PMID- 26048259 OWN - NLM STAT- MEDLINE DCOM- 20161024 LR - 20161230 IS - 1432-0878 (Electronic) IS - 0302-766X (Linking) VI - 363 IP - 2 DP - 2016 Feb TI - Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain. PG - 497-511 LID - 10.1007/s00441-015-2207-7 [doi] AB - 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. FAU - Morita, Shoko AU - Morita S AD - Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan. AD - Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara, 634-8521, Japan. FAU - Furube, Eriko AU - Furube E AD - Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan. FAU - Mannari, Tetsuya AU - Mannari T AD - Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan. FAU - Okuda, Hiroaki AU - Okuda H AD - Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara, 634-8521, Japan. FAU - Tatsumi, Kouko AU - Tatsumi K AD - Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara, 634-8521, Japan. FAU - Wanaka, Akio AU - Wanaka A AD - Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara, 634-8521, Japan. FAU - Miyata, Seiji AU - Miyata S AD - Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan. smiyata@kit.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150606 PL - Germany TA - Cell Tissue Res JT - Cell and tissue research JID - 0417625 RN - 0 (Antigens, CD) RN - 0 (Cadherins) RN - 0 (Claudin-5) RN - 0 (Occludin) RN - 0 (Zonula Occludens-1 Protein) RN - 0 (cadherin 5) RN - I223NX31W9 (Fluorescein-5-isothiocyanate) SB - IM MH - Aging/*physiology MH - Animals MH - Antigens, CD/metabolism MH - Blood-Brain Barrier/*physiology MH - Cadherins/metabolism MH - Capillary Permeability/*physiology MH - Circumventricular Organs/anatomy & histology/*blood supply/ultrastructure MH - Claudin-5/metabolism MH - Diffusion MH - Fluorescein-5-isothiocyanate/metabolism MH - Male MH - Mice, Inbred C57BL MH - Models, Biological MH - Occludin/metabolism MH - Zonula Occludens-1 Protein/metabolism OTO - NOTNLM OT - Astrocyte OT - Blood-brain barrier OT - Mouse OT - Perivascular space OT - Tight junction OT - Vascular permeability EDAT- 2015/06/07 06:00 MHDA- 2016/10/25 06:00 CRDT- 2015/06/07 06:00 PHST- 2014/12/21 00:00 [received] PHST- 2015/04/23 00:00 [accepted] PHST- 2015/06/07 06:00 [entrez] PHST- 2015/06/07 06:00 [pubmed] PHST- 2016/10/25 06:00 [medline] AID - 10.1007/s00441-015-2207-7 [pii] AID - 10.1007/s00441-015-2207-7 [doi] PST - ppublish SO - Cell Tissue Res. 2016 Feb;363(2):497-511. doi: 10.1007/s00441-015-2207-7. Epub 2015 Jun 6.