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Nat Commun ; 12(1): 5289, 2021 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-34489419

RESUMEN

Microglia are brain-resident immune cells with a repertoire of functions in the brain. However, the extent of their interactions with the vasculature and potential regulation of vascular physiology has been insufficiently explored. Here, we document interactions between ramified CX3CR1 + myeloid cell somata and brain capillaries. We confirm that these cells are bona fide microglia by molecular, morphological and ultrastructural approaches. Then, we give a detailed spatio-temporal characterization of these capillary-associated microglia (CAMs) comparing them with parenchymal microglia (PCMs) in their morphological activities including during microglial depletion and repopulation. Molecularly, we identify P2RY12 receptors as a regulator of CAM interactions under the control of released purines from pannexin 1 (PANX1) channels. Furthermore, microglial elimination triggered capillary dilation, blood flow increase, and impaired vasodilation that were recapitulated in P2RY12-/- and PANX1-/- mice suggesting purines released through PANX1 channels play important roles in activating microglial P2RY12 receptors to regulate neurovascular structure and function.


Asunto(s)
Encéfalo/irrigación sanguínea , Conexinas/genética , Microglía/metabolismo , Células Mieloides/metabolismo , Proteínas del Tejido Nervioso/genética , Receptores Purinérgicos P2Y12/genética , Animales , Encéfalo/citología , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Receptor 1 de Quimiocinas CX3C/genética , Receptor 1 de Quimiocinas CX3C/metabolismo , Recuento de Células , Circulación Cerebrovascular/fisiología , Conexinas/deficiencia , Electrodos Implantados , Femenino , Regulación de la Expresión Génica , Genes Reporteros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Masculino , Ratones , Ratones Noqueados , Microglía/citología , Células Mieloides/citología , Proteínas del Tejido Nervioso/deficiencia , Neuroimagen/instrumentación , Neuroimagen/métodos , Receptores Purinérgicos P2Y12/deficiencia , Receptores Purinérgicos P2Y12/metabolismo , Vasodilatación/fisiología
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