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Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

2013-05Journal article Open access
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dc.contributor.authorXapelli, Sara
dc.contributor.authorAgasse, Fabienne
dc.contributor.authorSarda-Arroyo, Laura
dc.contributor.authorBernardino, Liliana
dc.contributor.authorSantos, Tiago
dc.contributor.authorRibeiro, Filipa F.
dc.contributor.authorValero, Jorge
dc.contributor.authorBraganca, José
dc.contributor.authorSchitine, Clarissa
dc.contributor.authorde Melo Reis, Ricardo A.
dc.contributor.authorSebastiao, Ana M.
dc.contributor.authorMalva, Joao O.
dc.date.accessioned2018-12-07T14:57:52Z
dc.date.available2018-12-07T14:57:52Z
dc.date.issued2013-05
dc.description.abstractThe endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.
dc.description.sponsorshipFundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologia
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1371/journal.pone.0063529
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10400.1/11739
dc.language.isoeng
dc.peerreviewedyes
dc.publisherPublic Library of Science
dc.relationHistamine versus antihistamines: new modulators of neurogenesis?
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectNeural progenitor proliferation
dc.subjectCentral-nervous-system
dc.subjectGrowth-factor receptor
dc.subjectEndocannabinoid system
dc.subjectStem-cells
dc.subjectAdult neurogenesis
dc.subjectNeuronal differentiation
dc.subjectP19 Cells
dc.subjectBrain
dc.subjectPathway
dc.titleActivation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleHistamine versus antihistamines: new modulators of neurogenesis?
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-NEU%2F104415%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-NEU%2F101783%2F2008/PT
oaire.citation.issue5
oaire.citation.startPagee63529
oaire.citation.titlePLoS ONE
oaire.citation.volume8
oaire.fundingStream5876-PPCDTI
oaire.fundingStream5876-PPCDTI
person.familyNameBragança
person.givenNameJosé
person.identifier.ciencia-idAC1D-FA9D-F66F
person.identifier.orcid0000-0001-9566-400X
person.identifier.scopus-author-id6602220001
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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relation.isAuthorOfPublication.latestForDiscovery27334e02-e955-4939-b9b5-bdee5b5f9328
relation.isProjectOfPublication7d1a83cf-d7e7-4e43-9c2c-9986c50b6bc5
relation.isProjectOfPublicationde8b9fdf-4b7d-482f-b579-0b949c293625
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