Metabotropic Glutamate Receptor 5 Negative Allosteric Modulation Effects on Microglia Phenotype

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Curtis, Natasha Ari Suey Lin




Microglia are the resident immunocompetent cells of the central nervous system (CNS). They are extremely plastic and are 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 glutamatergic signaling upon microglial phenotype.






Carleton University

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