Molecular mechanisms of microglial process extension and migration

• Project/Area Number: 21500363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: OHSAWA Keiko 独立行政法人国立精神・神経医療研究センター, 神経研究所・代謝研究部, 室長 (40392435)
• Co-Investigator(Renkei-kenkyūsha): SANAGI Tomomi 独立行政法人国立精神・神経医療研究センター, 神経研究所代謝研究部, 研究員 (00527012)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: ミクログリア / 突起伸長 / 細胞移動 / 細胞外ヌクレオチド / アデノシン / 神経科学 / 脳神経 / シグナル伝達 / 細胞運動 / アデノシン受容体 / グリア

Research Abstract

Microglia are the primary immune surveillance cells in the brain. Microglial process extension and migration toward injured sites in the brain is triggered by the stimulation of the purinergic receptor P2Y12 by extracellular ATP. In this study, we found that adenosine A3 receptor(A3R) co-operated with P2Y12 to promote microglial process extension and migration. A3R mRNA was clearly observed in microglia sorted from normal adult brains. From these results we concluded that adenosine signaling might play an important role in mediating the change in microglial motility from the resting state to the activated state after brain injury or disease.

Research Products

• [Journal Article] Adenosine A3 receptor is involved in ADP-induced microglial process extension and migration (2012)
  • Author(s): Ohsawa K, Sanagi T, Nakamura Y, Suzuki E, Inoue K, Kohsaka S.
  • Journal Title: J. Neurochem Volume: 121(2) Issue: 2 Pages: 217-227
  • DOI: 10.1111/j.1471-4159.2012.07693.x
  • Peer Reviewed
• [Journal Article] Involvement of activated microglia in increased vulnerability of motoneurons after facial nerve avulsion in presymptomatic amyotrophic lateral sclerosis model rats (2012)
  • Author(s): Sanagi T, Nakamura Y, Suzuki E, Uchino S, Aoki M, Warita H, Itoyama Y, Kohsaka S, Ohsawa K.
  • Journal Title: GLIA Volume: 60 Issue: 5 Pages: 782
  • DOI: 10.1002/glia.22308
  • Peer Reviewed
• [Journal Article] Dynamic motility of microglia : Purinergic modulation of microglial movement in the normal and pathological brain (2011)
  • Author(s): Ohsawa K, Kohsaka S.
  • Journal Title: GLIA Volume: 59(12) Issue: 12 Pages: 1793-1799
  • DOI: 10.1002/glia.21238
  • Peer Reviewed
• [Journal Article] Appearance of phagocytic microglia adjacent to motoneurons in spinal cord tissue from a presymptomatic transgenic rat model of amyotrophic lateral sclerosis (2010)
  • Author(s): Sanagi T, Yuasa S, Nakamura Y, Suzuki E, Aoki M, Warita H, Itoyama Y, Uchino S, Kohsaka S, Ohsawa K.
  • Journal Title: J Neurosci Res Volume: 88(12) Pages: 2736-2746
  • Peer Reviewed
• [Journal Article] P2Y12 receptor-mediated integrin-β1 activation regulates microglial process extension induced by ATP (2010)
  • Author(s): Ohsawa K, Irino Y, Sanagi T, Nakamura Y, Suzuki E, Inoue K, Kohsaka S.
  • Journal Title: Glia Volume: 58(7) Pages: 790-801
  • Peer Reviewed
• [Journal Article] Appearance of phagocytic microglia adjacent to motoneurons in spinal cord Tissue from a presymptomatic transgenic rat model of amyotrophic lateral sclerosis. (2010)
  • Author(s): Tomomi Sanagi
  • Journal Title: J.Neurosci.Res. Volume: 88 Pages: 2736-2746
  • Peer Reviewed
