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

Detalhes bibliográficos
Autor(a) principal: Socodato, Renato
Data de Publicação: 2023
Outros Autores: Almeida, Tiago O., Portugal, Camila C., Santos, Evelyn C.S., Tedim-Moreira, Joana, Ferreira, João Galvão, Canedo, Teresa, Baptista, Filipa I., Magalhães, Ana, Ambrósio, António F., Brakebusch, Cord, Rubinstein, Boris, Moreira, Irina S., Summavielle, Teresa, Pinto, Inês Mendes, Relvas, João B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.22/25126
Resumo: Microglia, 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.
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spelling Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performanceMicroglia Rac1RhoGTPasesSynaptic plasticityGlia-neuron interactionsProteomicsRNA seqEnvironmental enrichmentCognitionMicroglia, 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.Cell PressRepositório Científico do Instituto Politécnico do PortoSocodato, RenatoAlmeida, Tiago O.Portugal, Camila C.Santos, Evelyn C.S.Tedim-Moreira, JoanaFerreira, João GalvãoCanedo, TeresaBaptista, Filipa I.Magalhães, AnaAmbrósio, António F.Brakebusch, CordRubinstein, BorisMoreira, Irina S.Summavielle, TeresaPinto, Inês MendesRelvas, João B.2024-03-05T13:12:17Z2023-12-262023-12-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.22/25126engSocodato, 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.2023.11344710.1016/j.celrep.2023.1134472211-1247info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-13T01:48:32Zoai:recipp.ipp.pt:10400.22/25126Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:13:27.635774Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
title Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
spellingShingle Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
Socodato, Renato
Microglia Rac1
RhoGTPases
Synaptic plasticity
Glia-neuron interactions
Proteomics
RNA seq
Environmental enrichment
Cognition
title_short Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
title_full Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
title_fullStr Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
title_full_unstemmed Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
title_sort Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
author Socodato, Renato
author_facet Socodato, Renato
Almeida, Tiago O.
Portugal, Camila C.
Santos, Evelyn C.S.
Tedim-Moreira, Joana
Ferreira, João Galvão
Canedo, Teresa
Baptista, Filipa I.
Magalhães, Ana
Ambrósio, António F.
Brakebusch, Cord
Rubinstein, Boris
Moreira, Irina S.
Summavielle, Teresa
Pinto, Inês Mendes
Relvas, João B.
author_role author
author2 Almeida, Tiago O.
Portugal, Camila C.
Santos, Evelyn C.S.
Tedim-Moreira, Joana
Ferreira, João Galvão
Canedo, Teresa
Baptista, Filipa I.
Magalhães, Ana
Ambrósio, António F.
Brakebusch, Cord
Rubinstein, Boris
Moreira, Irina S.
Summavielle, Teresa
Pinto, Inês Mendes
Relvas, João B.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Politécnico do Porto
dc.contributor.author.fl_str_mv Socodato, Renato
Almeida, Tiago O.
Portugal, Camila C.
Santos, Evelyn C.S.
Tedim-Moreira, Joana
Ferreira, João Galvão
Canedo, Teresa
Baptista, Filipa I.
Magalhães, Ana
Ambrósio, António F.
Brakebusch, Cord
Rubinstein, Boris
Moreira, Irina S.
Summavielle, Teresa
Pinto, Inês Mendes
Relvas, João B.
dc.subject.por.fl_str_mv Microglia Rac1
RhoGTPases
Synaptic plasticity
Glia-neuron interactions
Proteomics
RNA seq
Environmental enrichment
Cognition
topic Microglia Rac1
RhoGTPases
Synaptic plasticity
Glia-neuron interactions
Proteomics
RNA seq
Environmental enrichment
Cognition
description Microglia, 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.
publishDate 2023
dc.date.none.fl_str_mv 2023-12-26
2023-12-26T00:00:00Z
2024-03-05T13:12:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.22/25126
url http://hdl.handle.net/10400.22/25126
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Socodato, 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.2023.113447
10.1016/j.celrep.2023.113447
2211-1247
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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