Effect of Chronic Muscle Denervation on Mitochondrial Biogenesis and Apoptosis
Bibliographic record
Abstract
1825 Chronic muscle disuse, such as that produced by denervation, reduces mitochondrial content and produces muscle atrophy. These changes in muscle phenotype could be provoked by alterations in important regulators of mitochondrial biogenesis, such as the nuclear coactivator PGC-1α, and by increases in muscle fiber cell death via apoptosis. However, the role of PGC-1α following denervation has not been defined, and limited research has assessed apoptotic mechanisms as contributing factors to denervation-induced muscle atrophy. PURPOSE: To assess time-dependent alterations in key proteins involved in mitochondrial biogenesis (PGC-1α, cytochrome c, Tfam, cytochrome oxidase (COX) activity) and apoptosis (HSP70, Bcl-2, BAX, AIF) following chronic muscle denervation. METHODS: Male Sprague-Dawley rats (n = 20) underwent unilateral denervation (DEN) of the sciatic nerve for 5, 21, or 42 days (n = 3–4 animals/day). Denervated and contralateral (control) red gastrocnemius muscles were used for biochemical analyses. RESULTS: Denervation decreased PGC-1α expression by 45% following 5 days of DEN, which was further decreased by 51% and 65% of control at 21 and 42 days, respectively. COX activity declined with time and matched PGC-1α expression, with decreases of 35%, 55%, and 70% at 5, 21, and 42 days of DEN. These changes occurred coincident with 45% decreases in both Tfam and cytochrome c expression at 42 days of DEN. In contrast, proapoptotic BAX expression was elevated by 88% and 115% after 21 and 42 days of DEN, while coincident decreases of 79% and 89% occurred for the expression of the antiapoptotic protein Bcl-2. These changes dramatically increased the BAX:Bcl-2 ratio in denervated muscle. An increase in this ratio is indicative of a greater susceptibility to apoptosis. Additionally, 42 days of DEN resulted in increased (2.0-fold) expression of pro-apoptotic AIF, as well as increased levels (2.9-fold) of anti-apoptotic HSP70. CONCLUSIONS: These results indicate PGC-1α could be an important mediator of the decrements in mitochondrial content following periods of chronic muscle disuse. In addition, the profound shift in BAX:Bcl-2 ratio suggests that denervated muscle has a greater susceptibility to apoptosis and that this likely contributes to denervationinduced atrophy of skeletal muscle. Support: NSERC, Canada.
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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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".