title: Deletion of astroglial connexins weakens the blood-brain barrier.
abstract: Astrocytes, the most prominent glial cell type in the brain, send specialized processes named endfeet, which enwrap blood vessels and express a large molecular repertoire dedicated to the physiology of the vascular system. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction protein connexins 43 and 30 (Cx43 and Cx30) allowing for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. The contribution of astroglial connexins to the physiology of the brain vascular system has never been addressed. Here, we show that Cx43 and Cx30 expression at the level of perivascular endfeet starts from postnatal days 2 and 12 and is fully mature at postnatal days 15 and 20, respectively, indicating that astroglial perivascular connectivity occurs and develops during postnatal blood-brain barrier (BBB) maturation. We demonstrate that mice lacking Cx30 and Cx43 in GFAP (glial fibrillary acidic protein)-positive cells display astrocyte endfeet edema and a partial loss of the astroglial water channel aquaporin-4 and β-dystroglycan, a transmembrane receptor anchoring astrocyte endfeet to the perivascular basal lamina. Furthermore, the absence of astroglial connexins weakens the BBB, which opens upon increased hydrostatic vascular pressure and shear stress. These results demonstrate that astroglial connexins are necessary to maintain BBB integrity.
authors.affiliation: Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Collège de France, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Ezan
authors.forename: Pascal
authors.initials: P
authors.lastname: André
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cisternino
authors.forename: Bruno
authors.initials: B
authors.lastname: Saubaméa
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Boulay
authors.forename: Suzette
authors.initials: S
authors.lastname: Doutremer
authors.forename: Marie-Annick
authors.initials: MA
authors.lastname: Thomas
authors.forename: Nicole
authors.initials: N
authors.lastname: Quenech'du
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
authors.forename: Martine
authors.initials: M
authors.lastname: Cohen-Salmon
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D002560:Cerebrovascular Circulation / Q000235:genetics; D000075302:Connexin 30; D018031:Connexin 43 / Q000235:genetics / Q000502:physiology*; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D010477:Perfusion
chemical_list: D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; C100629:Gjb6 protein, mouse