P3‐201: Amyloid‐beta peptide (1‐42) oligomers induce p75NTR expression in hippocampus of mouse brain and SH‐SY5Y human neuroblastoma cells
Bibliographic record
Abstract
p75 neurotrophin receptor (p75) plays a role in the amyloid-ß peptide (Aß) mediated neuronal cell death. We previously reported that p75 expression was upregulated in hippocampus of 3x Tg Alzheimer's disease (AD) mice producing human form of Aß1-42 (Aß1-42) (J Alzheimer's Dis. 2010. 21. 915-26). Aß1-42 also induced p75 expression in SH-SY5Y human neuroblastoma cells. However, induction mechanism remains unknown. Aß oligomer is believed to be predominantly involved in AD pathogenesis. In this study, we investigated the effect of Aß1-42 oligomers on p75 expression in mouse hippocampus and SH-SY5Y cells. Aß-derived diffusible ligands (ADDLs) were prepared by incubation of Aß1-42 at 4C for 24h. ADDLs were microinjected into mouse hippocampus region and 6-24 later hippocampus from ipsilateral and contra lateral sides were analyzed. SH-SY5Y cells were treated with ADDLs in the presence and absence of inhibitor and the effects on p75expression were determined. Western blot analysis showed that ADDLs were heterogeneous mixtures, predominantly made up of Aß1-42 dimers and oligomers. After microinjection of ADDLs into mouse brain, p expression in ipsilateralhippocampus was increased by 1.4-fold in 24hrs compared to contra lateral hippocampus. No significant difference was observed at 6hrs. Anti-Aß antibody (6E10)-positive Aß1-42 was not detected in significant amounts in contralateralhippocampus by immunohistochemistry, suggesting that diffusion into the contralateral side from the injection site is limited. ADDLs (1 uM) increased (1.4-fold) p75 expression in SH-SY5Y cells 24hrs after incubation as previously reported. Insulin-like growth factor I receptor (IGF1R) is reported to be involved in the induction of p expression inSH-SY5Y cells. ADDL-induced p75 expression was inhibited by PPP, a selective IGF1R inhibitor. Moreover, ADDLs induced phosphorylation of IGF1R in SH-SY5Y cells in 30 min. The present study indicates that Aß1-42 oligomersinduce p75 expression in mouse hippocampus and suggests that IGF1Rsignaling pathway contributes to Aß1-42 oligomer-mediated induction of p75 expression in neurons.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".