P2Y6 and P2X7 Receptor Antagonism Exerts Neuroprotective/ Neuroregenerative Effects in an Animal Model of Parkinson's Disease

Author(s)

Oliveira-Giacomelli, Agatha ^[1] ; Albino, Carolina M. ^[1] ; Nobrega de Souza, Hellio Danny ^[1] ; Correa-Velloso, Juliana ^[1] ; de Jesus Santos, Ana Paula ^[1] ; Baranova, Juliana ^[1] ; Ulrich, Henning ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Neurosci Lab, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR NEUROSCIENCE; v. 13, NOV 8 2019.
• Web of Science Citations: 0

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by decreased dopamine bioavailability in the substantia nigra and the striatum. Taking into account that adenosine-5'-triphosphate (ATP) and its metabolites are intensely released in the 6-hydroxydopamine (6-OHDA) animal model of PD, 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 (BBG) at a dose of 75 mg/kg re-established the dopaminergic nigrostriatal pathway in 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 or P2Y6 receptors results in neuroregenerative or neuroprotective effects, respectively, possibly through modulation of neuroinflammatory responses. (AU)

• FAPESP's process: 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/24400-9 - Anti-inflammatory effect of the P2X7 receptor antagonist, brilliant blue g, and its impact on cell therapy in an animal model of Parkinson's Disease
• Grantee: Carolina de Moura Albino
• Support Opportunities: Scholarships in Brazil - Scientific Initiation