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BDNF, via truncated TrkB receptor, modulates GlyT1 and GlyT2 in astrocytes

2015Journal article Restricted access
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dc.contributor.authorAroeira, Rita I.
dc.contributor.authorSebastião, Ana M
dc.contributor.authorValente, Cláudia A.
dc.date.accessioned2022-02-07T15:53:00Z
dc.date.available2022-02-07T15:53:00Z
dc.date.issued2015
dc.description© 2015 Wiley Periodicals, Inc.pt_PT
dc.description.abstractGlycine transporters (GlyT), GlyT1 and GlyT2, are responsible for the termination of glycine-mediated synaptic activity through removal of neurotransmitter from synaptic cleft. Brain-derived neurotrophic factor (BDNF) activates its high affinity tropomyosin-related kinase (Trk) receptors, namely TrkB, which includes full length (TrkB-FL) and truncated (TrkB-T) isoforms. In this article we evaluated the influence of BDNF upon the activity of glycine transporters in astrocytes. We report that BDNF decreases GlyT1- and GlyT2- mediated [(3) H]glycine transport in primary cultures of astrocytes from rat cerebral cortex. BDNF decreased Vmax but not Km values of transport, which suggests that BDNF induces transporter internalization. Accordingly, dynasore, an inhibitor of dynamin/clathrin-dependent endocytosis, prevented the influence of BDNF upon GlyT-mediated transport. While quantifying mRNA and protein levels, we detected a predominance of truncated isoforms over the TrkB-FL receptor. The effect of BDNF was not abolished by specific inhibitors of PLCγ, PI3K and MAPK, indicating that it did not occur through TrkB-FL canonical pathways. However, BDNF action was lost in the presence of a Rho family-specific blocker (toxin B), a signaling pathway that has been associated to TrkB-T1. Furthermore, the effect of BDNF was abolished upon TrkB-T knockdown in astrocytes by RNA interference. Immunofluorescence assays confirmed an increased GlyT expression in endosomes upon BDNF incubation, which was prevented in the presence of either dynasore or toxin B. We conclude that BDNF, acting on TrkB-T1 receptors, inhibits glycine uptake in astrocytes by promoting GlyT internalization through a Rho-GTPase activity dependent mechanism.pt_PT
dc.description.sponsorshipFundação para a Ciência e a Tecnologia (FCT), Portugal. Grant Number: SFRH/BD/62831/2009pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGlia. 2015 Dec;63(12):2181-2197pt_PT
dc.identifier.doi10.1002/glia.22884pt_PT
dc.identifier.eissn1098-1136
dc.identifier.issn0894-1491
dc.identifier.urihttp://hdl.handle.net/10451/51154
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relationGLYCINERGIC NEUROTRANSMISSION IN RAT HIPPOCAMPUS: A ROLE IN EPILEPTIC STATUS
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/10981136pt_PT
dc.subjectRNA interferencept_PT
dc.subjectBrainpt_PT
dc.subjectGlial cellspt_PT
dc.subjectGlycine transporter 1pt_PT
dc.subjectGlycine transporter 2pt_PT
dc.subjectNeurotrophinspt_PT
dc.titleBDNF, via truncated TrkB receptor, modulates GlyT1 and GlyT2 in astrocytespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleGLYCINERGIC NEUROTRANSMISSION IN RAT HIPPOCAMPUS: A ROLE IN EPILEPTIC STATUS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F62831%2F2009/PT
oaire.citation.endPage2197pt_PT
oaire.citation.issue12pt_PT
oaire.citation.startPage2181pt_PT
oaire.citation.titleGliapt_PT
oaire.citation.volume63pt_PT
person.familyNamePedro Aroeira
person.familyNameSebastião
person.familyNameValente
person.givenNameRita Isabel
person.givenNameAna M
person.givenNameCláudia
person.identifier.ciencia-id7E19-66A0-0A60
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.ciencia-idBD1B-6720-D51D
person.identifier.orcid0000-0002-6886-3334
person.identifier.orcid0000-0001-9030-6115
person.identifier.orcid0000-0001-5405-3130
person.identifier.ridA-3868-2013
person.identifier.scopus-author-id7004409879
person.identifier.scopus-author-id9842734300
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationd0c8104f-ee4f-44eb-af6a-61fff988c6dd
relation.isAuthorOfPublication304abd7f-071b-4447-a8a3-4aa5f0547141
relation.isAuthorOfPublicationf8ed7487-bd16-460b-9e4f-ef0ca623b5ba
relation.isAuthorOfPublication.latestForDiscovery304abd7f-071b-4447-a8a3-4aa5f0547141
relation.isProjectOfPublication441f1551-ec32-4835-b9f0-6a5532c6a652
relation.isProjectOfPublication.latestForDiscovery441f1551-ec32-4835-b9f0-6a5532c6a652

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