Role of the purinergic system in controlling blood-brain barrier functions upon ischemic conditions: focus on ATP-metabolizing enzymes

Abstract

Event Abstract Back to Event Role of the purinergic system in controlling blood-brain barrier functions upon ischemic conditions: focus on ATP-metabolizing enzymes Stefania Ceruti1*, Laura Colombo1, Giuila Magni1, Francesca Vigano1, Zsófia Gazdag2, Marta Boccazzi1, Beáta Sperlágh2, Mária Deli3, Maria P. Abbracchio1 and Ágnes Kittel2 1 Università degli Studi di Milano, Department of Pharmacological Sciences, Italy 2 Hungarian Academy of Science, Institute of Experimental Medicine, Hungary 3 Hungarian Academy of Science, Institute of Biophysics, Biological Research Center, Hungary The blood-brain barrier (BBB) is composed of endothelial cells, pericytes and astrocytes, and serves as interface between the blood flow and the central nervous system (CNS). Since BBB deregulation plays important role in the pathogenesis of several CNS diseases spanning from brain tumors to stroke, understanding the molecular mechanisms controlling BBB functions might help unveiling new therapeutic targets to brain pathologies. Extracellular nucleotides are important signaling molecules both in physiological and pathological conditions. Their actions are mediated by 7 ionotropic P2X and 8 metabotropic P2Y purinergic receptors, and terminated by metabolizing enzymes, namely ectonucleotidases (NTPDases) and 5’-nucleotidase. To date the role of purinergic transmission in controlling BBB functions is not fully understood. Therefore, we used a new in vitro cell culture model of BBB to investigate the expression and distribution of NTPDases and P2Y receptors either in control conditions or following exposure to ischemia. RT-PCR analysis showed that astrocytes and pericytes expressed all the cloned P2Y receptors, that endothelial cells showed only the P2Y1,2,4 subtypes, and that NTPDase1 and 2 were expressed by all the three types of cell. Application of oxygen-glucose deprivation (OGD), which mimics cytotoxicity induced by ischemia in vivo, showed that endothelial cells were extremely susceptible to cell death, whereas astrocytes and pericytes were more resistant. A semi-quantitative assay highlighted increased ecto-ATPase activity following exposure to OGD in the three types of cell, both when grown separately and in triple co-culture. Our data show the usefulness of this new in vitro model to demonstrate a role for extracellular nucleotides in modulating BBB responses to ischemic events, and to determine if the purinergic system could represent a new target for the development of effective therapies to brain pathologies. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Disorders of the nervous system Citation: Ceruti S, Colombo L, Magni G, Vigano F, Gazdag Z, Boccazzi M, Sperlágh B, Deli M, Abbracchio MP and Kittel Á (2010). Role of the purinergic system in controlling blood-brain barrier functions upon ischemic conditions: focus on ATP-metabolizing enzymes. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00030 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: 19 Apr 2010; Published Online: 19 Apr 2010. * Correspondence: Stefania Ceruti, Università degli Studi di Milano, Department of Pharmacological Sciences, Milan, Italy, stefania.ceruti@unimi.it 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 Stefania Ceruti Laura Colombo Giuila Magni Francesca Vigano Zsófia Gazdag Marta Boccazzi Beáta Sperlágh Mária Deli Maria P Abbracchio Ágnes Kittel Google Stefania Ceruti Laura Colombo Giuila Magni Francesca Vigano Zsófia Gazdag Marta Boccazzi Beáta Sperlágh Mária Deli Maria P Abbracchio Ágnes Kittel Google Scholar Stefania Ceruti Laura Colombo Giuila Magni Francesca Vigano Zsófia Gazdag Marta Boccazzi Beáta Sperlágh Mária Deli Maria P Abbracchio Ágnes Kittel PubMed Stefania Ceruti Laura Colombo Giuila Magni Francesca Vigano Zsófia Gazdag Marta Boccazzi Beáta Sperlágh Mária Deli Maria P Abbracchio Ágnes Kittel 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.