SEK1/MKK4, c‐Jun and NF<sub>Κ</sub>B are differentially activated in forebrain neurons during postnatal development and injury in both control and p75<sup>NGFR</sup>‐deficient mice
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Bibliographic record
Abstract
The common neurotrophin receptor (p75NGFR) can signal in vitro through activation of the c-Jun N-terminal kinase (JNK) pathway and nuclear translocation of NFKappaB. Activation of JNK and its substrate c-Jun can lead to apoptosis. We investigated these activities in vivo by comparing immunoreactivity for phosphorylated(p) SEK-1 (or MKK4, which activates JNK), c-Jun (ser63, ser73) and nuclear translocation of NFKappaB-p50 in tissue sections through the forebrain of control and p75NGFR-deficient mice. During postnatal development, SEK1p-immunoreactivity was detectable in p75NGFR-positive cholinergic neurons and p75NGFR-negative neurons throughout the forebrain in control mice. During development, few cells contained c-Junp, although many neurons contained c-Jun. No obvious c-Jun immunostaining was present in the adult forebrain. At any age, NFKappaB-p50 immunoreactivity was seen in nuclei of most cells throughout the forebrain. Following fimbria fornix transection in adult mice, few basal forebrain neurons contained SEK1p while many axotomized choline acetyltransferase (ChAT)-positive neurons contained c-Junp and nuclear NFKappaB-p50. The immunostaining patterns of SEK1p, c-Junp and NFKB during development and following injury were largely similar in p75NGFR-deficient mice. During development, cells throughout the forebrain had TdT-mediated dUTP-biotin nick end labelling (TUNEL)-labelling (a potential marker for apoptosis), however, their presence was not predicted by number of neurons stained for SEK1p or c-Junp. These results suggest that the expected activation of the JNK pathway by p75NGFR, as well as the expected relationship between SEK1 and downstream activation of c-Jun do not occur in the mammalian forebrain. Also, these results suggest that this activation does not necessarily lead to cell death.
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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 | 0.000 |
| 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) | 0.000 | 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 it