Amyloid-β-(1-42) Increases Ryanodine Receptor-3 Expression and Function in Neurons of TgCRND8 Mice
Bibliographic record
Abstract
Disruption of intracellular calcium homeostasis precedes the neurodegeneration that occurs in Alzheimer disease (AD). Of the many neuronal calcium-regulating proteins, we focused on endoplasmic reticulum (ER)-resident ryanodine receptors (RyRs) because they are increased in the hippocampus of mice expressing mutant presenilin-1 and are associated with neurotoxicity. Others have observed that ryanodine binding is elevated in human postmortem hippocampal regions suggesting that RyR(s) are involved in AD pathogenesis. Here we report that extracellular amyloid-beta(Abeta)-(1-42) specifically increased RyR-3, but not RyR-1 or RyR-2, gene expression in cortical neurons from C57Bl6 mice. Furthermore, endogenously produced Abeta-(1-42) increased RyR-3 mRNA and protein in cortical neurons from transgenic (Tg)CRND8 mice, a mouse model of AD. Increased RyR-3 mRNA and protein was also observed in brain tissue from 4- to 4.5-month-old Tg animals compared with non-Tg littermate controls. In experiments performed in nominal extracellular calcium, neurons from Tg mice had significant increases in intracellular calcium following ryanodine or glutamate treatment compared with littermate controls, which was abolished by treatment with small interfering RNA directed to RyR-3, indicating that the higher levels of calcium originated from RyR-3-regulated stores. Taken together, these observations suggest that Abeta-(1-42)-mediated changes in intracellular calcium homeostasis is regulated in part through a direct increase of RyR-3 expression and function.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 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".