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dc.contributor.CRUESPUNIVERSIDADE DE ESTADUAL DE CAMPINASpt_BR
dc.typeArtigo de periódicopt_BR
dc.titlePhosphodiesterase-5 Inhibition Promotes Remyelination By Mcp-1/ccr-2 And Mmp-9 Regulation In A Cuprizone-induced Demyelination Modelpt_BR
dc.contributor.authorde Santana Nunespt_BR
dc.contributor.authorAna Karolina; Raposopt_BR
dc.contributor.authorCatarina; de Oliveirapt_BR
dc.contributor.authorWilma Helena; Thomept_BR
dc.contributor.authorRodolfo; Verinaudpt_BR
dc.contributor.authorLiana; Tovar-Mollpt_BR
dc.contributor.authorFernanda; Peixotopt_BR
dc.contributor.authorChristina Alvespt_BR
unicamp.author.emailnunes.aks@gmail.compt_BR
unicamp.author[Raposo, Catarina] State Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP, Brazilpt_BR
unicamp.authorVerinaud, Liana] Univ Campinas UNICAMP, Dept Struct & Funct Biol, Campinas, SP, Brazilpt_BR
unicamp.author.external[de Santana Nunes, Ana Karolinapt
unicamp.author.externalde Oliveira, Wilma Helenapt
unicamp.author.externalPeixoto, Christina Alves] Aggeu Magalhaes Res Ctr CPqAM, Lab Ultrastruct, BR-50670420 Recife, PE, Brazilpt
unicamp.author.external[de Santana Nunes, Ana Karolinapt
unicamp.author.externalde Oliveira, Wilma Helena] Univ Fed Pernambuco, Recife, PE, Brazilpt
unicamp.author.external[Thome, Rodolfopt
unicamp.author.external[Tovar-Moll, Fernanda] Univ Fed Rio de Janeiro, DOr Inst Res & Educ IDOR, Rio De Janeiro, RJ, Brazilpt
unicamp.author.external[Tovar-Moll, Fernanda] Univ Fed Rio de Janeiro, Inst Biomed Sci ICB, Rio De Janeiro, RJ, Brazilpt
unicamp.author.external[Tovar-Moll, Fernanda] Univ Fed Rio de Janeiro, Natl Ctr Struct Biol & Bioimaging CENABIO, Rio De Janeiro, RJ, Brazilpt
dc.subjectMultiple-sclerosispt_BR
dc.subjectCns Remyelinationpt_BR
dc.subjectProtein-kinasept_BR
dc.subjectOligodendrocytespt_BR
dc.subjectDifferentiationpt_BR
dc.subjectNeuroprotectionpt_BR
dc.subjectExpressionpt_BR
dc.subjectStrokept_BR
dc.subjectBrainpt_BR
dc.subjectCellspt_BR
dc.description.abstractWhile it has recently been shown that sildenafil (Viagra (R)) has a protective effect on myelination/remyelination, the mechanism of this protection is still unknown. In general, cytokines, chemokines and metalloproteinases have a pro-inflammatory action, but can also exert a role in modulating glial cell activation, contributing to the balance of cell response. Investigating these molecules can contribute to clarifying the mechanisms of sildenafil neuroprotection. In addition, it is not known. whether sildenafil is able to restore an already installed neurodegenerative process or if the treatment period is critical for its action. The aim of the present study was to evaluate, in a cuprizone (CPZ)-induced demyelination model, the effects and mechanisms of time-dependent treatment with sildenafil (beginning 15 days after neurodegeneration and continuing for 15 days, or starting concomitantly with neurodegeneration and continuing for 30 days) on neuroinflammation and remyelination. Neuroinflammation and demyelination induced by CPZ in rodents has been widely used as a model of multiple sclerosis (MS). In the present study, five male G7BL/6 mice aged 7-10 weeks were used per group. For four weeks, the groups received either cuprizone (CPZ) 0.2% mixed in feed or CPZ combined with the administration of sildenafil (Viagra, Pfizer, 25 mg/kg) orally in drinking water, starting concurrently with (sild-T0) or 15 days (sild-T15) after the start of CPZ treatment. Control animals received pure food and water. The cerebella were dissected and processed for immunohistochemistry, immunofluorescence (frozen), Western blotting, Luxol fast blue staining and transmission electron microscopy. Magnetic resonance was performed for live animals, after the same treatment, using CPZ 0.3%. CPZ induced an increase in the expression of IL-1 beta and a decrease in MCP-1, CCR-2, MBP and GST-pi, as well as promoting damage in the structure and ultra-structure of the myelin sheath. Interestingly, the administering of sild-TO promoted a further increase of MMP-9, MCP-1, and CCR-2, possibly contributing to changes in the microglia phenotype, which becomes more phagocytic, cleaning myelin debris. It was also observed that, after sild-TO treatment the expression of GST-pi and MBP increased and the myelin structure was improved. However, sild-T15 was not efficient in all aspects, probably due to the short treatment period and to starting after the installation of the degenerative process. Therefore, the present study shows that sildenafil modulates inflammation, with the involvement of MMP-9, MCP-1, and CCR-2, and also contributes to myelin repair. These protective effects were dependent on the therapeutic strategy used. This clarification can strengthen research proposals into the mechanism of action of sildenafil and contribute to the control of neurodegenerative diseases such as MS. (C) 2015 Elsevier Inc. All rights reserved.en
dc.relation.ispartofEXPERIMENTAL NEUROLOGYpt_BR
dc.publisher.countrySAN DIEGOpt_BR
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCEpt_BR
dc.date.issued2016-JANpt_BR
dc.identifier.citationPhosphodiesterase-5 Inhibition Promotes Remyelination By Mcp-1/ccr-2 And Mmp-9 Regulation In A Cuprizone-induced Demyelination Model. Academic Press Inc Elsevier Science, v. 275, p. 143-153 JAN-2016.pt_BR
dc.language.isoenpt_BR
dc.description.volume275pt_BR
dc.description.firstpage143pt_BR
dc.description.lastpage153pt_BR
dc.rightsembargopt_BR
dc.sourceWOSpt_BR
dc.identifier.issn0014-4886pt_BR
dc.identifier.wosidWOS:000367420500016pt_BR
dc.identifier.doi10.1016/j.expneurol.2015.10.013pt_BR
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0014488615301138pt_BR
dc.description.sponsorshipBrazilian fostering agency FACEPEpt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorshipBrazilian fostering agency INBEB [57.3767/2008-4]pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorshipFACEPE [AMD-0094-2.00/1]pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorship1Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorship1Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorship1Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorship1Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsordocumentnumberFAPESP [2011/08005-6]pt
dc.date.available2016-06-07T13:14:37Z-
dc.date.accessioned2016-06-07T13:14:37Z-
dc.description.provenanceMade available in DSpace on 2016-06-07T13:14:37Z (GMT). No. of bitstreams: 1 wos_000367420500016.pdf: 2551493 bytes, checksum: cb1e23963cc7a8394e623d981eee46e0 (MD5) Previous issue date: 2016en
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