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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance. / Socodato, Renato; Almeida, Tiago O.; Portugal, Camila C.; Santos, Evelyn C.S.; Tedim-Moreira, Joana; Galvão-Ferreira, João; 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.

In: Cell Reports, Vol. 42, No. 12, 113447, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Socodato, R, Almeida, TO, Portugal, CC, Santos, ECS, Tedim-Moreira, J, Galvão-Ferreira, J, Canedo, T, Baptista, FI, Magalhães, A, Ambrósio, AF, Brakebusch, C, Rubinstein, B, Moreira, IS, Summavielle, T, Pinto, IM & Relvas, JB 2023, 'Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance', Cell Reports, vol. 42, no. 12, 113447. https://doi.org/10.1016/j.celrep.2023.113447

APA

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

Vancouver

Socodato R, Almeida TO, Portugal CC, Santos ECS, Tedim-Moreira J, Galvão-Ferreira J et al. Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance. Cell Reports. 2023;42(12). 113447. https://doi.org/10.1016/j.celrep.2023.113447

Author

Socodato, Renato ; Almeida, Tiago O. ; Portugal, Camila C. ; Santos, Evelyn C.S. ; Tedim-Moreira, Joana ; Galvão-Ferreira, João ; 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. / Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance. In: Cell Reports. 2023 ; Vol. 42, No. 12.

Bibtex

@article{5ca9ef2e74554bf4b825bc05e8c65767,
title = "Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance",
abstract = "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.",
keywords = "cognition, CP: Cell biology, CP: Neuroscience, environmental enrichment, glia-neuron interactions, microglia, proteomics, Rac1, RhoGTPases, RNAseq, synaptic plasticity",
author = "Renato Socodato and Almeida, {Tiago O.} and Portugal, {Camila C.} and Santos, {Evelyn C.S.} and Joana Tedim-Moreira and Jo{\~a}o Galv{\~a}o-Ferreira and Teresa Canedo and Baptista, {Filipa I.} and Ana Magalh{\~a}es and Ambr{\'o}sio, {Ant{\'o}nio F.} and Cord Brakebusch and Boris Rubinstein and Moreira, {Irina S.} and Teresa Summavielle and Pinto, {In{\^e}s Mendes} and Relvas, {Jo{\~a}o B.}",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
doi = "10.1016/j.celrep.2023.113447",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",

}

RIS

TY - JOUR

T1 - Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance

AU - Socodato, Renato

AU - Almeida, Tiago O.

AU - Portugal, Camila C.

AU - Santos, Evelyn C.S.

AU - Tedim-Moreira, Joana

AU - Galvão-Ferreira, João

AU - Canedo, Teresa

AU - Baptista, Filipa I.

AU - Magalhães, Ana

AU - Ambrósio, António F.

AU - Brakebusch, Cord

AU - Rubinstein, Boris

AU - Moreira, Irina S.

AU - Summavielle, Teresa

AU - Pinto, Inês Mendes

AU - Relvas, João B.

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - cognition

KW - CP: Cell biology

KW - CP: Neuroscience

KW - environmental enrichment

KW - glia-neuron interactions

KW - microglia

KW - proteomics

KW - Rac1

KW - RhoGTPases

KW - RNAseq

KW - synaptic plasticity

U2 - 10.1016/j.celrep.2023.113447

DO - 10.1016/j.celrep.2023.113447

M3 - Journal article

C2 - 37980559

AN - SCOPUS:85177068902

VL - 42

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 12

M1 - 113447

ER -

ID: 374454604