Sleep alterations in two different rodent models of Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background In Alzheimer’s disease (AD), sleep alterations are among the first clinical symptoms observed. It is also well‐established that sleep loss affects hippocampal function. Moreover, sleep disturbances enhance the risk of developing AD, but the underlying mechanisms remain unclear. There is mounting literature indicating that soluble low‐molecular‐weight amyloid‐beta oligomers (Aβo) are particularly neurotoxic,1 and their specific contribution to sleep disturbances should be defined. Recently, dysregulation of lipid metabolism was reported in AD and 3xTg‐AD mice,2 but its relation to sleep also need to be assessed. Therefore, our work has two objectives: 1) define the effect of Aβo on different sleep variables and 2) verify whether stearoyl‐coenzyme A desaturase (SCD), an enzyme involved in controlling fatty acid unsaturation, contributes to sleep disturbances in 3xTg‐AD mice. Method Chronic hippocampal injections of soluble Aβo were done in wild‐type male rats, and electroencephalographic (EEG) measurements were performed to define wake/sleep alterations. Additionally, female 3xTg‐AD mice received a 28 day‐treatment with an SCD inhibitor, and EEG recordings were performed either 14 or 28 days post‐treatment Result Results show that the time spent in wakefulness, slow‐wave sleep (SWS) and paradoxical sleep was preserved in Aβo‐injected rats. However, for their frontal cortex, EEG spectral activity during wakefulness was increased by Aβo for slow‐wave activity (SWA; 0.5‐5 Hz) and low‐beta activity (16‐20 Hz), whereas it was decreased during SWS for theta (5‐9 Hz) and alpha activity (9‐12 Hz). Moreover, the theta activity/SWA ratio was decreased during wake and SWS. Concerning 3xTg‐AD mice, they spend more time in SWS during their active period compared to littermates. The number of individual bouts of wake and SWS was increased in 3xTg mice. Ongoing analyses will assess the impact of SCD on sleep variables in 3xTg mice. Conclusion The results support the presence of sleep alterations (indicative of poor sleep quality) in AD models, and suggest that sleep phenotypes could serve as a non‐invasive marker of early AD. 1. Brouillette J, et al. J Neurosci 2012;32:7852‐7861. 2. Hamilton LK, et al. Nat Commun 2022;13:2061.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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".