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Unravelling a novel role for cannabidivarin in the modulation of subventricular zone postnatal neurogenesis

2023Artigo científico Acesso aberto
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dc.contributor.authorLourenço, Diogo M.
dc.contributor.authorSoares, Rita
dc.contributor.authorSá Santos, Sónia
dc.contributor.authorMateus, Joana
dc.contributor.authorRodrigues, Rui S.
dc.contributor.authorMoreira, João B.
dc.contributor.authorVaz, Sandra H.
dc.contributor.authorSebastião, Ana M
dc.contributor.authorSolá, Susana
dc.contributor.authorXapelli, Sara
dc.date.accessioned2025-05-29T13:47:32Z
dc.date.available2025-05-29T13:47:32Z
dc.date.issued2023
dc.description© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by- nc/4.0/).pt_PT
dc.description.abstractPostnatal neurogenesis has been shown to rely on the endocannabinoid system. Here we aimed at unravelling the role of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, with high affinity for the non-classical cannabinoid receptor TRPV1, on subventricular zone (SVZ) postnatal neurogenesis. Using the neurosphere assay, SVZ-derived neural stem/progenitor cells (NSPCs) were incubated with CBDV and/or 5'-Iodoresinferotoxin (TRPV1 antagonist), and their role on cell viability, proliferation, and differentiation were dissected. CBDV was able to promote, through a TRPV1-dependent mechanism, cell survival, cell proliferation and neuronal differentiation. Furthermore, pulse-chase experiments revealed that CBDV-induced neuronal differentiation was a result of cell cycle exit of NSPCs. Regarding oligodendrocyte differentiation, CBDV inhibited oligodendrocyte differentiation and maturation. Since our data suggested that the CBDV-induced modulation of NSPCs acted via TRPV1, a sodium-calcium channel, and that intracellular calcium levels are known regulators of NSPCs fate and neuronal maturation, single cell calcium imaging was performed to evaluate the functional response of SVZ-derived cells. We observed that CBDV-responsive cells displayed a two-phase calcium influx profile, being the initial phase dependent on TRPV1 activation. Taken together, this work unveiled a novel and untapped neurogenic potential of CBDV via TRPV1 modulation. These findings pave the way to future neural stem cell biological studies and repair strategies by repurposing this non-psychoactive cannabinoid as a valuable therapeutic target.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia with fellowships PD/BD/141784/2018 and COVID/BD/152658/2022 (DML); PD/BD/128280/2017 (RS); PD/BD/150343/2019 (JM); SFRH/BD/129710/2017 (RR); 2020.04492.BD (JBM). This project has received funding from H2020-WIDESPREAD-05-2020-Twinning (EpiEpinet) under grant agreement No 952455; International Society for Neurochemistry (ISN) Career Development Grant and International Brain Research Organization (IBRO) Early Career Award. We also acknowledge the funding PPBI-POCI-01-0145-FEDER-022122.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEur J Pharmacol. 2023 Nov 15:959:176079pt_PT
dc.identifier.doi10.1016/j.ejphar.2023.176079pt_PT
dc.identifier.eissn1879-0712
dc.identifier.issn0014-2999
dc.identifier.urihttp://hdl.handle.net/10400.5/101125
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationPPBI-POCI-01-0145-FEDER-022122pt_PT
dc.relationPD/BD/141784/2018pt_PT
dc.relationCOVID/BD/152658/2022pt_PT
dc.relationPD/BD/128280/2017pt_PT
dc.relationPD/BD/150343/2019pt_PT
dc.relationSFRH/BD/129710/2017pt_PT
dc.relation2020.04492.BDpt_PT
dc.relation952455pt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/european-journal-of-pharmacologypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectAdult neurogenesispt_PT
dc.subjectCannabidivarinpt_PT
dc.subjectNeural stem cellspt_PT
dc.subjectOligodendrogenesispt_PT
dc.subjectSubventricular zonept_PT
dc.subjectTRPV1pt_PT
dc.titleUnravelling a novel role for cannabidivarin in the modulation of subventricular zone postnatal neurogenesispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleEuropean Journal of Pharmacologypt_PT
oaire.citation.volume959pt_PT
person.familyNameLourenço
person.familyNameSoares
person.familyNameSá Santos
person.familyNameMateus
person.familyNameRodrigues
person.familyNameMoreira
person.familyNameHenriques Vaz
person.familyNameSebastião
person.familyNameZeferino Solá da Cruz
person.familyNameXapelli
person.givenNameDiogo
person.givenNameRita
person.givenNameSónia
person.givenNameJoana
person.givenNameRui S
person.givenNameJoão
person.givenNameSandra Cristina
person.givenNameAna M
person.givenNameSusana
person.givenNameSara
person.identifier694579
person.identifier694430
person.identifierM-5251-2013
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person.identifier.ciencia-id2512-BC8E-4984
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person.identifier.ciencia-id7110-C8C3-ED42
person.identifier.orcid0000-0001-9994-0315
person.identifier.orcid0000-0003-2072-0358
person.identifier.orcid0000-0002-8207-3937
person.identifier.orcid0000-0003-1606-292X
person.identifier.orcid0000-0002-9343-745X
person.identifier.orcid0000-0002-7736-844X
person.identifier.orcid0000-0003-4258-9397
person.identifier.orcid0000-0001-9030-6115
person.identifier.orcid0000-0003-2036-797X
person.identifier.orcid0000-0001-6854-2509
person.identifier.ridK-3959-2013
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person.identifier.scopus-author-id6508212575
person.identifier.scopus-author-id7004409879
person.identifier.scopus-author-id7004195841
person.identifier.scopus-author-id8721560200
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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