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Triiodothyronine modulates neuronal plasticity mechanisms to enhance functional outcome after stroke

2019-12-21Journal article Open access
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dc.contributor.authorTalhada, Daniela
dc.contributor.authorFeiteiro, Joana
dc.contributor.authorCosta, Ana Raquel
dc.contributor.authorTalhada, Tiago
dc.contributor.authorCairrão, Elisa
dc.contributor.authorWieloch, Tadeusz
dc.contributor.authorEnglund, Elisabet
dc.contributor.authorSantos, Cecilia Reis
dc.contributor.authorGonçalves, Isabel
dc.contributor.authorRuscher, Karsten
dc.date.accessioned2020-03-02T10:51:46Z
dc.date.available2020-03-02T10:51:46Z
dc.date.issued2019-12-21
dc.description.abstractThe development of new therapeutic approaches for stroke patients requires a detailed understanding of the mechanisms that enhance recovery of lost neurological functions. The efficacy to enhance homeostatic mechanisms during the first weeks after stroke will influence functional outcome. Thyroid hormones (TH) are essential regulators of neuronal plasticity, however, their role in recovery related mechanisms of neuronal plasticity after stroke remains unknown. This study addresses important findings of 3,5,3'-triiodo-L-thyronine (T3) in the regulation of homeostatic mechanisms that adjust excitability - inhibition ratio in the post-ischemic brain. This is valid during the first 2 weeks after experimental stroke induced by photothrombosis (PT) and in cultured neurons subjected to an in vitro model of acute cerebral ischemia. In the human post-stroke brain, we assessed the expression pattern of TH receptors (TR) protein levels, important for mediating T3 actions.Our results show that T3 modulates several plasticity mechanisms that may operate on different temporal and spatial scales as compensatory mechanisms to assure appropriate synaptic neurotransmission. We have shown in vivo that long-term administration of T3 after PT significantly (1) enhances lost sensorimotor function; (2) increases levels of synaptotagmin 1&2 and levels of the post-synaptic GluR2 subunit in AMPA receptors in the peri-infarct area; (3) increases dendritic spine density in the peri-infarct and contralateral region and (4) decreases tonic GABAergic signaling in the peri-infarct area by a reduced number of parvalbumin+ / c-fos+ neurons and glutamic acid decarboxylase 65/67 levels. In addition, we have shown that T3 modulates in vitro neuron membrane properties with the balance of inward glutamate ligand-gated channels currents and decreases synaptotagmin levels in conditions of deprived oxygen and glucose. Interestingly, we found increased levels of TRβ1 in the infarct core of post-mortem human stroke patients, which mediate T3 actions. Summarizing, our data identify T3 as a potential key therapeutic agent to enhance recovery of lost neurological functions after ischemic stroke.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1186/s40478-019-0866-4pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/9648
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationHealth Sciences Research Centre
dc.relationThe role of transthyretin and thyroid hormones on functional recovery after experimental stroke
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectIschemiapt_PT
dc.subjectPhotothrombosispt_PT
dc.subjectRecoverypt_PT
dc.subjectStrokept_PT
dc.subjectThyroid hormonespt_PT
dc.subjectThyroid hormone receptorspt_PT
dc.titleTriiodothyronine modulates neuronal plasticity mechanisms to enhance functional outcome after strokept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleHealth Sciences Research Centre
oaire.awardTitleThe role of transthyretin and thyroid hormones on functional recovery after experimental stroke
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F00709%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F104679%2F2014/PT
oaire.citation.issue1pt_PT
oaire.citation.startPage216pt_PT
oaire.citation.titleActa Neuropathologica Communicationspt_PT
oaire.citation.volume7pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameTalhada
person.familyNameOliveira Feiteiro
person.familyNameCosta
person.familyNameCairrao Rodrigues Oliveira
person.familyNameWieloch
person.familyNameEnglund
person.familyNameSANTOS
person.familyNameTheriaga Mendes Varanda Gonçalves
person.familyNameRuscher
person.givenNameDaniela
person.givenNameJoana Rita
person.givenNameAna Raquel
person.givenNameMaria Elisa
person.givenNameTadeusz
person.givenNameElisabet
person.givenNameCecília Reis Alves
person.givenNameIsabel Maria
person.givenNameKarsten
person.identifier746983
person.identifierAAB-1164-2020
person.identifier.ciencia-id1D17-E1B2-A506
person.identifier.ciencia-id4315-0AE9-C7BB
person.identifier.ciencia-id7D10-8378-9ABD
person.identifier.ciencia-id0611-71B8-191E
person.identifier.ciencia-id761A-7ED2-D68F
person.identifier.ciencia-idD916-0E13-ECB8
person.identifier.orcid0000-0002-5424-1438
person.identifier.orcid0000-0002-4487-0484
person.identifier.orcid0000-0002-9673-4337
person.identifier.orcid0000-0002-4823-5701
person.identifier.orcid0000-0002-7669-2520
person.identifier.orcid0000-0002-2708-2443
person.identifier.orcid0000-0001-6074-7825
person.identifier.orcid0000-0002-4384-8197
person.identifier.orcid0000-0001-7211-2499
person.identifier.scopus-author-id55855123200
person.identifier.scopus-author-idScopus Author ID: 23476537500
person.identifier.scopus-author-id7004584850
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.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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