Metabotropic Glutamate Receptor 5 Negative Allosteric Modulation Effects on Microglia Phenotype
Bibliographic record
Abstract
Microglia are the resident immunocompetent cells of the central nervous system (CNS).They are extremely plastic and critical for neurogenesis, circuit structure and function, and play a crucial role in early synapse formation.It is thought that metabotropic glutamate receptor 5 (mGluR5) plays a role in the modulation of microglial phenotype.In this thesis, we assessed the impact of the mGluR5 acting negative allosteric drug, (2-chloro-4-[2[2,5-dimethyl-1-[4-(trifluoromethoxy) phenyl] imidazol-4-yl] ethynyl] pyridine (CTEP), alone and the context of the inflammatory endotoxin, lipopolysaccharide (LPS) upon BV2 cells.This was done to assess if mGluR5 plays a role in microglia phenotype modulation.It was found that LPS has an effect on the expression of mGluR5, but otherwise did not have a significant impact upon other markers.This thesis is a starting point for future studies that seek to determine the role of mGluR5 signalling on microglial phenotype.As a disclaimer, the principal investigator notes that this thesis is a work in progress and all data described herein, should be considered preliminary and not final.In part, the thesis was adversely impacted by infrastructure building issues at Carleton University that restricted proper access for the student.include a special thank you to Teresa Fortin whose advice and support allowed for such a prompt completion of this thesis.Also, my gratitude goes to my committee members for their valuable feedback and advice.Finally, I would like to express a special thank you to my supervisor Dr Shawn Hayley.Due to issues arising as a result of the COVID-19 pandemic and problems with access to the recently created Health Sciences Building at Carleton this has been a very valuable learning experience for me.I have learnt so much resilience and steadfastness.I would like to thank everyone who helped me stay committed to the continuing of my education through this difficult time.
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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 | 0.000 | 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) | 0.006 | 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".