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https://hdl.handle.net/10316/106114
Título: | ATP Signaling Controlling Dyskinesia Through P2X7 Receptors | Autor: | Fonteles, Analu A. Neves, Julliana C. S. Menezes, Ana Paula F. Pereira, Juliana F. Silva, Ana Thais A. Cunha, Rodrigo A. Andrade, Geanne M. |
Palavras-chave: | Parkinson’s disease; dyskinesia; P2X7 receptor; neuroinflammation; dopamine D1 receptor; striatum; microglia; astrocyte | Data: | 2020 | Editora: | Frontiers Media S.A. | Projeto: | National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq) CAPES-FCT La Caixa Foundation (LCF/PR/HP17/52190001) CENTRO-01-0145- FEDER-000008:BrainHealth 2020 CENTRO-01-0246- FEDER-000010 FCT; POCI-01-0145-FEDER-03127 |
Título da revista, periódico, livro ou evento: | Frontiers in Molecular Neuroscience | Volume: | 13 | Resumo: | Dopamine replacement therapy with L-3,4-dihydroxyphenylalanine (L-DOPA) is the only temporary therapy for Parkinson's disease (PD), but it triggers dyskinesia over time. Since dyskinesia is associated with increased neuronal firing that bolsters purinergic signaling, we now tested whether the selective and blood-brain barrier-permeable P2X7 receptor antagonist Brilliant Blue-G (BBG, 22.5-45 mg/kg ip) attenuated behavioral, neurochemical and biochemical alterations in rats turned hemiparkinsonian upon unilateral striatal injection of 6-hydroxydopamine (6-OHDA) and treated daily with L-DOPA (30 mg/kg by gavage) for 22 days. The blockade of P2X7 receptors decreased L-DOPA-induced dyskinesia and motor incoordination in hemiparkinsonian rats. In parallel, BBG treatment rebalanced the altered dopamine D1 and D2 receptor density and signaling as well as some neuroinflammation-associated parameters in the striatum and substantia nigra. These findings herald a hitherto unrecognized role for purinergic signaling in the etiopathology of dyskinesia and prompt P2X7 receptor antagonists as novel candidate anti-dyskinesia drugs. | URI: | https://hdl.handle.net/10316/106114 | ISSN: | 1662-5099 | DOI: | 10.3389/fnmol.2020.00111 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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ATP Signaling Controlling Dyskinesia Through P2X7 Receptors.pdf | 3.56 MB | Adobe PDF | Ver/Abrir |
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