Identification of a choroid plexus vascular barrier closing during intestinal inflammation

被引：192

作者：

Carloni, Sara ^{[1
,2
]}

Bertocchi, Alice ^{[2
]}

Mancinelli, Sara ^{[1
,2
]}

Bellini, Martina ^{[1
,2
]}

Erreni, Marco ^{[1
,2
]}

Borreca, Antonella ^{[2
,3
]}

Braga, Daniele ^{[2
]}

Giugliano, Silvia ^{[2
]}

Mozzarelli, Alessandro M. ^{[1
,2
]}

Manganaro, Daria ^{[5
]}

Perez, Daniel Fernandez ^{[5
]}

Colombo, Federico ^{[2
]}

Di Sabatino, Antonio ^{[4
]}

Pasini, Diego ^{[5
,6
]}

Penna, Giuseppe ^{[2
]}

Matteoli, Michela ^{[2
,3
]}

Lodato, Simona ^{[1
,2
]}

Rescigno, Maria ^{[1
,2
]}

机构：

[1] Humanitas Univ, Dept Biomed Sci, I-20072 Milan, Italy

[2] IRCCS Humanitas Res Hosp, I-20089 Milan, Italy

[3] Humanitas Res Hosp, Inst Neurosci, Natl Res Council, I-20089 Milan, Italy

[4] Univ Pavia, San Matteo Hosp Fdn, Dept Internal Med, I-27100 Pavia, Italy

[5] IRCCS, Dept Expt Oncol, European Inst Oncol IEO, I-20139 Milan, Italy

[6] Univ Milan, Dept Hlth Sci, I-20142 Milan, Italy

来源：

SCIENCE | 2021年 / 374卷 / 6566期

基金：

欧洲研究理事会;

关键词：

ENDOTHELIAL-CELLS; GENE-EXPRESSION; BRAIN-BARRIER; GUT; MICE; PHYSIOLOGY; DIAPHRAGMS; PATHWAY; DISEASE; ANXIETY;

D O I：

10.1126/science.abc6108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Up to 40% of patients with inflammatory bowel disease present with psychosocial disturbances. We previously identified a gut vascular barrier that controls the dissemination of bacteria from the intestine to the liver. Here, we describe a vascular barrier in the brain choroid plexus (PVB) that is modulated in response to intestinal inflammation through bacteria-derived lipopolysaccharide. The inflammatory response induces PVB closure after gut vascular barrier opening by the up-regulation of the wingless-type, catenin-beta 1 (Wnt/beta-catenin) signaling pathway, rendering it inaccessible to large molecules. In a model of genetically driven closure of choroid plexus endothelial cells, we observed a deficit in short-term memory and anxiety-like behavior, suggesting that PVB closure may correlate with mental deficits. Inflammatory bowel disease-related mental symptoms may thus be the consequence of a deregulated gut-brain vascular axis.

引用

页码：439 / +

页数：62

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