Melatonin recovers sleep phase delayed by MK‐801 through the melatonin MT<sub>2</sub> receptor‐ Ca<sup>2+</sup>‐CaMKII‐CREB pathway in the ventrolateral preoptic nucleus
Bibliographic record
Abstract
Abstract Melatonin (MLT) is widely used to treat sleep disorders although the underlying mechanism is still elusive. In mice, using wheel‐running detection, we found that exogenous MLT could completely recover the period length prolonged by N‐methyl‐D‐aspartate receptor (NMDAR) impairment due to the injection of the NMDAR antagonist MK‐801, a preclinical model of psychosis. The analysis of the possible underlying mechanisms indicated that MLT could regulate the homeostatic state in the ventrolateral preoptic nucleus (VLPO) instead of the circadian process in the suprachiasmatic nucleus (SCN). In addition, our data showed that MK‐801 decreased Ca 2+ ‐related CaMKII expression and CREB phosphorylation levels in the VLPO, and MLT could rescue these intracellular impairments but not NMDAR expression levels. Accordingly, Gcamp6 AAV virus was injected in‐vivo to further monitor intracellular Ca 2+ levels in the VLPO, and MLT demonstrated a unique ability to increase Ca 2+ fluorescence compared with MK‐801‐injected mice. Additionally, using the selective melatonin MT 2 receptor antagonist 4‐phenyl‐2‐propionamidotetralin (4P‐PDOT), we discovered that the pharmacological effects of MLT upon NMDAR impairments were mediated by melatonin MT 2 receptors. Using electroencephalography/electromyography (EEG/EMG) recordings, we observed that the latency to the first nonrapid eye movement (NREM) sleep episode was delayed by MK‐801, and MLT was able to recover this delay. In conclusion, exogenous MLT by acting upon melatonin MT 2 receptors rescues sleep phase delayed by NMDAR impairment via increasing intracellular Ca 2+ signaling in the VLPO, suggesting a regulatory role of the neurohormone on the homeostatic system.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.000 | 0.004 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".