• [Journal Article] P2Y12 receptor-mediated integrin-β1 activation regulates microglial process extension induced by ATP (2010)
  • Author(s): Keiko Ohsawa
  • Journal Title: Glia 58 Pages: 790-801
  • Peer Reviewed
• [Presentation] Involvement of adenosine A3 receptor in microglial process extension (2011)
  • Author(s): 大澤圭子
  • Organizer: 第54回日本神経化学会大会第54回日本神経化学会大会第54回日本神経化学会大会第54回日本神経化学会大会
  • Place of Presentation: 石川県
  • Year and Date: 2011-09-27
• [Presentation] Involvement of adenosine A3 receptor in microglial process extension (2011)
  • Author(s): 大澤圭子
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 瑠璃光(石川県)
  • Year and Date: 2011-09-27
• [Presentation] アデノシンシグナルによるミクログリアの突起伸長調節 (2011)
  • Author(s): 大澤圭子
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 神奈川県、パシフィコ横浜
  • Year and Date: 2011-09-17
• [Presentation] アデノシンシグナルによるミクログリアの突起伸長調節 (2011)
  • Author(s): 大澤圭子
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-09-17
• [Presentation] アデノシンシグナルによるミクログリアの遊走と突起伸長調節 (2010)
  • Author(s): 大澤圭子
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 兵庫県神戸ポートアイランド
  • Year and Date: 2010-12-08
• [Presentation] Involvement ofβ1 integrin activation by P2Y12 receptor in microglial process extension (2010)
  • Author(s): Ohsawa K
  • Organizer: 第29回内藤コンファレンスGLIA WORLD
  • Place of Presentation: 神奈川県湘南交際村センター
  • Year and Date: 2010-10-06
• [Presentation] Involvement of β1 integrin activation by P2Y 12 receptor in microglial process extension (2010)
  • Author(s): 大澤圭子
  • Organizer: 第29回内藤コンファレンスGLIA WORLD
  • Place of Presentation: 神奈川県 湘南交際村センター
  • Year and Date: 2010-10-06
• [Presentation] 神経変性疾患におけるミクログリアの動態変化 (2010)
  • Author(s): 大澤圭子
  • Organizer: 第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会
  • Place of Presentation: 兵庫県神戸ポートアイランド
  • Year and Date: 2010-09-02
• [Presentation] Involvement ofβ1 integrin activation by P2Y12 receptor in microglial process extension (2009)
  • Author(s): Ohsawa K
  • Organizer: Involvement ofβ1 integrin activation by P2Y12 receptor in microglial process extension
  • Place of Presentation: 韓国釜山展示コンベンションセンター
  • Year and Date: 2009-08-25
• [Presentation] ATP受容体P2Y12を介したインテグリンβ1活性化によるミクログリア突起伸長調節 (2009)
  • Author(s): 大澤圭子
  • Organizer: ISN/APSN 2009
  • Place of Presentation: 釜山展示コンベンションセンター
  • Year and Date: 2009-08-25
• [Presentation] Integrinβ1 activation by P2Y12 receptor is involved in microglial process extension (2009)
  • Author(s): Ohsawa K
  • Organizer: Fukuoka Purine 2009
  • Place of Presentation: ザ福岡ザルイガンスホテル
  • Year and Date: 2009-07-24
• [Presentation] Integrin β1 activation by P2Y12 receptor is involved in microglial process extension (2009)
  • Author(s): 大澤圭子
  • Organizer: Fukuoka Purine 2009
  • Place of Presentation: ザルイガンスホテル
  • Year and Date: 2009-07-24
• [Presentation] ミクログリアの形態変化と遊走-細胞外ATPによる遊走と突起伸長の調節分子機構- (2009)
  • Author(s): 大澤圭子
  • Organizer: 第52回日本神経化学会大会
  • Place of Presentation: 群馬伊香保温泉ホテル天望
  • Year and Date: 2009-06-24
• [Presentation] ミクログリアの形態変化と遊走-細胞外ATPによる遊走と突起伸長の調節分子機構- (2009)
  • Author(s): 大澤圭子
  • Organizer: 第52回日本神経化学会大会
  • Place of Presentation: 伊香保温泉 ホテル天望
  • Year and Date: 2009-06-24