Distinct behavioural and neurochemical effects of wild type and mutant forms of human alpha-synuclein in mice
Bibliographic record
Abstract
Parkinson's disease (PD)-like behavioural impairments were probed in alpha-synuclein (alpha-syn) transgenic mice in which the Syrian hamster prion (haPrP) promoter controls expression of human wild type (WT) or missense mutant alpha-syn (A53T and A30P) transgenes. We discerned neuromotor performance deficits in adult A53T-Tg and A30P-Tg animals. Fear conditioning and novel object recognition memory tests revealed deficits in A30P-Tg and A53T-Tg animals. Behavioural endophenotypes were accompanied by Tg- and region-specific alterations in constitutive stress-activated protein kinase (SAPK/JNK) activity and by reductions in synaptophysin, a marker of presynaptic vesicles. Catecholamine levels were differentially affected by expression of the Tgs. Although over-expression of WT human alpha-syn can lead to PD in humans, expression of the WT-Tg had no clearly deleterious effects on mice. Our data suggest that haPrP-driven expression of mutant human alpha-syn yields mice with tractable behavioural and neurochemical phenotypes that recapitulate features of human PD.
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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 | 0.001 | 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".