Dietary vitamin D3 supplementation at 50× the adequate intake decreases calbindin d28k and endoplasmic reticulum stress and increases apoptosis, suggesting toxicity, in the female transgenic G93A mouse model of amyotrophic lateral sclerosis
Bibliographic record
Abstract
Background We previously showed that dietary vitamin D 3 (D 3 ) at 50× the adequate intake increased functional capacity in the transgenic G93A mouse model of amyotrophic lateral sclerosis (ALS), with females exhibiting signs of D 3 toxicity. ALS is a progressive neuromuscular disease resulting in the death of upper and lower motor neurons. Objective In this pilot study, we analyzed the quadriceps of G93A mice following dietary D 3 supplementation at 50× the AI for vitamin D receptor and markers of intracellular calcium trafficking (calbindin d28k, calretinin), endoplasmic reticulum (ER) stress (SERCA2, CHOP) and apoptosis (bax/bcl2 ratio, caspase 12 cleaved/pro ratio). Methods Beginning at age 25 d, 41 G93A mice were provided food ad libitum with either adequate (AI; 1 IU D 3 /g feed; 12 M, 11 F) or high (HiD; 50 IU D 3 /g feed; 10 M, 8 F) D 3 . At age 113 d, the quadriceps were analyzed for protein content. Differences were considered significant at P ≤ 0.10. Results In females, HiD had 33% lower calbindin d28k (P = 0.066), 68% lower CHOP (P = 0.074), and 242% higher bax/bcl2 ratio (P = 0.080) vs. AI. HiD males showed no significant differences vs. AI. Conclusion Dietary D 3 at 50× the AI decreases ER stress in the quadriceps of female G93A mice, but increases apoptosis, which could be due to D 3 toxicity. We hypothesize a dynamic crosstalk between ER stress and calcium trafficking. (Supported by NSERC and Faculty of Health, York University) Grant Funding Source : NSERC and Faculty of Health, York University
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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) | 0.002 | 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".