ATP Signaling Controlling Dyskinesia Through P2X7 Receptors

Frontiers in Molecular Neuroscience

Rodrigo A. Cunha²  Juliana F. Pereira³  Geanne M. Andrade³  Julliana C. S. Neves⁴  Analu A. Fonteles⁴  Ana Paula F. Menezes⁴  Ana Thais A. Silva⁴ 

[1] CNC-Center for Neuroscience and Cell Biology, Coimbra, Portugal;Faculty of Medicine, University of Coimbra, Coimbra, Portugal;Post-Graduate Program in Medical Sciences, Department of Medicine, Faculty of Medicine, Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, Brazil;Post-Graduate Program in Pharmacology, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil;

关键词: Parkinson’s disease;    dyskinesia;    P2X7 receptor;    neuroinflammation;    dopamine D1 receptor;    striatum;   

DOI  :  10.3389/fnmol.2020.00111

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown