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Effects of uric acid transfer into the brain via the choroid plexus in dementia

Research Project

Project/Area Number 20K16550
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionKagawa University

Principal Investigator

Uemura Naoya  香川大学, 医学部, 助教 (20795124)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords尿酸 / 認知症 / 脈絡叢 / 抗酸化作用 / 神経保護作用 / 術後せん妄 / 認知機能障害 / 高尿酸血症
Outline of Research at the Start

尿酸は痛風や高尿酸血症の原因因子として知られ、心血管疾患との関連が注目されている。一方で、強力な抗酸化物質として神経保護作用を持つことが知られており、脳梗塞巣の縮小に尿酸投与が有用であったという報告がある。当研究室で尿酸の輸送体であるURAT1,GLUT9 が脈絡叢に存在する可能性をヒト剖検脳で新規に見出し報告した。尿酸が全身循環から脳内に血液脳関門を通過して移行しうると考えた。血清尿酸値の認知機能への影響を解明することでこの仮説を検証する。尿酸の認知機能への影響の解明が、難治性神経疾患への新たな予防法・治療法開発につながると期待される。

Outline of Final Research Achievements

Our laboratory conducted a retrospective observational study on 2,071 patients admitted to the intensive care unit (ICU) after high-invasive surgery, investigating the relationship between serum uric acid levels and postoperative delirium. After excluding patients with a history of central nervous system diseases, postoperative neurosurgery, multiple surgeries, emergency surgeries, and end-stage renal failure, statistical analysis was performed on 558 patients. Delirium evaluation was conducted using the CAM-ICU, a monitoring tool for delirium in ICU patients. There were 78 patients (approximately 14%) who were CAM-ICU (+). In univariate analyses using t-tests and Mann-Whitney U tests, there were significant differences in age, severity (ASA-PS, APACHE II score), and total intraoperative opioid dose, but propensity score analysis did not identify low serum uric acid levels as a risk factor for postoperative delirium.

Academic Significance and Societal Importance of the Research Achievements

近年、股関節骨折手術を受ける高齢患者において術前血清尿酸値の低下が術後せん妄の危険因子である可能性があると報告された(BMC Anesthesiol 2022 ; 22(1): 282)。また、血清尿酸/クレアチニン比が尿路結石を受ける高齢患者において術後せん妄の独立した危険因子であると報告され(Clin Interv Aging 2023 ; 18: 81-92)、血清尿酸値と術後せん妄の関係が注目されている。尿酸の認知機能への影響の解明することで患者の予後を改善し、認知症、せん妄や他の難治性神経疾患の新たな予防法・治療法開発につながるという創造性がある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2024 2023 2022 2021 2020

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Distribution of Monocarboxylate Transporters in Brain and Choroid Plexus Epithelium2023

    • Author(s)
      Ueno Masaki、Chiba Yoichi、Murakami Ryuta、Miyai Yumi、Matsumoto Koichi、Wakamatsu Keiji、Takebayashi Genta、Uemura Naoya、Yanase Ken
    • Journal Title

      Pharmaceutics

      Volume: 15 Issue: 8 Pages: 2062-2062

    • DOI

      10.3390/pharmaceutics15082062

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] E-Cadherin Is Expressed in Epithelial Cells of the Choroid Plexus in Human and Mouse Brains2023

    • Author(s)
      Takebayashi Genta、Chiba Yoichi、Wakamatsu Keiji、Murakami Ryuta、Miyai Yumi、Matsumoto Koichi、Uemura Naoya、Yanase Ken、Shirakami Gotaro、Ogino Yuichi、Ueno Masaki
    • Journal Title

      Current Issues in Molecular Biology

      Volume: 45 Issue: 10 Pages: 7813-7826

    • DOI

      10.3390/cimb45100492

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolites and Biomarker Compounds of Neurodegenerative Diseases in Cerebrospinal Fluid2022

    • Author(s)
      Wakamatsu Keiji、Chiba Yoichi、Murakami Ryuta、Miyai Yumi、Matsumoto Koichi、Kamada Masaki、Nonaka Wakako、Uemura Naoya、Yanase Ken、Ueno Masaki
    • Journal Title

      Metabolites

      Volume: 12 Issue: 4 Pages: 343-343

    • DOI

      10.3390/metabo12040343

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunoreactivity of receptor and transporters for lactate located in astrocytes and epithelial cells of choroid plexus of human brain2021

    • Author(s)
      Murakami Ryuta、Chiba Yoichi、Nishi Nozomu、Matsumoto Koichi、Wakamatsu Keiji、Yanase Ken、Uemura Naoya、Nonaka Wakako、Ueno Masaki
    • Journal Title

      Neuroscience Letters

      Volume: 741 Pages: 135479-135479

    • DOI

      10.1016/j.neulet.2020.135479

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical expression of osteopontin and collagens in choroid plexus of human brains2021

    • Author(s)
      Wakamatsu Keiji、Chiba Yoichi、Murakami Ryuta、Matsumoto Koichi、Miyai Yumi、Kawauchi Machi、Yanase Ken、Uemura Naoya、Ueno Masaki
    • Journal Title

      Neuropathology

      Volume: 42 Issue: 2 Pages: 117-125

    • DOI

      10.1111/neup.12791

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium2020

    • Author(s)
      Chiba Yoichi、Murakami Ryuta、Matsumoto Koichi、Wakamatsu Keiji、Nonaka Wakako、Uemura Naoya、Yanase Ken、Kamada Masaki、Ueno Masaki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 19 Pages: 7230-7230

    • DOI

      10.3390/ijms21197230

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒトおよびマウス脳の脈絡叢上皮細胞間におけるE-カドヘリンの局在について2024

    • Author(s)
      竹林玄太
    • Organizer
      第113回日本病理学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ヒト脳における尿酸輸送の実体と尿酸の術後せん妄への影響2021

    • Author(s)
      植村直哉 上野正樹
    • Organizer
      第54回日本痛風・尿酸核酸学会総会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-04-28   Modified: 2025-01-30  

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