Accelerated Ovarian Failure (AOF) is an Effective Transitional Menopausal Model for the Study of Alzheimer’s Disease
Bibliographic record
Abstract
Abstract Background Biological females account for 70% of Alzheimer’s disease (AD) cases. It’s hypothesized that the estrogen depletion females experience during menopause is a factor in the pathogenesis of AD1. The gold standard rodent model of ovariectomy doesn’t allow for the examination of the gradual loss of estrogen that occurs in humans through perimenopause to menopause2. Administration of 4‐vinylcyclohexene diepoxide (VCD) has emerged as a rodent model of transitional menopause. The goal of this study was to determine how AD and neuronal markers were impacted by the gradual depletion of estrogen in a VCD model of transitional menopause. Method Mature CD1 female mice were injected with VCD (160 mg/kg/d IP for 15 days) to cause gradual ovarian failure over 120 days. A control group was also injected with a vehicle. Sample was collected at four timepoints, two representative of early and late perimenopause (60 and 120 days post injection) while the other two represented early and late menopause (137 and 176 days post injection). At each timepoint, novel object recognition testing (NORT) was performed to assess changes in behavior and memory2. At euthanasia, the prefrontal cortex and hippocampus were collected for protein analysis. Result The NORT demonstrated that the VCD groups at all timepoints had lowered activate memory recall. The prefrontal cortex western blotting results demonstrated that the VCD mice had lower NeuN content across all timepoints. NeuN is a marker of mature neurons which when lowered can have detrimental consequences on memory. SNAP25, a pre‐synaptic protein involved in neuronal synaptic communication, was also lower in the prefrontal cortex of VCD mice across all timepoints. Conclusion The VCD model had impacts on active memory recall which was accompanied by reductions in neuronal and synaptic markers. This indicates that the loss of estrogen through transitional menopause results in early changes in neuronal markers and memory. 1. Iqbal, J. & Zaidi, M. Understanding Estrogen Action during Menopause. Endocrinology 150, 3443‐3445 (2009). 2. Mohammad, A., Finch, M. S., Sweezey‐Munroe, J. & MacPherson, R. E. K. Voluntary wheel running alters markers of amyloid‐beta precursor protein processing in an ovarian hormone depleted model. Front. Endocrinol. 13, 1069404 (2022).
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".