Putative role of adenosine A2A receptors in promoting remyelination through adult oligodendrogenesis in the EAE Model

Abstract

Event Abstract Back to Event Putative role of adenosine A2A receptors in promoting remyelination through adult oligodendrogenesis in the EAE Model Marta A. Gomes1, 2, Joana M. Mateus1, 2, Ana M. Sebastião1, 2 and Sara Xapelli1, 2* 1 Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Portugal 2 Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal Multiple Sclerosis (MS) is a chronic neuroinflammatory autoimmune demyelinating disease of the central nervous system (CNS). MS pathogenesis begins with an exacerbated inflammatory response that deteriorates the myelin sheath, produced by oligodendrocytes (OLGs) in the CNS, which insulates neuronal axons. Myelinating OLGs result from the differentiation of oligodendrocyte progenitor cells (OPCs) present in the brain parenchyma but also from neural stem cells (NSCs) of the subventricular zone (SVZ) neurogenic niche. Previous studies have reported a spontaneous phenomenon of remyelination in MS, through the migration of OLGs to demyelinated areas. Furthermore, adenosine A2A Receptors (A2AR) have been shown to have a protective role against inflammation in Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS, attenuating the phenotype of the disease. However, A2AR role in modulating adult oligodendrogenesis under EAE pathogenesis has never been studied. Thus, this project aimed to assess the role of A2AR in promoting OLGs differentiation and myelination under EAE pathogenesis. Female C57BL/6 mice were immunized with MOG35-55 and injected with Pertussis toxin to induce EAE. EAE mice were administered in the lateral ventricle with vehicle or with A2AR agonist (CGS21680, 100 nM) for 26 days using micro-osmotic pumps. Behavioural tests were performed to evaluate EAE model progression, along with cellular and molecular analyses to assess A2AR agonist influence on inflammation, OLG differentiation and de- and remyelination. Overall, EAE disease incidence was of only 40% which constrained the significance of the results. EAE animals showed impaired performance in behavioral tests as EAE phenotype was progressing, although no differences were observed between the vehicle and the CGS21680 groups. Moreover, no tendencies for changes were observed at the molecular level, regarding either inflammatory and cell differentiation signaling pathways. Regarding demyelination, both luxol fast blue assay and immunohistochemical staining for myelin proteins showed that myelin amounts in both EAE vehicle and CGS21680 animals were similar to control animals. Taken together, EAE induction protocol and CGS21680 dose should be optimized to allow further conclusions on A2AR relevance for regenerative therapies in MS. Keywords: Multiple Sclerosis, EAE (experimental autoimmune encephalomyelitis), Adenosine A2A receptor (A2AR), Adult Oligodendrogenesis, remyelination Conference: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019. Presentation Type: Poster presentation Topic: Glia / Neuroinflammation Citation: Gomes MA, Mateus JM, Sebastião AM and Xapelli S (2019). Putative role of adenosine A2A receptors in promoting remyelination through adult oligodendrogenesis in the EAE Model. Front. Cell. Neurosci. Conference Abstract: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019). doi: 10.3389/conf.fncel.2019.01.00008 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: 27 Feb 2019; Published Online: 27 Sep 2019. * Correspondence: Dr. Sara Xapelli, Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal, sxapelli@medicina.ulisboa.pt 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 Marta A Gomes Joana M Mateus Ana M Sebastião Sara Xapelli Google Marta A Gomes Joana M Mateus Ana M Sebastião Sara Xapelli Google Scholar Marta A Gomes Joana M Mateus Ana M Sebastião Sara Xapelli PubMed Marta A Gomes Joana M Mateus Ana M Sebastião Sara Xapelli 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.