Epigenetic modulation of cognitive function: toward new treatment models
Bibliographic record
Abstract
Abstract Background The current translational work is an outgrowth of a mechanistic framework in rodents with cognitive deficits and depressive‐like traits, wherein the levels of the pivotal mitochondrial metabolite acetyl‐L‐carnitine (LAC) are decreased and signal to the brain abnormal activity of histone acetyltransferase and expression of genes key for neuronal plasticity, such as mGlu2 (a key inhibitor of glutamate release). Yet, the role of this emerging signaling pathway of brain plasticity remains to be fully determined in subjects with cognitive impairments (CI). Method Here we performed ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) to measure peripheral levels of LAC and the related mitochondrial metabolite free‐carnitine in a cohort of subjects with cognitive impairments (CI, n = 29) and age‐ and sex‐matched cognitively healthy controls (HC, n = 32). Next, we performed multiple regression analysis to investigate the relationship between mitochondrial metabolism of LAC and clinical characteristics. Result Decreased levels of the pivotal mitochondrial metabolite LAC in subjects with CI as compared to age‐ and sex‐matched HC subjects (p = 0.02), with potential sex differences in peripheral levels of free‐carnitine (p = 0.03). Incorporation of these new measures into a canonical biomarker model improved diagnostic accuracy Conclusion Our new translational findings suggest that a deficiency of LAC, and potential sex differences in free‐carnitine levels, might define clinical phenotypes of CI. Ongoing studies are ascertaining the role between LAC levels, and its main metabolite free‐carnitine, in relation to specific cognitive domains.
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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 | 0.002 | 0.001 |
| 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 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".