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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00476

P2Y6 and P2X7 receptor antagonism exerts neuroprotective/ neuroregenerative effects in an animal model of Parkinson’s disease

  • 1University of São Paulo, Brazil

Parkinson’s disease is a neurodegenerative disorder characterized by decreased dopamine bioavailability in the substantia nigra and the striatum. Taking into account that ATP and its metabolites are intensely released in the 6-hydroxydopamine (6-OHDA) animal model of Parkinson’s disease, screening of purinergic receptor gene expression was performed. Effects of pharmacological P2Y6 or P2X7 receptor antagonism were studied in preventing or reversing hemiparkinsonian behavior and dopaminergic deficits in this animal model. P2X7 receptor antagonism with Brilliant Blue G at a dose of 75 mg/kg reestablished dopaminergic nigrostriatal pathway rats injured with 6-OHDA. Selective P2Y6 receptor antagonism by MRS2578 prevented dopaminergic neuron death in SH-SY5Y cells in vitro and in vivo in the substantia nigra of rats injured with 6-OHDA. Moreover, in vivo analysis showed that both treatments were accompanied by a reduction of microglial activation in the substantia nigra. Altogether, these data provide evidence that antagonism of P2X7 and P2Y6 receptors results in neuroregenerative and neuroprotective effects, respectively, possibly through modulation of neuroinflammatory responses.

Keywords: purinergic receptors, brilliant blue G (BBG), P2X7 receptor, P2Y6 receptor, Parkinson’s disease, MRS2578, Microglia

Received: 02 Mar 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Oliveira-Giacomelli, Albino, De Souza, Corrêa-Velloso, Santos, Baranova and Ulrich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Henning Ulrich, University of São Paulo, São Paulo, 05508-010, São Paulo, Brazil,