Event Abstract

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

  • 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

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Received: 27 Feb 2019; Published Online: 26 Apr 2019.

* Correspondence: Dr. Sara Xapelli, Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal, sxapelli@medicina.ulisboa.pt

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