Quantification of metabotropic glutamate 2/3 receptor levels in Parkinson’s disease, L-DOPA-induced dyskinesia and dopaminergic psychosis
Bibliographic record
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a progressive depletion of dopamine and complex alterations of neurotransmitter systems such as glutamate. The motor symptoms of PD are traditionally treated with L-3,4-dihydroxyphenylalanine (L-DOPA), but its chronic use is hindered by the development of dyskinesia. In addition, patients with advanced PD are often afflicted with non-motor symptoms such as psychosis and visual hallucinations (VHs). Our lab has discovered that activation of metabotropic glutamate type 2 and 3 (mGlu2/3) receptors alleviates L-DOPA-induced dyskinesia and psychosis-like behaviours in animal models of PD. Although mGlu2/3 receptor modulation has yielded promising results, mechanistic studies on the role of mGlu2/3 receptors and the potential brain areas involved are limited. Thus, with this Thesis, we sought to gain insight into the mechanisms underlying the anti-dyskinetic and anti-psychotic effects conferred by mGlu2/3 activation by performing autoradiographic binding with [3H]-LY- 341,495 in 6-hydroxydopamine (6-OHDA)-lesioned rats and human post-mortem brain tissues of PD patients. Notably, severely dyskinetic 6-OHDA-lesioned rats exhibited a significant increase in binding in the primary motor cortex ipsilateral to the 6-OHDA lesion when compared to mildly dyskinetic 6-OHDA-lesioned rats (P < 0.05). In human post-mortem brain tissues, PD patients who experienced VHs exhibited a significant increase in binding in the external layers of the orbitofrontal cortex when compared with control subjects (P < 0.01). The results of the autoradiographic binding studies suggest that alterations in mGlu2/3 receptor expression may be part of an endogenous compensatory mechanism to alleviate dyskinesia and VHs in PD. Therefore, this Thesis provides insight into a possible mechanism by which mGlu2/3 activation may be alleviating dyskinesia and VHs in PD, supporting the therapeutic potential of by mGlu2/3 receptor modulation
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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 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".