P2Y6 and P2X7 Receptor Antagonism Exerts Neuroprotective/ Neuroregenerative Effects in an Animal Model of Parkinson’s Disease
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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.
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In animal models for neurodegeneration, P2X7 receptor antagonism exerted beneficial anti-inflammatory effects, indicating that P2X7 receptor activation and subsequent neuroinflammation is tightly related to neurodegeneration worsening.
“In animal models for neurodegeneration P2X7 receptor antagonism exerted beneficial anti-inflammatory effects [138, 139], indicating that P2X7 receptor activation and subsequent neuroinflammation is tightly related to neurodegeneration worsening.”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [139]
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References 60 · Cited by 60
Research works printed but not linked: 1
- Paxinos G. Watson C. (2013). The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition. San Diego, CA: Academic Press.
- Authors
- Oliveira-Giacomelli, Á., M. Albino, C., de Souza, H. D. N., Corrêa-Velloso, J., de Jesus Santos, A. P., Baranova, J., & Ulrich, H.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Ulrich, Henning
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2019-11-08
- Volume
- 13
- Pages
- 476-476
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC6856016
- OpenAlex
- W2981417829
- Cited by
- 60
- References
- 60
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 12 · 2023: 9 · 2022: 10 · 2021: 10 · 2020: 6
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (306392/2017-8, 154512/2018-4, 142137/2019-7)
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2012/50880-4, 2018/07366-4, 2017/24400-9)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (33002010017PO)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Parkinson's disease, P2Y6 receptor, P2X7 receptor, 6-hydroxydopamine, dopaminergic neuron death, substantia nigra, nigrostriatal pathway, neuroprotection, nerve regeneration, microglial activation, neuroinflammation, ATP release, Brilliant Blue G, MRS2578, SH-SY5Y cells
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