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Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance

2023-12-26Journal article Open access
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dc.contributor.authorSocodato, Renato
dc.contributor.authorAlmeida, Tiago O.
dc.contributor.authorPortugal, Camila C.
dc.contributor.authorSantos, Evelyn C.S.
dc.contributor.authorTedim-Moreira, Joana
dc.contributor.authorFerreira, João Galvão
dc.contributor.authorCanedo, Teresa
dc.contributor.authorBaptista, Filipa I.
dc.contributor.authorMagalhães, Ana
dc.contributor.authorAmbrósio, António F.
dc.contributor.authorBrakebusch, Cord
dc.contributor.authorRubinstein, Boris
dc.contributor.authorMoreira, Irina S.
dc.contributor.authorSummavielle, Teresa
dc.contributor.authorPinto, Inês Mendes
dc.contributor.authorRelvas, João B.
dc.date.accessioned2024-03-05T13:12:17Z
dc.date.available2024-03-05T13:12:17Z
dc.date.issued2023-12-26
dc.description.abstractMicroglia, the largest population of brain immune cells, continuously interact with synapses to maintain brain homeostasis. In this study, we use conditional cell-specific gene targeting in mice with multi-omics approaches and demonstrate that the RhoGTPase Rac1 is an essential requirement for microglia to sense and interpret the brain microenvironment. This is crucial for microglia-synapse crosstalk that drives experience-dependent plasticity, a fundamental brain property impaired in several neuropsychiatric disorders. Phosphoproteomics profiling detects a large modulation of RhoGTPase signaling, predominantly of Rac1, in microglia of mice exposed to an environmental enrichment protocol known to induce experience-dependent brain plasticity and cognitive performance. Ablation of microglial Rac1 affects pathways involved in microglia-synapse communication, disrupts experience-dependent synaptic remodeling, and blocks the gains in learning, memory, and sociability induced by environmental enrichment. Our results reveal microglial Rac1 as a central regulator of pathways involved in the microglia-synapse crosstalk required for experience-dependent synaptic plasticity and cognitive performance.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSocodato, R., Almeida, T. O., Portugal, C. C., Santos, E. C. S., Tedim-Moreira, J., Galvão-Ferreira, J., Canedo, T., Baptista, F. I., Magalhães, A., Ambrósio, A. F., Brakebusch, C., Rubinstein, B., Moreira, I. S., Summavielle, T., Pinto, I. M., & Relvas, J. B. (2023). Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance. Cell Reports, 42(12), 113447. https://doi.org/10.1016/j.celrep.2023.113447pt_PT
dc.identifier.doi10.1016/j.celrep.2023.113447pt_PT
dc.identifier.eissn2211-1247
dc.identifier.urihttp://hdl.handle.net/10400.22/25126
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherCell Presspt_PT
dc.relationPTDC/MED-NEU/1677/2021pt_PT
dc.relationPTDC/SAU-TOX/0067/2021 and 2022.03699.CEECINDpt_PT
dc.relation600375pt_PT
dc.relationSFRH/BD/147981/2019pt_PT
dc.relationUI/BD/151552/2021pt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S2211124723014596pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectMicroglia Rac1pt_PT
dc.subjectRhoGTPasespt_PT
dc.subjectSynaptic plasticitypt_PT
dc.subjectGlia-neuron interactionspt_PT
dc.subjectProteomicspt_PT
dc.subjectRNA seqpt_PT
dc.subjectEnvironmental enrichmentpt_PT
dc.subjectCognitionpt_PT
dc.titleMicroglial Rac1 is essential for experience-dependent brain plasticity and cognitive performancept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage27pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleCell Reportspt_PT
oaire.citation.volume42 (12)pt_PT
person.familyNameSummavielle
person.givenNameTeresa
person.identifier677706
person.identifier.ciencia-idC41E-0816-5C85
person.identifier.orcid0000-0003-2548-6281
person.identifier.ridC-9776-2012
person.identifier.scopus-author-id6603092949
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication207ee2de-85a0-4144-9e7e-b376c600e065
relation.isAuthorOfPublication.latestForDiscovery207ee2de-85a0-4144-9e7e-b376c600e065

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