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Brain-derived neurotrophic factor (BDNF) role in cannabinoid-mediated neurogenesis

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dc.contributor.authorFerreira, Filipa Fiel
dc.contributor.authorRibeiro, Filipa
dc.contributor.authorRodrigues, Rui S.
dc.contributor.authorSebastião, Ana M
dc.contributor.authorXapelli, Sara
dc.date.accessioned2022-12-06T14:29:07Z
dc.date.available2022-12-06T14:29:07Z
dc.date.issued2018
dc.descriptionCopyright © 2018 Ferreira, Ribeiro, Rodrigues, Sebastião and Xapelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.pt_PT
dc.description.abstractThe adult mammalian brain can produce new neurons in a process called adult neurogenesis, which occurs mainly in the subventricular zone (SVZ) and in the hippocampal dentate gyrus (DG). Brain-derived neurotrophic factor (BDNF) signaling and cannabinoid type 1 and 2 receptors (CB1R and CB2R) have been shown to independently modulate neurogenesis, but how they may interact is unknown. We now used SVZ and DG neurosphere cultures from early (P1-3) postnatal rats to study the CB1R and CB2R crosstalk with BDNF in modulating neurogenesis. BDNF promoted an increase in SVZ and DG stemness and cell proliferation, an effect blocked by a CB2R selective antagonist. CB2R selective activation promoted an increase in DG multipotency, which was inhibited by the presence of a BDNF scavenger. CB1R activation induced an increase in SVZ and DG cell proliferation, being both effects dependent on BDNF. Furthermore, SVZ and DG neuronal differentiation was facilitated by CB1R and/or CB2R activation and this effect was blocked by sequestering endogenous BDNF. Conversely, BDNF promoted neuronal differentiation, an effect abrogated in SVZ cells by CB1R or CB2R blockade while in DG cells was inhibited by CB2R blockade. We conclude that endogenous BDNF is crucial for the cannabinoid-mediated effects on SVZ and DG neurogenesis. On the other hand, cannabinoid receptor signaling is also determinant for BDNF actions upon neurogenesis. These findings provide support for an interaction between BDNF and endocannabinoid signaling to control neurogenesis at distinct levels, further contributing to highlight novel mechanisms in the emerging field of brain repair.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia (FCT) Portugal (PTDC/DTP-FTO/3346/2014). RR (SFRH/BD/129710/2017) and FR (SFRH/BD/74662/2010) were in receipt of a fellowship from FCT. AS thanks the H2020 Twinning Action from EU (SynaNet 692340). SX is an iFCT researcher (IF/01227/2015). BDNF was kindly given by Regeneron. Funded by LISBOA-01-0145-FEDER-007391, project co-funded by FEDER, through POR Lisboa 2020 – Programa Operacional Regional de Lisboa, PORTUGAL 2020, and Fundação para a Ciência e a Tecnologia.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Cell Neurosci. 2018 Nov 28;12:441pt_PT
dc.identifier.doi10.3389/fncel.2018.00441pt_PT
dc.identifier.eissn1662-5102
dc.identifier.urihttp://hdl.handle.net/10451/55355
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relationLISBOA-01-0145-FEDER-007391pt_PT
dc.relationSynaptic mechanisms involved in the brain cannabinoid actions and their modulation by adenosine receptors: implications for memory and mood control
dc.relationCB2ExStress: a neurogenic strategy to tackle mood disorders
dc.relationADENOSINE A2A RECEPTOR MODULATION OF NEURONAL MATURATION
dc.relationNeurologic and Psychiatric Disorders: from synapses to networks
dc.relation.publisherversionhttps://www.frontiersin.org/journals/cellular-neurosciencept_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectBrain-derived neurotrophic factor (BDNF)pt_PT
dc.subjectCannabinoid receptorspt_PT
dc.subjectDentate gyruspt_PT
dc.subjectPostnatal neurogenesispt_PT
dc.subjectSubventricular zonept_PT
dc.titleBrain-derived neurotrophic factor (BDNF) role in cannabinoid-mediated neurogenesispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleSynaptic mechanisms involved in the brain cannabinoid actions and their modulation by adenosine receptors: implications for memory and mood control
oaire.awardTitleCB2ExStress: a neurogenic strategy to tackle mood disorders
oaire.awardTitleADENOSINE A2A RECEPTOR MODULATION OF NEURONAL MATURATION
oaire.awardTitleNeurologic and Psychiatric Disorders: from synapses to networks
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FDTP-FTO%2F3346%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F129710%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F74662%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/692340/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F01227%2F2015%2FCP1317%2FCT0001/PT
oaire.citation.titleFrontiers in Cellular Neurosciencept_PT
oaire.citation.volume12pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamH2020
oaire.fundingStreamInvestigador FCT
person.familyNameRibeiro
person.familyNameRodrigues
person.familyNameSebastião
person.familyNameXapelli
person.givenNameFilipa
person.givenNameRui S
person.givenNameAna M
person.givenNameSara
person.identifier129383
person.identifier.ciencia-id6916-485D-36C3
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.ciencia-id7110-C8C3-ED42
person.identifier.orcid0000-0002-4006-7328
person.identifier.orcid0000-0002-9343-745X
person.identifier.orcid0000-0001-9030-6115
person.identifier.orcid0000-0001-6854-2509
person.identifier.ridS-1079-2018
person.identifier.scopus-author-id7004409879
person.identifier.scopus-author-id8721560200
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
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
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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