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

Autor(es)

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]

Afiliação do(s) autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN CELLULAR NEUROSCIENCE; v. 13, NOV 8 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 12/50880-4 - Células-tronco: dos papéis de receptores de cininas e purinas às aplicações terapêuticas
• Beneficiário: Alexander Henning Ulrich
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/07366-4 - Receptores de purinas e cininas como alvos de estudo e intervenção terapêutica em doenças neurológicas
• Beneficiário: Alexander Henning Ulrich
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/24400-9 - Efeito antiinflamatório do antagonista do receptor P2X7, Brilliant Blue G, e seu impacto na terapia celular em um modelo animal de Doença de Parkinson
• Beneficiário: Carolina de Moura Albino
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica