A53T-α-synuclein overexpression in murine locus coeruleus induces Parkinson’s disease-like pathology in neurons and glia
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Degeneration of noradrenergic locus coeruleus neurons occurs during the prodromal phase of Parkinson's disease and contributes to a variety of non-motor symptoms, e.g. depression, anxiety and REM sleep behavior disorder. This study was designed to establish the first locus coeruleus α-synucleinopathy mouse model, which should provide sufficient information about the time-course of noradrenergic neurodegeneration, replicate cardinal histopathological features of the human Parkinson's disease neuropathology and finally lead to robust histological markers, which are sufficient to assess the pathological changes in a quantitative and qualitative way. We show that targeted viral vector-mediated overexpression of human mutant A53T-α-synuclein in vivo in locus coeruleus neurons of wild-type mice resulted in progressive noradrenergic neurodegeneration over a time frame of 9 weeks. Observed neuronal cell loss was accompanied by progressive α-synuclein phosphorylation, formation of proteinase K-resistant α-synuclein-aggregates, accumulation of Ubi-1- and p62-positive inclusions in microglia and induction of progressive micro- and astrogliosis. Apart from this local pathology, abundant α-synuclein-positive axons were found in locus coeruleus output regions, indicating rapid anterograde axonal transport of A53T-α-synuclein. Taken together, we present the first model of α-synucleinopathy in the murine locus coeruleus, replicating essential morphological features of human Parkinson's disease pathology. This new model may contribute to the research on prodromal Parkinson's disease, in respect to pathophysiology and the development of disease-modifying therapy.
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.
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 | 0.001 | 0.001 |
| 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 it