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BDNF modulates glycine uptake in hippocampal synaptosomes by decreasing membrane insertion of glycine transporter 2

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dc.contributor.authorAroeira, Rita I.
dc.contributor.authorVaz, Sandra H.
dc.contributor.authorSebastião, Ana M
dc.contributor.authorValente, Cláudia A.
dc.date.accessioned2022-02-24T16:26:05Z
dc.date.available2022-02-24T16:26:05Z
dc.date.issued2016
dc.description© 2016 Elsevier Ltd. All rights reserved.pt_PT
dc.description.abstractGlycine transporter 2 (GlyT2) is localized in the nerve terminals of glycinergic neurons, promoting glycine uptake and ensuring the refilling of glycinergic vesicles. Brain-derived neurotrophic factor (BDNF) activates its high affinity TrkB receptors, which occur in two isoforms, full length (TrkB-FL) and truncated (TrkB-T1/T2). After BDNF binding to TrkB receptor, several intracellular cascades are triggered, specifically PLC, Akt and MAPK signalling pathways. We herein show that BDNF decreases [(3)H]glycine uptake mediated by GlyT2 in isolated nerve endings (synaptosomes) obtained from rat hippocampus, by reducing the maximum velocity (Vmax) of transport while not influencing the transporter affinity constant (Km) for glycine. Western Blot analysis detected both TrkB receptor isoforms in the synaptosomes but the BDNF effect seems to be mediated by TrkB-FL since: 1) the tyrosine kinase inhibitor, k252a, prevented the effect of BDNF, and 2) the effect of BDNF was lost in the presence of specific inhibitors of TrkB signalling pathways, namely U73122, LY294002 and U0126 (inhibitors of PLC, Akt and MAPK pathways, respectively). Monensin, a transporter recycling inhibitor, prevented the BDNF action upon glycine uptake, suggesting that BDNF reduces GlyT2 insertion in the plasma membrane. It is concluded that BDNF effect upon glycine uptake into glycinergic nerve terminals requires the activation of the TrkB-FL receptor and its canonical signalling pathways and occurs by inhibiting GlyT2 membrane incorporation.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal. Rita I. Aroeira and Sandra H. Vaz were in receipt of fellowships from FCT, SFRH/BD/62831/2009 and SFRH/BPD/81627/2011, respectively. BDNF was a kind gift from Regeneron Pharmaceuticals.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNeurochemistry International 99 (2016) 94e102 95pt_PT
dc.identifier.doi10.1016/j.neuint.2016.06.007pt_PT
dc.identifier.eissn1872-9754
dc.identifier.issn0197-0186
dc.identifier.urihttp://hdl.handle.net/10451/51496
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationGLYCINERGIC NEUROTRANSMISSION IN RAT HIPPOCAMPUS: A ROLE IN EPILEPTIC STATUS
dc.relationMODULATION OF THE BIDIRECTIONAL COMMUNICATION BETWEEN NEURONS AND ASTROCYTES AT THE SYNAPSE: INFLUENCE OF BDNF AND P2 RECEPTORS
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/neurochemistry-internationalpt_PT
dc.subjectGlycine transporter 2pt_PT
dc.subjectHippocampuspt_PT
dc.subjectNeurotrophic factorspt_PT
dc.subjectSynaptosomespt_PT
dc.titleBDNF modulates glycine uptake in hippocampal synaptosomes by decreasing membrane insertion of glycine transporter 2pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleGLYCINERGIC NEUROTRANSMISSION IN RAT HIPPOCAMPUS: A ROLE IN EPILEPTIC STATUS
oaire.awardTitleMODULATION OF THE BIDIRECTIONAL COMMUNICATION BETWEEN NEURONS AND ASTROCYTES AT THE SYNAPSE: INFLUENCE OF BDNF AND P2 RECEPTORS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F62831%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F81627%2F2011/PT
oaire.citation.endPage102pt_PT
oaire.citation.startPage94pt_PT
oaire.citation.titleNeurochemistry Internationalpt_PT
oaire.citation.volume99pt_PT
person.familyNamePedro Aroeira
person.familyNameHenriques Vaz
person.familyNameSebastião
person.familyNameValente
person.givenNameRita Isabel
person.givenNameSandra Cristina
person.givenNameAna M
person.givenNameCláudia
person.identifier.ciencia-id7E19-66A0-0A60
person.identifier.ciencia-id0E1C-952D-61BE
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.ciencia-idBD1B-6720-D51D
person.identifier.orcid0000-0002-6886-3334
person.identifier.orcid0000-0003-4258-9397
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.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.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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