P1‐284: Early expression of cyclin D1 in vulnerable brain areas of TgCRND8 mouse model of Alzheimer's disease
Bibliographic record
Abstract
Unscheduled reinitiation of cell cycle in post-mitotic cells (such as neurons) preceds their death in some paradigms of neurodegeneration, including Alzheimer's disease (AD). We used a transgenic TgCRND8 mouse model to explore whether induction of the cell cycle molecule, cylcin D1, may serve as an early marker of AD-associated neuronal death. Cyclin D1 expression was analyzed in soluble protein extracts obtained from vulnerable (cortex and hippocampus) and relatively spared (striatum and cerebellum) brain regions coming from 4, 6 and 9 month-old transgenic mice and wild-type littermates. The cyclin D1 expression was correlated with caspase-3 activation as determined by Western blot quantification using the antibody directed against the active form of this key inductor of apoptotic cell death. We found that in cortex and hippocampus of TgCRND8 mice, levels of cyclin D1 expression is increased (25-30%) over wild-type mice at all ages studied. Interestingly, in hippocampus at 9 months of age, cyclin D1 expression was even greater and reached 2-3 fold higher levels in transgenic than in wild type mice. By contrast, in striatum and cerebellum, cyclin D1 levels in transgenic mice were not increased. The observed increased expression of cyclin D1 in vulnerable brain regions was correlated with increased caspase-3 activation. However, no caspase-3 activation was detected in the hippocampus of 9 months-old TgCRND8 in comparison to the age-matched littermates. In striatum and cerebellum, no activation of caspase-3 was seen in all age groups, in agreement with a general view that in AD, these regions are relatively spared from neuronal death. These data suggest that cyclin D1 may be an early marker of cell death since increased expression correlates with caspase-3 activation in vulnerable, but not in spared brain regions, and occurs at the ages (4 and 6 months) where no major neuronal death is observed in this model (Belluci, Neurobiol Disease 2006; Ramos, Neurobiol Aging, 2006).
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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 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".