P4–357: Dietary and genetic compromise in folate availability reduces acetylcholine and cognitive performance: Critical role of S–adenosyl methionine
Bibliographic record
Abstract
Folate deficiency has been associated with age–related neurodegeneration. One direct consequence of folate deficiency is a decline in the major methyl donor, S–adenosyl methionine (SAM). Resultant impaired methylation promotes DNA damage and increased presenilin expression (due to impaired DNA methylation), increases oxidative damage (since SAM is an essential cofactor for glutathione–mediated reduction of oxidative species), and fosters accumulation of the neurotoxin homocysteine (since methylation is required for conversion of homocysteine to methionine). We demonstrate herein that dietary folate deficiency in adult mice (9–12 months old) decreased levels of acetylcholine, which were restored by dietary supplementation with SAM even in the absence of folate. Adult mice heterozygously lacking 5',10'–methylene tetrahydrofolate reductase (which are impaired in folate usage and have reduced SAM levels), or homozygously lacking apolipoprotein E (which have reduced SAM due to oxidative stress) and aged (2 – 2.5 year old) normal mice each display reduced acetylcholine levels as compared to normal adult mice. Dietary folate deficiency further reduced acetylcholine, induced cognitive impairment and increased aggression in each of these mice, while supplementation with SAM in the absence of dietary folate restored acetylcholine levels and cognitive performance and reduced aggression to levels observed in the presence of folate. Folate deficiency decreased N–methyl nicotinamine levels, while dietary supplementation with SAM increased methylation of nicotinamide to generate N–methyl nicotinamide. Since N–methyl nicotinamide inhibits choline transport out of the central nervous system, and choline is utilized as an alternative methyl donor, these latter findings suggest that SAM may maintain acetylcholine levels in part by maintaining availability of choline. These findings suggest that dietary supplementation with SAM represents an important therapeutic approach for age–related neurodegeneration.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".