INK4a/ARF Expression Impairs Neurogenesis in the Brain of Irradiated Mice
Bibliographic record
Abstract
Brain neurogenesis is severely impaired following exposure to ionizing radiation (IR). We and others have shown that the expression of the tumor suppressor gene p16INK4a is increased in tissues exposed to IR and thus hypothesized that its expression could limit neurogenesis in the irradiated brain. Here, we found that exposure to IR leads to persistent DNA damage and the expression of p16INK4a in the hippocampus and subventricular zone regions. This was accompanied by a decline in neurogenesis, as determined by doublecortin expression and bromodeoxyuridine incorporation, an effect partially restored in Ink4a/arf-null mice. Increased neurogenesis in the absence of INK4a/ARF expression was independent of apoptosis and activation of the microglia. Moreover, treatment of irradiated mice with a superoxide dismutase mimetic or clearance of p16INK4a-expressing cells using mouse genetics failed to increase neurogenesis. In conclusion, our results suggest that IR-induced p16INK4a expression is a mechanism that limits neurogenesis.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".