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dc.creatorMcKim, Daniel B.
dc.creatorWeber, Michael D.
dc.creatorNiraula, Anzela
dc.creatorSawicki, Caroline M.
dc.creatorLiu, X.
dc.creatorJarrett, Brant L.
dc.creatorRamírez Chan, Karol Gabriela
dc.creatorWang, Yufen
dc.creatorRoeth, R. M.
dc.creatorSucaldito, A. D.
dc.creatorSobol, Carly G.
dc.creatorQuan, Ning
dc.creatorSheridan, John F.
dc.creatorGodbout, Jonathan P.
dc.date.accessioned2020-06-24T21:32:34Z
dc.date.available2020-06-24T21:32:34Z
dc.date.issued2017-04-04
dc.identifier.citationhttps://www.nature.com/articles/mp201764
dc.identifier.issn1476-5578
dc.identifier.urihttps://hdl.handle.net/10669/81202
dc.description.abstractPsychosocial stress contributes to the development of anxiety and depression. Recent clinical studies have reported increased inflammatory leukocytes in circulation of individuals with stress-related psychiatric disorders. Parallel to this, our work in mice shows that social stress causes release of inflammatory monocytes into circulation. In addition, social stress caused the development of prolonged anxiety that was dependent on inflammatory monocytes in the brain. Therefore, we hypothesize that chronic stress drives the production of inflammatory monocytes that are actively recruited to the brain by microglia, and these monocytes augment neuroinflammatory signaling and prolong anxiety. Here we show that repeated social defeat stress in mice activated threat appraisal centers in the brain that spatially coincided with microglial activation and endothelial facilitation of monocyte recruitment. Moreover, microglial depletion with a CSF1R antagonist prior to stress prevented the recruitment of monocytes to the brain and abrogated the development of anxiety. Cell-specific transcriptional profiling revealed that microglia selectively enhanced CCL2 expression, while monocytes expressed the pro-inflammatory cytokine interleukin-1β (IL-1β). Consistent with these profiles, the recruited inflammatory monocytes with stress adhered to IL-1R1+ neurovascular endothelial cells and this interaction was blocked by microglial depletion. Furthermore, disruption of IL-1β signaling by caspase-1KO specifically within bone marrow-derived cells revealed that monocytes promoted anxiogenesis through stimulation of neurovascular IL-1R1 by IL-1β. Collectively, the development of anxiety during stress was caused by microglial recruitment of IL-1β-producing monocytes, which stimulated brain endothelial IL-1R1. Thus, monocyte IL-1β production represents a novel mechanism that underlies behavioral complications associated with stress-related psychiatric disorders.es_ES
dc.description.sponsorshipNational Institute of Health (NIMH) grants R01-MH-093473es_ES
dc.description.sponsorshipNational Institute of Health (NIMH) grants R01-MH093472es_ES
dc.description.sponsorshipNIDCR Training Grant T32-DE014320es_ES
dc.description.sponsorshipF31-MH-109234es_ES
dc.language.isoen_USes_ES
dc.sourceMolecular Psychiatry, 23, 1421-1431es_ES
dc.subjectstresses_ES
dc.subjectanxietyes_ES
dc.subjectdepressiones_ES
dc.titleMicroglial recruitment of IL-1β-producing monocytes to brain endothelium causes stress-induced anxietyes_ES
dc.typeartículo científico
dc.identifier.doi10.1038/mp.2017.64
dc.description.procedenceUCR::Vicerrectoría de Docencia::Salud::Facultad de Odontologíaes_ES
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Neurociencias (CIN)es_ES


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