Effect of Oestrogen Receptors on Brain NMDA Receptors of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine Mice
Bibliographic record
Abstract
Parkinson's disease (PD) is characterised by the loss of nigrostriatal dopamine (DA) neurones and glutamate overactivity. There is substantial evidence to suggest that oestrogens prevent or delay the disease. 17β-oestradiol has neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and modulates brain NMDA receptors. In MPTP-lesioned mice, oestrogen receptor (ER)α and ERβ are important in 17β-oestradiol-induced neuroprotection. To evaluate the role of ERs in the response of NMDA receptors to lesion, we compared wild-type (WT) with ER knockout (KO) C57Bl/6 male mice that received 7, 9 or 11 mg/kg of MPTP. These mice were also treated with MPTP (9 mg/kg) and 17β-oestradiol. [(3) H]Ro 25-6981 specific binding autoradiography was used to label NMDA receptors containing NR2B subunits. In the frontal and cingulate cortex and striatum, vehicle-treated WT mice had higher [(3) H]Ro 25-6981 specific binding compared to ERKO mice. Cortical [(3) H]Ro 25-6981 specific binding decreased with increasing doses of MPTP in WT and ERKOα but not ERKOβ mice, whereas a dose-related decrease was only observed in the striatum of WT mice remaining low in ERKOα and ERKOβ mice. No effect of 17β-oestradiol treatment in intact or MPTP-lesioned mice of all three genotypes was observed in the cortex, whereas it increased striatal specific binding of intact ERKOβ and MPTP-lesioned WT mice. Striatal [(3) H]Ro 25-6981 specific binding positively correlated with striatal DA concentrations only in WT mice. MPTP and 17β-oestradiol treatments had more limited effects in the hippocampus. Only in the CA3 and dentate gyrus did vehicle and 17β-oestradiol-treated ERKOα mice have higher [(3) H]Ro 25-6981 specific binding than WT and ERKOβ mice, whereas MPTP decreased this specific binding only in the CA1, CA2 and CA3 of ERKOα mice. Hence, brain NMDA receptors were affected by the deletion of ERs, which affect the response to MPTP and 17β-oestradiol treatments with brain region specificity.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".