Autor(es):
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.
Data: 2023
Identificador Persistente: http://hdl.handle.net/10400.22/25126
Origem: Repositório Científico do Instituto Politécnico do Porto
Assunto(s): Microglia Rac1; RhoGTPases; Synaptic plasticity; Glia-neuron interactions; Proteomics; RNA seq; Environmental enrichment; Cognition
Descrição
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.
