Evidence of a Myenteric Plexus Barrier and Its Macrophage-Dependent Degradation During Murine Colitis: Implications in Enteric NeuroinflammationSummary

Background & Aims: Neuroinflammation in the gut is associated with many gastrointestinal (GI) diseases, including inflammatory bowel disease. In the brain, neuroinflammatory conditions are associated with blood-brain barrier (BBB) disruption and subsequent neuronal injury. We sought to deter...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	David Dora, Szilamer Ferenczi, Rhian Stavely, Viktoria E. Toth, Zoltan V. Varga, Tamas Kovacs, Ildiko Bodi, Ryo Hotta, Krisztina J. Kovacs, Allan M. Goldstein, Nandor Nagy
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Barrier Enteric Ganglion Macrophage ECM Intraganglionic Macrophage Colitis Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/b9e37b6203c345f9b54c75273c761468
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b9e37b6203c345f9b54c75273c761468
record_format	dspace
spelling	oai:doaj.org-article:b9e37b6203c345f9b54c75273c7614682021-11-12T04:38:53ZEvidence of a Myenteric Plexus Barrier and Its Macrophage-Dependent Degradation During Murine Colitis: Implications in Enteric NeuroinflammationSummary2352-345X10.1016/j.jcmgh.2021.07.003https://doaj.org/article/b9e37b6203c345f9b54c75273c7614682021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352345X21001442https://doaj.org/toc/2352-345XBackground & Aims: Neuroinflammation in the gut is associated with many gastrointestinal (GI) diseases, including inflammatory bowel disease. In the brain, neuroinflammatory conditions are associated with blood-brain barrier (BBB) disruption and subsequent neuronal injury. We sought to determine whether the enteric nervous system is similarly protected by a physical barrier and whether that barrier is disrupted in colitis. Methods: Confocal and electron microscopy were used to characterize myenteric plexus structure, and FITC-dextran assays were used to assess for presence of a barrier. Colitis was induced with dextran sulfate sodium, with co-administration of liposome-encapsulated clodronate to deplete macrophages. Results: We identified a blood-myenteric barrier (BMB) consisting of extracellular matrix proteins (agrin and collagen-4) and glial end-feet, reminiscent of the BBB, surrounded by a collagen-rich periganglionic space. The BMB is impermeable to the passive movement of 4 kDa FITC-dextran particles. A population of macrophages is present within enteric ganglia (intraganglionic macrophages [IGMs]) and exhibits a distinct morphology from muscularis macrophages, with extensive cytoplasmic vacuolization and mitochondrial swelling but without signs of apoptosis. IGMs can penetrate the BMB in physiological conditions and establish direct contact with neurons and glia. Dextran sulfate sodium-induced colitis leads to BMB disruption, loss of its barrier integrity, and increased numbers of IGMs in a macrophage-dependent process. Conclusions: In intestinal inflammation, macrophage-mediated degradation of the BMB disrupts its physiological barrier function, eliminates the separation of the intra- and extra-ganglionic compartments, and allows inflammatory stimuli to access the myenteric plexus. This suggests a potential mechanism for the onset of neuroinflammation in colitis and other GI pathologies with acquired enteric neuronal dysfunction.David DoraSzilamer FerencziRhian StavelyViktoria E. TothZoltan V. VargaTamas KovacsIldiko BodiRyo HottaKrisztina J. KovacsAllan M. GoldsteinNandor NagyElsevierarticleBarrierEnteric GanglionMacrophageECMIntraganglionic MacrophageColitisDiseases of the digestive system. GastroenterologyRC799-869ENCellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 5, Pp 1617-1641 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Barrier Enteric Ganglion Macrophage ECM Intraganglionic Macrophage Colitis Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Barrier Enteric Ganglion Macrophage ECM Intraganglionic Macrophage Colitis Diseases of the digestive system. Gastroenterology RC799-869 David Dora Szilamer Ferenczi Rhian Stavely Viktoria E. Toth Zoltan V. Varga Tamas Kovacs Ildiko Bodi Ryo Hotta Krisztina J. Kovacs Allan M. Goldstein Nandor Nagy Evidence of a Myenteric Plexus Barrier and Its Macrophage-Dependent Degradation During Murine Colitis: Implications in Enteric NeuroinflammationSummary
