Melatonin Signaling as a Link between Sleep and Circadian Biology: Practical Implications
Bibliographic record
Abstract
Daniel P. Cardinali UCA-BIOMED-CONICET, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, 1107 Buenos Aires, Argentina Gregory M. Brown Centre for Addiction and Mental Health, University of Toronto, 100 Stokes St., Toronto, ON M6J 1H4, Canada Corresponding author: Dr. Daniel P. Cardinali, UCA-BIOMED-CONICET, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, 1107 Buenos Aires, Argentina. E-mail: danielcardinali@uca.edu.ar, danielcardinali@fibertel.com.ar. Phone: +54911-44743547 ABSTRACT Normal circadian rhythms are synchronized to a regular 24 h environmental light-dark cycle. Both the suprachiasmatic nucleus (SCN) and melatonin are essential for this adaptation. Melatonin exerts its chronophysiological action in part by acting through specific membrane receptors (MT1, MT2), which have been identified in SCN cells as well as in several neural and non-neural tissues. Both receptors have been cloned and share general features with other G protein linked receptors. Melatonin also exerts direct effects on intracellular proteins, such as calmodulin or tubulin, has strong free radical scavenger properties, which are non-receptor mediated, is an effective mitochondrial protector and may interact with proteasome to affect intracellular physiology. Within the SCN, melatonin reduces neuronal activity in a time-dependent manner. The disruption of these circadian mechanisms causes a number of sleep disorders known as circadian rhythm sleep disorders (CRSDs). CRSDs include delayed or advanced sleep phase syndromes; non-24 h sleep-wake rhythm disorder, time zone change syndrome (“jet lag”) and shift work sleep disorder. Disturbances in the circadian phase position of plasma melatonin levels have been found in all these disorders. In addition, comorbidity of severe circadian alterations with neurodegenerative diseases like Alzheimer’s disease (AD) has been documented. Currently there is sufficient evidence to implicate endogenous melatonin as an im- portant mediator in CRSD pathophysiology. The documented efficacy of melatonin to reduce chronic benzodiazepine/Z drug use in insomnia patients is also discussed.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.002 | 0.005 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 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".