期刊
SCIENCE
卷 374, 期 6566, 页码 439-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abc6108
关键词
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资金
- European Research Council [615735]
- Italian Foundation for Cancer Research [AIRC IG 22026, 21147, 22757]
- Fondazione CARIPLO [2019-1785]
- PRIN (Ministero dell'Istruzione dell'Universita e della Ricerca) [2017A9MK4R]
- FISM [2019/R-Single/032]
- AIRC/FIRC within the PhD program of the European School of Molecular Medicine (SEMM)
- European Research Council (ERC) [615735] Funding Source: European Research Council (ERC)
The passage discusses the presence of psychosocial disturbances in up to 40% of patients with inflammatory bowel disease, and identifies the potential role of a deregulated gut-brain vascular axis in causing mental deficits in these individuals.
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.
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