title: Immunohistochemical and in situ hybridization study of urate transporters GLUT9/URATv1, ABCG2, and URAT1 in the murine brain.
abstract: BACKGROUND
  Uric acid (UA) is known to exert neuroprotective effects in the brain. However, the mechanism of UA regulation in the brain is not well characterized. In our previous study, we described that the mouse urate transporter URAT1 is localized to the cilia and apical surface of ventricular ependymal cells. To further strengthen the hypothesis that UA is transported transcellularly at the ependymal cells, we aimed to assess the distribution of other UA transporters in the murine brain.
  
  
  METHODS
  Immunostaining and highly-sensitive in situ hybridization was used to assess the distribution of UA transporters: GLUT9/URATv1, ABCG2, and URAT1.
  
  
  RESULTS
  Immunostaining for GLUT9 was observed in ependymal cells, neurons, and brain capillaries. Immunostaining for ABCG2 was observed in the choroid plexus epithelium and brain capillaries, but not in ependymal cells. These results were validated by in situ hybridization.
  
  
  CONCLUSIONS
  We propose that given their specific expression patterns in ependymal, choroid plexus epithelial, and brain capillary endothelial cells in this study, UA may be transported by these UA transporters in the murine brain. This may provide a novel strategy for targeted neuroprotection.
authors.affiliation: Department of Human Physiology and Pathology, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. nhtomioka@pharm.teikyo-u.ac.jp.
authors.forename: Naoko H
authors.identifier: http://orcid.org/0000-0002-0524-3410
authors.initials: NH
authors.lastname: Tomioka
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
authors.forename: Yoshifuru
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Department of Human Physiology and Pathology, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. hosoyamd@pharm.teikyo-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosoyamada
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics / Q000378:metabolism*; D019342:Acetic Acid; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002725:Chloroform; D004805:Ependyma / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D000432:Methanol; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027361:Organic Anion Transporters / Q000378:metabolism*; D012333:RNA, Messenger; D016707:Tissue Fixation
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; C501412:Abcg2 protein, mouse; D051246:Glucose Transport Proteins, Facilitative; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C109687:Slc22a12 protein, mouse; C498775:Slc2a9 protein, mouse; C046544:methacarn; D002725:Chloroform; D019342:Acetic Acid; D000432:Methanol