Pathogenesis and treatment of cognitive dysfunction induced by reduced clearance of cerebrospinal fluid associated with aging

• Project/Area Number: 23592142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Juntendo University
• Principal Investigator: MIYAJIMA Masakazu 順天堂大学, 医学部, 准教授 (60200177)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 老化 / 髄液 / 認知機能障害 / 水頭症 / クリアランス / LRG1 / 髄液のクリアランス / グリア細胞 / 神経細胞変性 / トランスジェニックマウス / 水チャンネル / neurodegeneration / transgenic mouse / 特発性正常圧水頭症 / アストロサイト / 神経細胞

Research Abstract

The function of LRG in the brain during aging and neurodegenerative diseases has not been investigated. Here, we observed hLRG expression in post-mortem human cerebral cortex. We then generated transgenic mice that over-expressed mouse LRG in the brain to examine the effects of mLRG accumulation. Our results show that in both humans and mouse brains, LRG increases with age. Increased LRG in neurons and glial cells was associated with mouse cerebral cortex neurodegeneration.

Research Products

• [Journal Article] Leucine-richα2-glycoprotein is a novel biomarker of neurodegenerative disease in human cerebrospinal fluid and causes neurodegeneration in mouse cerebral cortex (2013)
  • Author(s): Miyajima M, Nakajima M, Motoi Y, Moriya M, Sugano H, Ogino I, Nakamura E, Tada N, Kunichika M, Arai H
  • Journal Title: PLoS One Volume: 18,8(9)
• [Journal Article] Leucine-rich α2-glycoprotein is a novel biomarker of neurodegenerative disease in human cerebrospinal fluid and causes neurodegeneration in mouse cerebral cortex. (2013)
  • Author(s): Miyajima M, Nakajima M, Motoi Y, Moriya M, Sugano H, Ogino I, Nakamura E, Tada N, Kunichika M, Arai H
  • Journal Title: PLoS One Volume: 8
  • Peer Reviewed
• [Journal Article] Soluble amyloid precursor protein α in the cerebrospinal fluid as a diagnostic and prognostic biomarker for idiopathic normal pressure hydrocephalus. (2013)
  • Author(s): Miyajima M, Nakajima M, Ogino I, Miyata H, Motoi Y, Arai H
  • Journal Title: Eur J Neurol Volume: 20 Issue: 2 Pages: 236-242
  • DOI: 10.1111/j.1468-1331.2012.03781.x
  • Peer Reviewed
• [Journal Article] Brain localization of leucine-richα2-glycoprotein and its role (2012)
  • Author(s): Nakajima M, Miyajima M, Ogino I, Watanabe M, Hagiwara Y, Segawa T, Kobayashi K, Arai H
  • Journal Title: Acta Neurochir Suppl Volume: 113 Pages: 97-101
• [Journal Article] Brain localization of leucine-rich α2-glycoprotein and its role. (2012)
  • Author(s): Nakajima M, Miyajima M, et.al
  • Journal Title: Acta Neurochir Suppl Volume: 113 Pages: 97-101
  • Peer Reviewed
• [Journal Article] Leucine-rich α-2-glycoprotein is a marker for idiopathic normal pressure hydrocephalus. (2011)
  • Author(s): Nakajima M, Miyajima M, et.al
  • Journal Title: Acta Neurochir (Wien) Volume: 153(6) Pages: 1339-1346
  • Peer Reviewed
• [Presentation] Leucine-richα2-glycoprotein (LRG) is a novel biomarker of neurogenerative disease in human cerebrospinal fluid and causes neurodegeneration in mouse cerebral cortex (2013)
  • Author(s): Miyajima M
  • Organizer: Hydrocephalus
  • Place of Presentation: Athens
• [Presentation] Leucine-rich α2-glycoprotein (LRG) is a novel biomarker of neurogenerative disease in human cerebrospinal fluid and causes neurodegeneration in mouse cerebral cortex. (2013)
  • Author(s): Miyajima M
  • Organizer: Hydrocephalus 2013
  • Place of Presentation: Athens
• [Presentation] The evaluation of CSF biomarkers for idiopathic normal pressure hydrocephalus (iNPH) (2011)
  • Author(s): 宮嶋 雅一
  • Organizer: Hydrocephalus 2011
  • Place of Presentation: コペンハーゲン
• [Presentation] Leucine-rich alpha-2-glycoprotein conditioning マウスの解析
  • Author(s): 宮嶋 雅一
  • Organizer: 2012年日本水頭症脳脊髄液学会
  • Place of Presentation: 東京
• [Presentation] Guideline for management of iNPH and results of Japan shunt registry
  • Author(s): 宮嶋 雅一
  • Organizer: 第19回韓国機能脳神経外科学会
  • Place of Presentation: 韓国
  • Invited