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TitleNMDA receptors are upregulated and trafficked to the plasma membrane after sigma-1 receptor activation in the rat hippocampus.
Publication TypeJournal Article
Year of Publication2014
AuthorsPabba, Mohan, Adrian Y. C. Wong, Nina Ahlskog, Elitza Hristova, Dante Biscaro, Wissam Nassrallah, Johnny K. Ngsee, Melissa Snyder, Jean-Claude Béïque, and Richard Bergeron
JournalJ Neurosci
Date Published2014 Aug 20
KeywordsAnimals, Cell Membrane, Ethylenediamines, Hippocampus, Intracellular Signaling Peptides and Proteins, Male, Membrane Proteins, Mice, Mice, Knockout, Morpholines, Pentazocine, Phenazocine, Piperazines, Protein Transport, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate, Receptors, sigma, Subcellular Fractions, Time Factors, Up-Regulation

Sigma-1 receptors (σ-1Rs) are endoplasmic reticulum resident chaperone proteins implicated in many physiological and pathological processes in the CNS. A striking feature of σ-1Rs is their ability to interact and modulate a large number of voltage- and ligand-gated ion channels at the plasma membrane. We have reported previously that agonists for σ-1Rs potentiate NMDA receptor (NMDAR) currents, although the mechanism by which this occurs is still unclear. In this study, we show that in vivo administration of the selective σ-1R agonists (+)-SKF 10,047 [2S-(2α,6α,11R*]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-methano-3-benzazocin-8-ol hydrochloride (N-allylnormetazocine) hydrochloride], PRE-084 (2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate hydrochloride), and (+)-pentazocine increases the expression of GluN2A and GluN2B subunits, as well as postsynaptic density protein 95 in the rat hippocampus. We also demonstrate that σ-1R activation leads to an increased interaction between GluN2 subunits and σ-1Rs and mediates trafficking of NMDARs to the cell surface. These results suggest that σ-1R may play an important role in NMDAR-mediated functions, such as learning and memory. It also opens new avenues for additional studies into a multitude of pathological conditions in which NMDARs are involved, including schizophrenia, dementia, and stroke.

Alternate JournalJ. Neurosci.
PubMed ID25143613
Grant ListMOP-115062 / / Canadian Institutes of Health Research / Canada
MOP-79360 / / Canadian Institutes of Health Research / Canada