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/b-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.

Identification of a choroid plexus vascular barrier closing during intestinal inflammation / S. Carloni, A. Bertocchi, S. Mancinelli, M. Bellini, M. Erreni, A. Borreca, D. Braga, S. Giugliano, A.M. Mozzarelli, D. Manganaro, D.F. Perez, F. Colombo, A. Di Sabatino, D. Pasini, G. Penna, M. Matteoli, S. Lodato, M. Rescigno. - In: SCIENCE. - ISSN 0036-8075. - 374:6566(2021 Oct 22), pp. 439-448. [10.1126/science.abc6108]

Identification of a choroid plexus vascular barrier closing during intestinal inflammation

S. Carloni
Primo
;
A. Bertocchi
Secondo
;
M. Erreni;D. Braga;D. Pasini;M. Matteoli;
2021

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/b-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.
Settore BIO/11 - Biologia Molecolare
22-ott-2021
Article (author)
File in questo prodotto:
File Dimensione Formato  
science.abc6108.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 2.19 MB
Formato Adobe PDF
2.19 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/946615
Citazioni
  • ???jsp.display-item.citation.pmc??? 61
  • Scopus 108
  • ???jsp.display-item.citation.isi??? 99
social impact