Neuroprotection and immunomodulation of progesterone in the gut of a mouse model of Parkinson's disease
Bibliographic record
Abstract
Abstract Gastrointestinal symptoms appear in Parkinson's disease patients many years before motor symptoms, suggesting the implication of dopaminergic neurones of the gut myenteric plexus. Inflammation is also known to be increased in PD . We previously reported neuroprotection with progesterone in the brain of mice lesioned with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine ( MPTP ) and hypothesised that it also has neuroprotective and immunomodulatory activities in the gut. To test this hypothesis, we investigated progesterone administered to adult male C57 BL /6 mice for 10 days and treated with MPTP on day 5. In an additional experiment, progesterone was administered for 5 days following MPTP treatment. Ilea were collected on day 10 of treatment and microdissected to isolate the myenteric plexus. Dopaminergic neurones were reduced by approximately 60% and pro‐inflammatory macrophages were increased by approximately 50% in MPTP mice compared to intact controls. These changes were completely prevented by progesterone administered before and after MPTP treatment and were normalised by 8 mg kg ‐1 progesterone administered after MPTP . In the brain of MPTP mice, brain‐derived neurotrophic peptide ( BDNF ) and glial fibrillary acidic protein ( GFAP ) were associated with progesterone neuroprotection. In the myenteric plexus, increased BDNF levels compared to controls were measured in MPTP mice treated with 8 mg kg ‐1 progesterone started post MPTP , whereas GFAP levels remained unchanged. In conclusion, the results obtained in the present study show neuroprotective and anti‐inflammatory effects of progesterone in the myenteric plexus of MPTP mice that are similar to our previous findings in the brain. Progesterone is non‐feminising and could be used for both men and women in the pre‐symptomatic stages of the disease.
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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".