Sex and Age Differences in a Progressive Synucleinopathy Mouse Model
Bibliographic record
Abstract
The mutation and overexpression of the alpha-synuclein protein (αSyn), described as synucleinopathy, is associated with Parkinson's disease (PD)-like pathologies. A higher prevalence of PD is documented for men versus women, suggesting female hormones' implication in slowing PD progression. The nigrostriatal dopamine (DA) neurons in rodent males are more vulnerable to toxins than those in females. The effect of biological sex on synucleinopathy remains poorly described and was investigated using mice knocked out for murine αSyn (SNCA-/-) and also overexpressing human αSyn (SNCA-OVX) compared to wildtype (WT) mice. All the mice showed decreased locomotor activity with age, and more abruptly in the male than in the female SNCA-OVX mice; anxiety-like behavior increased with age. The SNCA-OVX mice had an age-dependent accumulation of αSyn. Older age was associated with the loss of nigral DA neurons and decreased striatal DA contents. The astrogliosis, microgliosis, and cytokine concentrations increased with aging. More abrupt nigrostriatal DA decreases and increased microgliosis were observed in the male SNCA-OVX mice. Human αSyn overexpression and murine αSyn knockout resulted in behavioral dysfunctions, while only human αSyn overexpression was toxic to DA neurons. At 18 months, neuroprotection was lost in the female SNCA-OVX mice, with a likely loss of estrus cycles. In conclusion, sex-dependent αSyn toxicity was observed, affecting the male mice more significantly.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".