Testing the Potential for Nitric Oxide Treatment to Prevent Disuse Atrophy in Muscle During Suspension
Bibliographic record
Abstract
Disuse atrophy in muscle is progressively debilitating in obesity and exacerbates age‐related atrophy. Effective treatment is challenging in both conditions, and prevention is the best approach to avoiding progressive weakness. Since a nitric‐oxide (NO) stimulus activates muscle stem cells, we tested the hypothesis that treatment with a NO‐donor drug, isosorbide dinitrate (ISDN), during hind limb suspension for 18 days, can alleviate muscle atrophy (UM protocol F11‐029). Muscles in unloaded lower and weight‐bearing upper limbs were weighed to study muscle loss. Western blots were used to measure protein levels in experimental (suspended, ISDN‐suspended) and age‐matched control groups of young (3wk) and young‐adult (6–8wk) mice. Protein levels of atrogin‐1, myostatin, and myosin heavy chain isoforms (MyHCs) were analyzed (relative to beta‐actin) for changes expected with muscle atrophy. Analysis of variance was used to determine if changes were statistically significant. Unloaded muscles (quadriceps and soleus) in suspended mice showed atrophy compared to control. In ISDN‐suspended mice, the weight of these 2 muscles tended to increase toward control. In the unloaded quadriceps of suspended mice, ISDN significantly decreased atrogin‐1, a negative regulator of muscle mass (p<0.05) and myostatin precursor, an inhibitor of myogenesis (p<0.05). ISDN also increased the levels of MyHC‐1 and MyHC‐2b in unloaded muscles of suspended young‐adult mice compared to the untreated suspended group. There were no changes in vascular density in quadriceps or pectoralis major as a result of suspension or ISDN treatment, although density was higher in the 6–8 wk than the 3wk group (p<0.05). Suspension resulted in fatty‐liver changes in the 6–8wk group, and ISDN treatment significantly attenuated that increase (p<0.05). Results suggest that NO treatment has the potential to attenuate muscle‐disuse atrophy, with possible significance to preventing atrophy during aging or space travel. Support or Funding Information Supported by the University of Manitoba Research Grant Program (JEA) and NSERC Undergraduate Student Research Award (AZ)
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".