title: Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain.
abstract: Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood-brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB.
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.|Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Furube
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mannari
authors.affiliation: Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okuda
authors.affiliation: Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors.forename: Kouko
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Wanaka
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan. smiyata@kit.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Miyata
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology*; D066280:Circumventricular Organs / Q000033:anatomy & histology / Q000098:blood supply* / Q000648:ultrastructure; D062507:Claudin-5 / Q000378:metabolism; D004058:Diffusion; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D062793:Occludin / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D062507:Claudin-5; D016650:Fluorescein-5-isothiocyanate; D062793:Occludin; D062826:Zonula Occludens-1 Protein; D000099152:Cadherin 5
keywords: Astrocyte; Blood–brain barrier; Mouse; Perivascular space; Tight junction; Vascular permeability