Brilliant Blue G, But Not Fenofibrate, Treatment Reverts Hemiparkinsonian Behavior and Restores Dopamine Levels in an Animal Model of Parkinson's Disease

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dc.citation.issue4
dc.citation.volume26
dc.contributor.authorFerrazoli, Eneas Galdini [UNIFESP]
dc.contributor.authorde Souza, Hellio D. N.
dc.contributor.authorNascimento, Isis C.
dc.contributor.authorOliveira-Giacomelli, Agatha
dc.contributor.authorSchwindt, Telma T.
dc.contributor.authorBritto, Luiz R.
dc.contributor.authorUlricht, Henning
dc.coveragePutnam Valley
dc.date.accessioned2020-07-31T12:46:42Z
dc.date.available2020-07-31T12:46:42Z
dc.date.issued2017
dc.description.abstractParkinson's disease (PD) is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra and their projections to the striatum. Several processes have been described as potential inducers of the dopaminergic neuron death, such as inflammation, oxidative stress, and mitochondrial dysfunction. However, the death of dopaminergic neurons seems to be multifactorial, and its cause remains unclear. ATP-activating purinergic receptors influence various physiological functions in the CNS, including neurotransmission. Purinergic signaling is also involved in pathological scenarios, where ATP is extensively released and promotes sustained purinergic P2X7 receptor (P2X7R) activation and consequent induction of cell death. This effect occurs, among other factors, by oxidative stress and during the inflammatory response. On the other hand, peroxisome proliferator-activated receptor-gamma coactivator la (PGC-1 alpha) is involved in energy metabolism and mitochondrial biogenesis. Expression and activity upregulation of this protein has been related with reduction of oxidative stress and neuroprotection. Therefore, P2X7R and PGC-1 alpha are potential targets in the treatment of PD. Here hemiparkinsonism was induced by unilateral stereotactic injection of 6-OHDA in a rat model. After 7 days, the establishment of PD was confirmed and followed by treatment with the P2X7R antagonist Brilliant Blue G (BBG) or PGC-1 alpha agonist fenofibrate. BBG, but not fenofibrate, reverted hemiparkinsonian behavior accompanied by an increase in tyrosine hydroxylase immunoreactivity in the substantia nigra. Our results suggest that the P2X7R may be a therapeutic target in Parkinson's disease.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Neurol & Neurocirurgia, Disciplina Neurol Neurociencia, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Quim, Dept Bioquim, Ave Prof Lineu Prestes 748, BR-05508900 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, Sao Paulo, Brazil
dc.description.affiliationUnifespDepartamento de Neurologia e Neurocirurgia, Disciplina de Neurologia/Neurociência, Universidade Federal de São Paulo, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (FAPESP) [2012/50880-4]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil [486294/2012-9, 467465/2014-2]
dc.description.sponsorshipFAPESP [2011/09852-4, 2012/20685-5, 2015/18730-0]
dc.description.sponsorshipCNPq
dc.description.sponsorshipIDFAPESP: 2012/50880-4
dc.description.sponsorshipIDCNPq: 486294/2012-9
dc.description.sponsorshipIDCNPq: 467465/2014-2
dc.description.sponsorshipIDFAPESP: 2011/09852-4
dc.description.sponsorshipIDFAPESP: 2012/20685-5
dc.description.sponsorshipIDFAPESP: 2015/18730-0
dc.format.extent669-677
dc.identifierhttp://dx.doi.org/10.3727/096368917X695227
dc.identifier.citationCell Transplantation. Putnam Valley, v. 26, n. 4, p. 669-677, 2017.
dc.identifier.doi10.3727/096368917X695227
dc.identifier.issn0963-6897
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56316
dc.identifier.wosWOS:000400124700012
dc.language.isoeng
dc.publisherCognizant Communication Corp
dc.relation.ispartofCell Transplantation
dc.relation.ispartof23rd Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair (ASNTR)
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectParkinson's disease (PD)en
dc.subjectP2X7 receptoren
dc.subjectBrilliant Blue G (BBG)en
dc.subjectPGC-1 alphaen
dc.subjectFenofibrateen
dc.titleBrilliant Blue G, But Not Fenofibrate, Treatment Reverts Hemiparkinsonian Behavior and Restores Dopamine Levels in an Animal Model of Parkinson's Diseaseen
dc.typeinfo:eu-repo/semantics/article
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