Prion replication in organotypic brain slice cultures is distinct from in vivo inoculation and is species dependent
Bibliographic record
Abstract
Cultured brain slices rapidly replicate murine prions, exhibit prion pathology, and are amenable towards drug discovery, but have not been infected with human prions. As deer mice (Peromyscus maniculatus) are susceptible to human prions in vivo, here we investigated deer mouse organotypic brain slice cultures as a potential model of human prion disease. Deer mouse brain slices supported replication of rodent-adapted strains of scrapie and Creutzfeldt-Jakob disease (CJD), but they resisted infection with primary human prion inoculum. To better understand this discrepancy, we quantified prion replication rates, characterized cellular and molecular changes, and estimated inoculum clearance within wildtype CD1 and deer mouse brain slice cultures. Prion replication rates varied by species, strain, and brain region, independently of PrP sequence homology. Scrapie-infected CD1 cerebellar slice cultures exhibited the fastest prion replication rate, closely matching in vivo bioassay kinetics and showing neuronal and synaptic degeneration at similar timepoints. However, deer mouse slice cultures replicated deer mouse-adapted sCJD MM1 prions less efficiently than in vivo inoculation. These findings clarify both the utility and constraints of brain slice cultures in modeling prion disease and imply that the slice culture molecular environment may be suboptimal for human prion replication.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".