Sigma-1 Receptor (σ – 1R) Activation and Modulation of NMDA Receptor Surface Expression

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dc.contributor.authorHristova, Elitza
dc.date.accessioned2014-11-07T20:07:14Z
dc.date.available2014-11-07T20:07:14Z
dc.date.created2014
dc.date.issued2014
dc.identifier.urihttp://hdl.handle.net/10393/31784
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-6671
dc.description.abstractThe sigma-1 receptors (σ-1Rs) are endoplasmic reticulum (ER) resident proteins shown to have chaperone-like functions, and are widely distributed throughout the central nervous system (CNS). They reside at a specialized membrane called mitochondria- associated ER-membrane (MAM) and can modulate numerous voltage- and ligand-gated ion channels. One of these channels is the N-methyl-D-aspartate receptor (NMDAR), and σ-1R ligands are able to enhance the potentiation of NMDARs, but the mechanism involved remains poorly understood. Using various biochemical techniques, we show that 90 min following an i.p. injection of σ-1R agonists ((+)-SKF 10,047 (SKF), (+)- Pentazocine (PTZ), or PRE-084 (PRE), there is an increase in the expression of GluN2- containing NMDARs in the rat hippocampus. These results suggest that σ-1R activation is able to enhance NMDAR function by modulating protein expression levels both in the cytosol and on the cell surface. This suggests that σ-1Rs could be excellent therapeutic targets for many neurological disorders, and for the development of novel antipsychotics.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectSigma-1 receptors
dc.subjectNMDA receptors
dc.subjectHippocampus
dc.titleSigma-1 Receptor (σ – 1R) Activation and Modulation of NMDA Receptor Surface Expression
dc.typeThesis
dc.faculty.departmentMédecine cellulaire et moléculaire / Cellular and Molecular Medicine
dc.contributor.supervisorBergeron, Richard
dc.degree.nameMSc
dc.degree.levelmasters
dc.degree.disciplineMédecine / Medicine
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentMédecine cellulaire et moléculaire / Cellular and Molecular Medicine
CollectionThèses, 2011 - // Theses, 2011 -

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