenarkiv
• Ekmark, Merete & Gundersen, Kristian (2003). MyoD -A regulator of fast myosin heavy chains? Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 24(4-6), s. 326–326. Fulltekst i vitenarkiv
• Bruusgaard, Jo C.; Liestøl, Knut; Ekmark, Merete; Kollstad, Kjetil & Gundersen, Kristian (2003). Number and spatial distribution of nuclei in muscle fibers of normal mice studied in vivo. Journal of Muscle Research and Cell Motility. ISSN 0142-4319. 24, s. 326–326. Fulltekst i vitenarkiv
• Gundersen, Kristian (2003). Fristilte universiteter betyr ikke økt akademisk frihet. Fulltekst i vitenarkiv
• Gundersen, Kristian (2000). En ny forskningspolitikk for Norge? Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116. Fulltekst i vitenarkiv
• Gundersen, Kristian; Utvik, Jo Kristian & Njå, Arild (1998). DNA injection in single cells of intact mice. Fulltekst i vitenarkiv
• Gundersen, Kristian; Utvik, Jo Kristian & Njå, Arild (1998). Single transgenic muscle fibers in intact mice. Fulltekst i vitenarkiv
• Ekmark, Merete & Gundersen, Kristian (2007). Transcription factors linking muscle activity to muscle phenotype: A study of myogenin, MyoD and PPARd. Universitetet i Oslo. Fulltekst i vitenarkiv
• Bruusgaard, Jo C. & Gundersen, Kristian (2005). Number and spatial distribution of myonuclei studied in vivo. Universitetet i Oslo. Fulltekst i vitenarkiv
• Ekmark, Merete & Gundersen, Kristian (2002). Effekter av myogenin på skjelettmuskelfibre hos voksne mus. Universitetet i Oslo. Fulltekst i vitenarkiv

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