Neuronal to oligodendroglial alpha-synuclein redistribution in a double transgenic model of multiple system atrophy
Bibliographic record
Abstract
Multiple system atrophy is a sporadic, progressive, neurodegenerative disease characterized by an oligodendroglial accumulation of alpha-synuclein (α-syn). The mechanisms underlying the oligodendroglial accumulation of α-syn in the brains of patients with multiple system atrophy have attracted a great deal of interest, given the primarily neuronal role reported for this protein. We examined the interactions between neuronal and oligodendroglial α-syn in the progeny of crosses between parental transgenic (tg) mouse lines that express α-syn either under the oligodendroglial-specific myelin-basic protein promoter (MBP1-hα-syn tg) or under the neuronal platelet-derived growth factor promoter (PDGF-hα-syn tg). Our results demonstrate that progeny from the cross [hα-syn double (dbl) tg mice] displayed a robust redistribution of α-syn accumulation, with a relocalization from a neuronal or a mixed neuronal/oligodendroglial α-syn expression to a more oligodendroglial pattern in both the neocortex and the basal ganglia that closely resembled the parental MBP-hα-syn tg line. The hα-syn dbl tg mice also displayed motor deficits, concomitant with reduced levels of tyrosine hydroxylase and augmented neuropathological alterations in the basal ganglia. These results suggest that the central nervous system milieu in the hα-syn dbl tg mice favors an oligodendroglial accumulation of α-syn. This model represents an important tool to examine the interactions between neuronal and oligodendrocytic α-syn in diseases such as multiple system atrophy.
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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".