Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
In: Cell Reports, Jg. 42 (2023), Heft 12, S. 113447-
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Summary: 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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Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
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Autor/in / Beteiligte Person: | Socodato, Renato ; Almeida, Tiago O. ; Portugal, Camila C. ; Evelyn C.S. Santos ; 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 ; Inês Mendes Pinto ; Relvas, João B. |
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Zeitschrift: | Cell Reports, Jg. 42 (2023), Heft 12, S. 113447- |
Veröffentlichung: | Elsevier, 2023 |
Medientyp: | academicJournal |
ISSN: | 2211-1247 (print) |
DOI: | 10.1016/j.celrep.2023.113447 |
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