scholarly journals Dynamic Expression and the Role of BDNF in Exercise-induced Skeletal Muscle Regeneration

2017 ◽  
Vol 38 (13) ◽  
pp. 959-966 ◽  
Author(s):  
Tao Yu ◽  
Yun Chang ◽  
Xiao Gao ◽  
Han Li ◽  
Peng Zhao

AbstractBrain-derived neurotrophic factor (BDNF) is a myokine. However, its role in skeletal muscle has not been well elucidated. In this study, we aimed to investigate its expression profile in skeletal muscle following downhill running and to explore its functions. Male Sprague Dawley rats were assigned to sedentary and downhill running groups. Tail vein blood, total mRNA and protein from soleus muscle was obtained from rats at different time points post-exercise (1d, 3d, 5d, 7d and 14d). We found a significant elevation of BDNF mRNA level 5d and 7d post-exercise (p<0.05), increased BDNF protein level 1d, 3d, 7d and 14d post-exercise (p<0.05), and continuously elevated serum BDNF level (p<0.05). In addition, serum creatine kinase activity was increased 5d following exercise (p<0.05); expression of MyoD was elevated (p<0.05); disruption of myofibers and centralized nuclei in damaged myofibers were clearly observed 1d and 5d post-exercise, respectively. Moreover, AMPK phosphorylation was present 1d post-exercise (p<0.05), while AKT was phosphorylated for 5d post-exercise (p<0.05). In conclusion, downhill running induces a time-dependent up-regulation of BDNF in skeletal muscle, which is involved in exercise-induced skeletal muscle regeneration.

2002 ◽  
Vol 282 (4) ◽  
pp. E802-E809 ◽  
Author(s):  
Stéphanie Duguez ◽  
Léonard Féasson ◽  
Christian Denis ◽  
Damien Freyssenet

Myogenesis requires energy production for the execution of a number of regulatory and biosynthesis events. We hypothesized that mitochondrial biogenesis would be stimulated during skeletal muscle regeneration. Tibialis anterior muscles of male Sprague-Dawley rats were injected with 0.75% bupivacaine and removed at 3, 5, 7, 10, 14, 21, or 35 days after injection ( n = 5–7/group). Two main periods emerged from the histochemical analyses of muscle sections and the expression of proliferating cell nuclear antigen, desmin, and creatine phosphokinase: 1) activation/proliferation of satellite cells ( days 3–14) and 2) differentiation into muscle fibers ( days 5–35). The onset of muscle differentiation was accompanied by a marked stimulation of mitochondrial biogenesis, as indicated by a nearly fivefold increase in citrate synthase activity and state 3 rate of respiration between days 5 and 10. Peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) mRNA level and mitochondrial transcription factor A (mtTFA) protein level peaked on day 10 concurrently with the state 3 rate of respiration. Therefore, transcriptional activation by PGC-1 and mtTFA may be one of the mechanisms regulating mitochondrial biogenesis in regenerating skeletal muscle. Taken together, our results suggest that mitochondrial biogenesis may be an important regulatory event during muscle regeneration.


2021 ◽  
Vol 8 (1) ◽  
pp. 12
Author(s):  
Michael J. McClure ◽  
Lucas C. Olson ◽  
David J. Cohen ◽  
Yen Chen Huang ◽  
Shirley Zhang ◽  
...  

Products developed for skeletal muscle regeneration frequently incorporate allogeneic and xenogeneic materials to elicit a regenerative response to heal skeletal muscle wounds. To avoid graft rejection in preclinical studies, immunodeficient rodents are used. Whether the immunodeficiency alters the host response to the material in skeletal muscle has not been studied. In this study, we hypothesized that an allogeneic acellular skeletal muscle grafts implanted in an immunodeficient rat (RNU, Foxn1-deficient) would exhibit better new muscle fiber formation compared to grafts implanted in immunocompetent Sprague Dawley (SD) rats. Decellularized SD skeletal muscle matrix (DMM) was implanted in the gastrocnemius (N = 8 rats/group). 56 days after surgery, animal gait was examined and animals were euthanized. Muscle force was assessed and fiber number as well as immune cell infiltrate was measured by histomorphometry and immunohistochemistry. Animal gait and percent recovery of muscle force were unchanged in both groups, but newly regenerated muscle fibers increased in RNU rats. Macrophage staining for CD68 was higher in RNU rats than in SD rats. These data show differences in muscle regeneration between animal models using the same biomaterial treatment, but these differences could not be ascribed to the immune response. Overall, our data provide awareness that more studies are needed to understand how host responses to biomaterials differ based on the animal model used.


2021 ◽  
Author(s):  
Quentin Sastourne-Arrey ◽  
Amandine Girousse ◽  
Virginie Bourlier ◽  
Sylvie Monferran ◽  
Marta Gil-Ortega ◽  
...  

Abstract Fibro adipogenic progenitors (FAPs) play a crucial role in skeletal muscle regeneration, as they generate a favorable niche that allows satellite cells to perform efficient muscle regeneration. After muscle injury, FAP content increases rapidly within the injured muscle, the origin of which has been attributed to their proliferation. Recently, single-cell RNAseq approaches have revealed phenotype and functional heterogeneity in FAPs. Here we report that FAP-like cells residing in subcutaneous adipose tissue (ScAT), the adipose stromal cells (ASCs), are rapidly released from ScAT in response to muscle injury. In parallel, we show in healthy humans that exercise-induced muscle stress response triggers the migration of human native ASCs. Additionally, we find that released ASCs infiltrate the damaged muscle, via a platelet dependent mechanism and that blocking ASC infiltration impairs muscle regeneration. Collectively, our data reveal that ScAT is an unsuspected physiological reservoir of regenerative cells that support skeletal muscle regeneration.


2011 ◽  
pp. S147-S154
Author(s):  
D. FILIPOVIĆ ◽  
S. PIRKMAJER ◽  
K. MIS ◽  
T. MARS ◽  
Z. GRUBIC

Many stress conditions are accompanied by skeletal muscle dysfunction and regeneration, which is essentially a recapitulation of the embryonic development. However, regeneration usually occurs under conditions of hypothalamus-pituitary-adrenal gland axis activation and therefore increased glucocorticoid (GC) levels. Glucocorticoid receptor (GR), the main determinant of cellular responsiveness to GCs, exists in two isoforms (GRα and GRβ) in humans. While the role of GRα is well characterized, GRβ remains an elusive player in GC signalling. To elucidate basic characteristics of GC signalling in the regenerating human skeletal muscle we assessed GRα and GRβ expression pattern in cultured human myoblasts and myotubes and their response to 24-hour dexamethasone (DEX) treatment. There was no difference in GRα mRNA and protein expression or DEX-mediated GRα down-regulation in myoblasts and myotubes. GRβ mRNA level was very low in myoblasts and remained unaffected by differentiation and/or DEX. GRβ protein could not be detected. These results indicate that response to GCs is established very early during human skeletal muscle regeneration and that it remains practically unchanged before innervation is established. Very low GRβ mRNA expression and inability to detect GRβ protein suggests that GRβ is not a major player in the early stages of human skeletal muscle regeneration.


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