Cellular Senescence in Mouse Hippocampus After Irradiation and the Role of p53 and p21
Bibliographic record
Abstract
Diverse stress signals including irradiation may trigger cellular senescence. We asked whether irradiation induced senescence in mouse hippocampus, and whether p53 or p21 played a role in this response. Following whole-brain irradiation, polymerase chain reaction (PCR) arrays for senescence-associated genes showed increased expression of CDKN1A (p21) and CDKN2A (p19ARF) in mouse hippocampus at 9 weeks. Upregulation of p21 and p19ARF was confirmed using real-time PCR, which also demonstrated increased CDKN2A/p16INKa expression after irradiation. No altered regulation of another 17 senescence-associated genes was observed after irradiation. Immunohistochemistry revealed increased nuclear expression of p16INK4A, p19ARF, p53, p21, phosphorylated p38 (pp38), 4-hydroxy-2-nonenal, and interleukin-6 (IL6) in granule cells of dentate gyrus after irradiation. Increased p16 nuclear immunoreactivity was further observed in type -1 cells, the putative neural stem cells. γ-phosphorylated-histone-2A nuclear foci were also seen in dentate gyrus 9 weeks postirradiation. In nonirradiated mice knockout of the TRP53 or p21 gene, there was increased p16INK4A, p19ARF, and IL6, but not pp38 in dentate gyrus. We conclude that irradiation induces transcript and protein expression profile alterations in mouse dentate gyrus consistent with the senescence phenotype. Absence of p53 or p21 results in increase in baseline expression of senescence markers with no further increase in expression after irradiation.
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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) | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| 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".