description	Background & Aims: Neuroinflammation in the gut is associated with many gastrointestinal (GI) diseases, including inflammatory bowel disease. In the brain, neuroinflammatory conditions are associated with blood-brain barrier (BBB) disruption and subsequent neuronal injury. We sought to determine whether the enteric nervous system is similarly protected by a physical barrier and whether that barrier is disrupted in colitis. Methods: Confocal and electron microscopy were used to characterize myenteric plexus structure, and FITC-dextran assays were used to assess for presence of a barrier. Colitis was induced with dextran sulfate sodium, with co-administration of liposome-encapsulated clodronate to deplete macrophages. Results: We identified a blood-myenteric barrier (BMB) consisting of extracellular matrix proteins (agrin and collagen-4) and glial end-feet, reminiscent of the BBB, surrounded by a collagen-rich periganglionic space. The BMB is impermeable to the passive movement of 4 kDa FITC-dextran particles. A population of macrophages is present within enteric ganglia (intraganglionic macrophages [IGMs]) and exhibits a distinct morphology from muscularis macrophages, with extensive cytoplasmic vacuolization and mitochondrial swelling but without signs of apoptosis. IGMs can penetrate the BMB in physiological conditions and establish direct contact with neurons and glia. Dextran sulfate sodium-induced colitis leads to BMB disruption, loss of its barrier integrity, and increased numbers of IGMs in a macrophage-dependent process. Conclusions: In intestinal inflammation, macrophage-mediated degradation of the BMB disrupts its physiological barrier function, eliminates the separation of the intra- and extra-ganglionic compartments, and allows inflammatory stimuli to access the myenteric plexus. This suggests a potential mechanism for the onset of neuroinflammation in colitis and other GI pathologies with acquired enteric neuronal dysfunction.
format	article
author	David Dora Szilamer Ferenczi Rhian Stavely Viktoria E. Toth Zoltan V. Varga Tamas Kovacs Ildiko Bodi Ryo Hotta Krisztina J. Kovacs Allan M. Goldstein Nandor Nagy
author_facet	David Dora Szilamer Ferenczi Rhian Stavely Viktoria E. Toth Zoltan V. Varga Tamas Kovacs Ildiko Bodi Ryo Hotta Krisztina J. Kovacs Allan M. Goldstein Nandor Nagy
author_sort	David Dora
title	Evidence of a Myenteric Plexus Barrier and Its Macrophage-Dependent Degradation During Murine Colitis: Implications in Enteric NeuroinflammationSummary
title_short	Evidence of a Myenteric Plexus Barrier and Its Macrophage-Dependent Degradation During Murine Colitis: Implications in Enteric NeuroinflammationSummary
title_full	Evidence of a Myenteric Plexus Barrier and Its Macrophage-Dependent Degradation During Murine Colitis: Implications in Enteric NeuroinflammationSummary
title_fullStr	Evidence of a Myenteric Plexus Barrier and Its Macrophage-Dependent Degradation During Murine Colitis: Implications in Enteric NeuroinflammationSummary
title_full_unstemmed	Evidence of a Myenteric Plexus Barrier and Its Macrophage-Dependent Degradation During Murine Colitis: Implications in Enteric NeuroinflammationSummary
title_sort	evidence of a myenteric plexus barrier and its macrophage-dependent degradation during murine colitis: implications in enteric neuroinflammationsummary
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/b9e37b6203c345f9b54c75273c761468
work_keys_str_mv	AT daviddora evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT szilamerferenczi evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT rhianstavely evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT viktoriaetoth evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT zoltanvvarga evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT tamaskovacs evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT ildikobodi evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT ryohotta evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT krisztinajkovacs evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT allanmgoldstein evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary AT nandornagy evidenceofamyentericplexusbarrieranditsmacrophagedependentdegradationduringmurinecolitisimplicationsinentericneuroinflammationsummary
_version_	1718431254378971136

Evidence of a Myenteric Plexus Barrier and Its Macrophage-Dependent Degradation During Murine Colitis: Implications in Enteric NeuroinflammationSummary

Ejemplares similares