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Stimulation of neural stem cell proliferation by inhibition of phosphodiesterase 5

2014Journal article Open access
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dc.contributor.authorSantos, Ana Isabel
dc.contributor.authorCarreira, Bruno P.
dc.contributor.authorNobre, Rui Jorge
dc.contributor.authorCarvalho, Caetana M.
dc.contributor.authorAraújo, Inês
dc.date.accessioned2018-12-07T14:58:29Z
dc.date.available2018-12-07T14:58:29Z
dc.date.issued2014
dc.description.abstractThe involvement of nitric oxide (NO) and cyclic GMP (cGMP) in neurogenesis has been progressively unmasked over the last decade. Phosphodiesterase 5 (PDE5) specifically degrades cGMP and is highly abundant in the mammalian brain. Inhibition of cGMP hydrolysis by blocking PDE5 is a possible strategy to enhance the first step of neurogenesis, proliferation of neural stem cells (NSC). In this work, we have studied the effect on cell proliferation of 3 inhibitors with different selectivity and potency for PDE5, T0156, sildenafil, and zaprinast, using subventricular zone-(SVZ-) derived NSC cultures. We observed that a short-(6 h) or a long-term (24 h) treatment with PDE5 inhibitors increased SVZ-derived NSC proliferation. Cell proliferation induced by PDE5 inhibitors was dependent on the activation of the mitogen-activated protein kinase (MAPK) and was abolished by inhibitors of MAPK signaling, soluble guanylyl cyclase, and protein kinase G. Moreover, sildenafil neither activated ERK1/2 nor altered p27(Kip1) levels, suggesting the involvement of pathways different from those activated by T0156 or zaprinast. In agreement with the present results, PDE5 inhibitors may be an interesting therapeutic approach for enhancing the proliferation stage of adult neurogenesis.
dc.description.sponsorshipFEDER funds via Programa Operacional Factores de Competitividade (COMPETE); Foundation for Science and Technology (FCT, Portugal) [PTDC/SAU-NEU/102612/2008, PTDC/SAU-OSD/0473/2012, PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014]; FCT [SFRH/BD/77903/2011, SFRH/BPD/78901/2011, SFRH/BPD/66705/2009]
dc.identifier.doi10.1155/2014/878397
dc.identifier.issn1687-966X
dc.identifier.issn1687-9678
dc.identifier.urihttp://hdl.handle.net/10400.1/12045
dc.language.isoeng
dc.peerreviewedyes
dc.publisherHindawi Publishing Corporation
dc.subjectCyclic nucleotide phosphodiesterase
dc.subjectNitric oxide synthase
dc.subjectCamp specific phosphodiesterase
dc.subjectFocal cerebral ischemia
dc.subjectProtein kinase G
dc.subjectSubventricular zone
dc.subjectFunctional recovery
dc.subjectDentate gyrus
dc.subjectAdult neurogenesis
dc.subjectOlfactory bulb
dc.titleStimulation of neural stem cell proliferation by inhibition of phosphodiesterase 5
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage878397
oaire.citation.titleStem Cells International
person.familyNameSantos
person.familyNameCarreira
person.familyNamePombinho de Araújo
person.givenNameAna Isabel
person.givenNameBruno P.
person.givenNameInês Maria
person.identifierF-4703-2012
person.identifier.ciencia-idA31D-E831-28E8
person.identifier.ciencia-id8F1E-5352-8ADF
person.identifier.ciencia-idD11F-D4CA-2947
person.identifier.orcid0000-0003-2070-0285
person.identifier.orcid0000-0002-7874-6545
person.identifier.orcid0000-0002-2438-0111
person.identifier.scopus-author-id55019179900
person.identifier.scopus-author-id19337042300
person.identifier.scopus-author-id56271084100
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication71b27a1a-a03a-4d9b-80e6-60d22840f569
relation.isAuthorOfPublication5e35b22a-421c-4a4b-9081-916240299474
relation.isAuthorOfPublication1d0c21f4-0f4b-4589-8412-fe1079419774
relation.isAuthorOfPublication.latestForDiscovery71b27a1a-a03a-4d9b-80e6-60d22840f569

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