Soleus and gastrocnemius tenotomy causes fiber type specific muscle atrophy in mouse tibialis anterior
Bibliographic record
Abstract
Examining the molecular mechanisms regulating muscle mass is critical in determining potential therapeutic strategies for preventing muscle loss in a variety of conditions. We have previously utilized a simultaneous muscle overload/unload model, whereby tenotomy of soleus and gastrocnemius tendons mechanically overloads plantaris leading to hypertrophy while unloading soleus leading to atrophy after two weeks. In this model, the foot of the tenotomized leg appears to be held in dorsiflexion, likely due to the loss of soleus and gastrocnemius muscle function, which synergistically act towards plantar flexion. Previous research has shown that dorsiflexion immobilization results in significant muscle atrophy of tibialis anterior (TA) due to an increase in inflammation and polyubiquitylation. Therefore, the present study examined whether TA muscles from the tenotimized leg would also display significant muscle atrophy, and whether increased inflammation and polyubiquitylation would contribute to the muscle loss. We also examined glycogen synthase kinase 3 (GSK3) activation, given this enzyme's role in promoting polyubiquitylation and muscle atrophy. Ten male C57BL/6N mice (28.1 ± 0.8g) were subjected to soleus and gastrocnemius tenotomy (TN) in one leg, while the other leg was subjected to a sham surgery to serve as an internal control (CON). Two‐weeks post‐surgery the mice were euthanized and the TA muscles were collected. On average, TA muscles in the TN leg were smaller compared to the CON leg (CON, 60.0 +/− 2.0 mg vs TNY 52.8 +/− 2.2 mg, p<0.01), suggesting muscle atrophy was occurring in the TN leg. Using immunofluorescent fiber typing, it was found that this was due to a selective reduction in myofiber cross‐sectional area of type IIB (CON 4091± 275 μm 2 vs. TN 3599± 193 μm 2 , p<0.01) and type IIX‐IIB (CON 3281± 243 μm 2 vs. TN 2933± 262 μm 2 , p<0.05), without any significant reductions in total number of myofibers or fiber type distribution. H&E staining showed some centralized nuclei with no signs of mononuclear cell infiltration in the TN TA. Correspondingly, no significant changes in mRNA expression of IL‐6 and TNFa inflammatory cytokines were observed in TN TA. However, we did observe a 1.9‐fold (p<0.05) increase in polyubiquitylated proteins and higher GSK3 activation as revealed by a 30% reduction in phosphorylated GSK3 (relative to total GSK3; p<0.05) in the TN TA compared to CON. In conclusion, TA muscle undergoes a selective atrophy of fast‐glycolytic fibers in response to soleus and gastrocnemius TN, and this may be due to GSK3 activation and polyubiquitylation. Future studies should investigate whether GSK3 represents a viable therapeutic target in this model. Support or Funding Information NSERC This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".