Vitamin D <sub>3</sub> supplementation at 50x the adequate intake attenuates disease pathophysiology in the spinal cord of male, but is toxic in female, G93A mouse model of amyotrophic lateral sclerosis (ALS)
Bibliographic record
Abstract
Background Vitamin D3 (D3) at 50x the adequate intake (AI) improves paw grip endurance in G93A mice. However, quadriceps apoptosis increases in females, indicating a threshold of toxicity. ALS is a neuromuscular disease characterized by progressive degeneration of upper and lower motor neurons. Objective We analyzed the spinal cords of G93A mice following dietary D3 supplementation at 50x the AI for oxidative damage (4-HNE, 3-NY), antioxidant enzymes (SOD2, catalase, GPx1), inflammation (TNF-α, IL-6, IL-10), apoptosis (bax/bcl-2 ratio, CASP3 cleaved/pro ratio), neurotrophic factor (GDNF), and neuron count (ChAT, SMI36/32 ratio). Methods: Beginning at age 25 d, 41 G93A mice were provided food ad libitum with either adequate (AI; 1 IU D3/g feed; 12 M, 11 F) or high (HiD; 50 IU D3/g feed; 10 M, 8 F) D3. At age 113 d, the spinal cords were analyzed for protein content. Differences were considered significant at P 蠄 0.05. Results: HiD females had 14% higher 3-NY (P = 0.065), 21% lower catalase (P < 0.0001), 21% higher TNF- α (P = 0.003), 13% lower IL-10 (P = 0.042), 13% higher CASP3 (P = 0.010) and 18% lower ChAT (P = 0.024) vs. AI. HiD males had 16% lower 3-NY (P = 0.073), 24% lower IL-6 (P = 0.085), 26% lower CASP3 (P = 0.009) and 19% lower SMI36/32 (P = 0.098) vs. AI. Conclusion In G93A mice, dietary D3 at 50x AI is toxic in the spinal cord of females but attenuates disease pathophysiology in males. This is in accord with results in the quadriceps, as well as functional and disease severity outcomes. Future studies need to identify the sex-specific therapeutic dose of D3 for ALS. Grant Funding Source: NSERC, Faculty of Health-York U.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".