Identification of a choroid plexus vascular barrier closing during intestinal inflammation.

Abstract

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/β-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.

• Authors: Sara Carloni, Alice Bertocchi, Sara Mancinelli, Martina Bellini, Marco Erreni, Antonella Borreca, Daniele Braga, Silvia Giugliano, Alessandro M Mozzarelli, Daria Manganaro, Daniel Fernandez Perez, Federico Colombo, Antonio Di Sabatino, Diego Pasini, Giuseppe Penna, Michela Matteoli, Simona Lodato, Maria Rescigno
• Journal: Science (New York, N.Y.) (Science) Vol. 374 Issue 6566 Pg. 439-448 (Oct 22 2021) ISSN: 1095-9203 [Electronic] United States
• PMID: 34672740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dextrans
• Lipopolysaccharides
• Wnt Proteins
• beta Catenin

Topics

• Animals
• Anxiety (etiology, physiopathology)
• Blood-Brain Barrier (pathology)
• Choroid Plexus (blood supply, physiopathology)
• Colitis, Ulcerative (complications, physiopathology, psychology)
• Dextrans
• Disease Models, Animal
• Humans
• Intestines (physiopathology)
• Lipopolysaccharides
• Memory Disorders (etiology, physiopathology)
• Memory, Short-Term
• Mice
• Mice, Inbred C57BL
• Microglia (pathology)
• Signal Transduction
• Tight Junctions (pathology)
• Wnt Proteins (metabolism)
• beta Catenin (metabolism)