Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: 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). We demonstrate herein that pro-oxidant stress and dietary folate deficiency decreased levels of acetylcholine and impaired cognitive performance to various degrees in normal adult mice (9-12 months of age, adult mice heterozygously lacking 5',10'-methylene tetrahydrofolate reductase, homozygously lacking apolipoprotein E, or expressing human ApoE2, E3 or E4, and aged (2-2.5 year old) normal mice. Dietary supplementation with SAM in the absence of folate restored acetylcholine levels and cognitive performance to respective levels observed in the presence of folate. Increased aggressive behavior was observed among some but not all genotypes when maintained on the deficient diet, and was eliminated in all cases supplementation with SAM. Folate deficiency decreased levels of choline and N-methyl nicotinamide, while dietary supplementation with SAM increased methylation of nicotinamide to generate N-methyl nicotinamide and restored choline levels within brain tissue. 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 a useful therapeutic approach for age-related neurodegeneration which may augment pharmacological approaches to maintain acetylcholine levels, in particular during dietary or genetic compromise in folate usage.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".