Endogenous cellular prion protein regulates contractility of the mouse ileum
Bibliographic record
Abstract
BACKGROUND: Cellular prion protein (PrP(C) ) is expressed in the enteric nervous system (ENS), however, its physiological role has not been identified. Studies suggest that PrP(C) can function as a metal-binding protein, as absence of the protein has been linked to altered copper metabolism and atypical synaptic activity. Because copper is known to modulate smooth muscle relaxation, we tested the hypothesis that PrP(C) deficiency would alter intestinal contractility. METHODS: We examined electrically evoked ileal contractility in Prnp(-/-) or wild type littermate mice and the effects of copper or copper chelation. PrP(C) expression was studied in whole mount ileal preparations of mice and guinea pigs by immunohistochemistry. KEY RESULTS: Relative to wild type mice, ileal tissues of Prnp(-/-) mice exhibited reduced electrical field stimulation (EFS)-evoked contractility. Furthermore, EFS-induced relaxation, as a percentage of that induced by a nitric oxide donor, was enhanced. Addition of a copper donor to the organ bath increased, whereas the addition of a copper chelator inhibited, nitric oxide donor-induced ileal relaxation in Prnp(-/-) mice. PrP(C) was expressed on nerve fibers or terminals, and some cell bodies in the myenteric and submucosal plexuses of wild type mice. PrP(C) colocalized with a neuron-specific ectonucleotidase, nucleoside triphosphate diphosphohydrolase 3 (NTPDase3), but to only a limited extent with GFAP, a marker of enteric glia. Guinea pigs expressed PrP(C) in nerve fibers or terminals and enteric glia in the myenteric and submucosal plexuses. CONCLUSIONS & INFERENCES: Our findings suggest that PrP(C) , which is abundant in the ENS, has a role in the regulation of ileal contractility.
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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 | 0.000 | 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 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".