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EMBO J ; 36(22): 3292-3308, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28963396

RESUMO

Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here, we show that in contrast to healthy adult and inflammation-activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c+ microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration, and differentiation. These cells are the major source of insulin-like growth factor 1, and its selective depletion from CD11c+ microglia leads to impairment of primary myelination. CD11c-targeted toxin regimens induced a selective transcriptional response in neonates, distinct from adult microglia. CD11c+ microglia are also found in clusters of repopulating microglia after experimental ablation and in neuroinflammation in adult mice, but despite some similarities, they do not recapitulate neonatal microglial characteristics. We therefore identify a unique phenotype of neonatal microglia that deliver signals necessary for myelination and neurogenesis.


Assuntos
Encéfalo/citologia , Encéfalo/embriologia , Microglia/metabolismo , Bainha de Mielina/metabolismo , Neurogênese , Envelhecimento/genética , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Encéfalo/ultraestrutura , Antígeno CD11c/metabolismo , Agregação Celular , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/patologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos Endogâmicos C57BL , Placa Neural/metabolismo , Regulação para Cima/genética
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