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

Locking down access to the brain
Inflammatory bowel disease is best known for intestinal symptoms but can also cause a variety of extraintestinal manifestations in other organs. It can also be associated with cognitive and psychiatric effects, including anxiety and depression. Using mouse models of intestinal inflammation, Carloni et al. uncovered a potential pathogenic link between these aspects of inflammatory bowel disease.

The inflammatory process causes the gut vascular barrier to become more permeable, resulting in the spread of inflammation beyond the intestine, while the vascular barrier in the choroid plexus shuts down, helping protect the brain from inflammation but also potentially impairing communication between organs and impairing some brain functions. —YN

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.