Role of NMDA Receptors Subunits NR2A and NR2B on Neuronal Dysfunction caused by Oligomeric Amyloid-beta Peptide

Abstract

Event Abstract Back to Event Role of NMDA Receptors Subunits NR2A and NR2B on Neuronal Dysfunction caused by Oligomeric Amyloid-beta Peptide I. L. Ferreira1, S. I. Mota1, L. M. Bajouco1, C. Pereira1, 2, C. R. Oliveira1, 2 and Ana Cristina-Rego1, 2* 1 University of Coimbra, Center for Neuroscience and Cell Biology, Portugal 2 University of Coimbra, Institute of Biochemistry, Faculty of Medicine, Portugal Alzheimer’s disease (AD) is the leading cause of dementia and the most prevalent neurodegenerative disease in aging. There is growing consensus that neurodegeneration in AD brains is partially due to the overactivation on N-methyl-D-aspartate receptors (NMDARs) leading to excitotoxicity. Indeed, NMDARs activation is implicated in synaptic dysfunction preceding late neurodegeneration in AD pathogenesis, but little is known about the contribution of NR2A/B subunits of NMDARs on amyloid-beta peptide (Abeta)-induced neuronal dysfunction. In this work, we evaluated the contribution of the NMDARs subunits NR2A and NR2B on neuronal dysfunction and cell death induced by oligomeric Abeta, and the role of the peptide on expression and trafficking of NR2A and NR2B. Post-synaptic cultures (17-21 DIV) of rat hippocampal neurons were characterized with the neuronal markers MAP-2, Neu-N and synaptophysin. NR2A/B protein levels increased with age in culture (up to 21 DIV). Exposure of hippocampal neurons to Abeta (0.5 μM for 6h plus 18h- recovery) was not neurotoxic. However, exposure to NMDA (100 μM)/glycine (10 μM) for 15 min largely decreased delayed cell viability, and MK-801 (a non-competitive NMDAR antagonist ) counteracted the neurotoxicity induced by Abeta followed by NMDA treatment. We also investigated the effect of Abeta on total and membrane surface levels of NR2A/B subunits. Abeta exposure selectively increased NR2A, but not NR2B, de novo protein synthesis. Our data also evidenced increased membrane surface levels of NR2B subunits only, upon exposure to Abeta. In addition, single-cell analysis of intracellular Ca2+ changes by confocal microscopy revealed that pre-incubation with Abeta affected the membrane polarization of the cells, and this effect could be prevented by MK-801, suggesting the involvement of NMDARs in the response to Abeta. Altogether, our results suggest the involvement of the NMDARs subunits, NR2A and NR2B, on neuronal dysfunction induced by Abeta.This work is supported by “Fundação para a Ciência e a Tecnologia”, PTDC/SAU-NEU/71675/2006, SFRH/BD/43430/2008, SFRH/BPD/48064/2008. Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Topic: Neurodegenerative Disorders Citation: Ferreira IL, Mota SI, Bajouco LM, Pereira C, Oliveira CR and Cristina-Rego A (2009). Role of NMDA Receptors Subunits NR2A and NR2B on Neuronal Dysfunction caused by Oligomeric Amyloid-beta Peptide. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.109 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Aug 2009; Published Online: 10 Aug 2009. * Correspondence: Ana Cristina-Rego, University of Coimbra, Center for Neuroscience and Cell Biology, Coimbatore, Portugal, a.cristina.rego@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers I. L Ferreira S. I Mota L. M Bajouco C. Pereira C. R Oliveira Ana Cristina-Rego Google I. L Ferreira S. I Mota L. M Bajouco C. Pereira C. R Oliveira Ana Cristina-Rego Google Scholar I. L Ferreira S. I Mota L. M Bajouco C. Pereira C. R Oliveira Ana Cristina-Rego PubMed I. L Ferreira S. I Mota L. M Bajouco C. Pereira C. R Oliveira Ana Cristina-Rego Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.