title: Effects of Low Amyloid-β (Aβ) Concentration on Aβ1-42 Oligomers Binding and GluN2B Membrane Expression.
abstract: Numerous studies have shown that amyloid-β (Aβ) modulate intracellular metabolic cascades and an intracellular Ca2+ homeostasis and a cell surface NMDA receptor expression alteration in Alzheimer's disease (AD). However most of these findings have been obtained by using non-physiological Aβ concentrations. The present study deals with the effect of low Aβ concentrations on cellular homeostasis. We used nerve growth factor-differentiated PC12 cells and murine cortical neurons sequentially treated with low chronic monomeric or small oligomeric Aβ concentrations and high acute oligomeric Aβ concentrations to bring out a priming effect of chronic treatment on subsequently high Aβ concentrations-elicited cellular response. Both cell types indeed displayed an enhanced capacity to bind oligomeric Aβ after monomeric or small oligomeric Aβ application. Furthermore, the results show that monomeric Aβ1-42 application to the cells induces an increase of the Ca2+-response and of the membrane expression of the extrasynaptic subunit of the NMDA receptor GluN2B in PC12 cells, while the opposite effects were observed in cultured neurons. This suggests a sequential interaction of Aβ with the cellular plasma membrane involving monomers or small Aβ oligomers which would facilitate the binding of the deleterious high molecular Aβ oligomers. This mechanism would explain the slow progression of AD in the human nervous system and the deep gradient of neuronal death observed around the amyloid plaques in the nervous tissue.
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives-CNRS, Strasbourg, France.|Universitéde Strasbourg, Strasbourg, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Gilson
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives-CNRS, Strasbourg, France.|Innovative Health Diagnostics SAS, Strasbourg, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Mbebi-Liegeois
authors.affiliation: Universitéde Strasbourg, Strasbourg, France.|CMRR Alsace, Centre Hospitalier de Colmar, France.
authors.forename: François
authors.initials: F
authors.lastname: Sellal
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives-CNRS, Strasbourg, France.|Universitéde Strasbourg, Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: de Barry
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D026481:Blotting, Far-Western; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D002772:Cholera Toxin; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000378:metabolism; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D016229:Amyloid beta-Peptides; C121001:NR2B NMDA receptor; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D018800:Thy-1 Antigens; C075222:amyloid beta-protein (1-42); D002772:Cholera Toxin; D002118:Calcium
keywords: Alzheimer’s disease; NMDA receptor; PC12 cells; amyloid-β; cortical neurons; homeostasis; in vitro model; intracellular calcium; oligomers; pathogenesis