Effect of an AMPA-receptor antagonist, talampanel, on the calcium level of the spinal motor neurons of G93A SOD1 mutant mice

Abstract

Event Abstract Back to Event Effect of an AMPA-receptor antagonist, talampanel, on the calcium level of the spinal motor neurons of G93A SOD1 mutant mice Melinda Paizs1, Massimo Tortarolo2, Caterina Bendotti2 and László Siklós1* 1 Biological Research Center, Institute of Biophysics, Hungary 2 Mario Negri Pharmacological Institute, Laboratory of Molecular Neurobiology, Italy Increased intracellular calcium which might be the consequence of an excess influx through Ca-permeable AMPA receptors has been implicated in the pathomechanism of amyotrophic lateral sclerosis (ALS). To check the protective effect of blocking Ca-influx through these channels, a non-competitive AMPA-receptor antagonist (Talampanel; TA) has been applied to transgenic mice modeling ALS (G93A SOD1 mutants) in a paradigm mimicking the plausible application of the medication in humans: the administration (5mg/kg in 0.1 ml Tween 80 per os daily) has been started when the symptoms had been clearly manifested (17 weeks of age) and lasted until endstage (for appr. 2 weeks). Four G93A transgenic mice were treated with TA, 4 other animals were treated with vehicle only. As additional controls, non-transgenic mice (C57BL/6 line) were treated either with TA (n=4) or with the vehicle (n=2). Intracellular calcium levels in the spinal motor neurons were estimated electron microscopically using the oxalate-pyroantimonate technique. The amount of the reaction products was expressed as their volume fraction (percentage) relative to the perikaryal volume (mean +- s.d.). TA nominally, but not significantly (p=0.42) reduced the calcium level in G93A mice (4.45 +- 0.57) compared to the vehicle (5.30 +- 2.14). Ca-levels in non-transgenic controls were lower than those in the G93A mice with the corresponding treatment (TA: 2.92 +- 0.80, p= 0.16; Vehicle: 2.82 +- 0.14, p= 0.045) and were not significantly different from each other (p=0.92). Thus, TA medication might be able to reduce Ca-increase associated with the disease, but could be ineffective if the treatment is started too late, when the clinical course is already well advanced. Supported by OTKA T048718, GVOP 3.2.1. 2004-04-0052/3.0, TAMOP 4.2.2/08/1/2008-0002 and TéT IT27/2007. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Disorders of the nervous system Citation: Paizs M, Tortarolo M, Bendotti C and Siklós L (2010). Effect of an AMPA-receptor antagonist, talampanel, on the calcium level of the spinal motor neurons of G93A SOD1 mutant mice. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00059 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: 21 Apr 2010; Published Online: 21 Apr 2010. * Correspondence: László Siklós, Biological Research Center, Institute of Biophysics, Szeged, Hungary, siklos@brc.hu 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 Melinda Paizs Massimo Tortarolo Caterina Bendotti László Siklós Google Melinda Paizs Massimo Tortarolo Caterina Bendotti László Siklós Google Scholar Melinda Paizs Massimo Tortarolo Caterina Bendotti László Siklós PubMed Melinda Paizs Massimo Tortarolo Caterina Bendotti László Siklós 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.