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グリア・ニュ ロン相互作用による神経機能維持メカニズムとその加齢変化の解析

Research Project

Project/Area Number15082205
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOsaka City University

Principal Investigator

木山 博資  Osaka City University, 大学院・医学研究科, 教授 (00192021)

Co-Investigator(Kenkyū-buntansha) 中込 咲綾  大阪市立大学, 大学院・医学研究科, 助教 (60423894)
小西 博之  大阪市立大学, 大学院・医学研究科, 助教 (90448746)
前田 光代  大阪市立大学, 大学院医学研究科, 講師 (40122080)
瀬尾 寿美子 (桐生 寿美子)  大阪市立大学, 大学院医学研究科, 講師 (70311529)
濤川 一彦  旭川医科大学, 医学部, 助教授 (50312468)
Project Period (FY) 2003 – 2007
Project Status Completed(Fiscal Year 2007)
Budget Amount *help
¥64,000,000 (Direct Cost : ¥64,000,000)
Fiscal Year 2007 : ¥12,800,000 (Direct Cost : ¥12,800,000)
Fiscal Year 2006 : ¥12,800,000 (Direct Cost : ¥12,800,000)
Fiscal Year 2005 : ¥12,800,000 (Direct Cost : ¥12,800,000)
Fiscal Year 2004 : ¥12,800,000 (Direct Cost : ¥12,800,000)
Fiscal Year 2003 : ¥12,800,000 (Direct Cost : ¥12,800,000)
Keywordsマウス / 運動ニューロン / 舌下神経 / 脳・神経 / ミクログリア / CCR5 / 神経損傷 / マクロファージ / シュワン細胞 / サイトカイン / アネキシン / ラッフリング / PAP / Reg / 神経再生 / Regファミリー / シュワン増殖 / 末梢神経
Research Abstract

グリア・ニューロン相互作用の変化を解析するために,各種神経損傷モデルを用いて,神経・グリア相互作用に関係するミクログリアの作用と各種分子の同定を行った。本年度は(1)ミクログリアの応答と神経細胞死の関連,(2)ミクログリアに発現するGPCRの神経機能維持に関する解析,を中心に行った。(1)マウス運動神経は軸索損傷により半数以上が緩やかな細胞死をする。この時のミクログリアの動態を電子顕微鏡で観察した所,ミクログリアの接着のない運動ニューロンが存在し,それらは細胞死に至ることが新たに明らかになった。このことは,軸索損傷後ミクログリアは運動ニューロンを取り囲み生存のための環境を作りだしている可能性を示唆していると考えられた。(2)約300の蛋白共役型受容体のプライマーと,神経損傷側と健常側の神経核から抽出したRNAを用い,神経再生過程で発現が上昇するGPCRのスクリーニングを行った。この結果得られた遺伝子のうち,CCR5に注目してCCR5のリガンドであるRantesの発現動態を解析した。この結果受容体はミクログリアにリガンドは損傷運動ニューロンで発現していることが明らかになった。また,CCR5ノックアウトマウスでは運動ニューロンの細胞死が加速した。このことから,軸索損傷後にミクログリアで発現するCCR5は損傷運動ニューロンとリガンドを介して運動ニューロンの生存にポジティブに作用していることが推測された。10年ほど前から使用していたPCR用のPCR Thermal Cyclerとデータ取り込みのための顕微鏡デジタルカメラがいずれも老朽化のため何れも本研究中に修理不能となり,研究の取りまとめに多大な影響をきたしたので,当初予定していなかったが,主な物品として急遽購入した。

Report

(5results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report

Research Products

(28results)

All 2008 2007 2006 2005 2004 Other

All Journal Article Presentation Publications

  • [Journal Article] Alteration of glial cell line-derived neurotrophic factor family receptor alpha-2 m RNA expression and its co-expression with neuronal nitric oxide synthase in pelvic ganglia following unilateral cavernous nerve injury2008

    • Author(s)
      Hisasue S, Kato R, Kobayashi K, Suetomi T, Kiyama H, Tsukamoto T
    • Journal Title

      Int J Urol 15(1)

      Pages : 82-86

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suture of transected nerve suppresses expression of BH3-only protein Noxa in nerve-transected motor neurons of C57BL/6J mouse,2007

    • Author(s)
      Gamo K, Kiryu-Seo S, Yoshikawa H, Kiyama H
    • Journal Title

      J Neurotrauma 24(5)

      Pages : 876-884

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Melanocortin receptor 4 is induced in nerve-injured motor and sensory neurons of mouse2007

    • Author(s)
      Tanabe K, Gamo K, Aoki S, Wada K, iyama H
    • Journal Title

      J Neurochem 101(4)

      Pages : 1145-1152

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of peripherin as a novel Akt substrate in neurons2007

    • Author(s)
      Konishi H, Namikawa K, Shikata K, Kobatake Y, Tachibana T, Kiyama H
    • Journal Title

      J Biol Chem 282(32)

      Pages : 23491-23499

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pael Receptor Induces Death of Dopaminergic Neurons in the Substantia Nigra via Endoplasmic Reticulum Stress and Dopamine Toxicity,which is Enhanced under Condition of Parkin Inactivation.2007

    • Author(s)
      Kitao Y, Imai Y, Ozawa K, Kataoka A, Ikeda T, Soda M, Namikawa K, Kiyama H, Stern DM, Hori O, Wakamatsu K, Ito S, Itohara S, Takahashi R, Ogawa S
    • Journal Title

      Hum Mol Genet 16(1)

      Pages : 50-60

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pancreatitis-associated protein-III (PAP-III) is a novel macrophage chemoattractant implicated in nerve regeneration2006

    • Author(s)
      Namikawa K, Okamoto T, Suzuki A, Konishi H, Kiyama H
    • Journal Title

      J Neurosci 26(28)

      Pages : 7460-7467

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Unique anti-apoptotic activity of EAAC1 in injured motor neurons2006

    • Author(s)
      Kiryu-Seo S, Gamo K, Tachibana T, Tanaka K, Kiyama H
    • Journal Title

      EMBO J 25(14)

      Pages : 3411-3421

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A newly modified SCG10 promoter and Cre/loxP-mediated gene amplification system achieve highly specific neuronal expression in animal brains2006

    • Author(s)
      Namikawa K, Murakami K, Okamoto T, Okado H, Kiyama H
    • Journal Title

      Gene Therapy 13(16)

      Pages : 1244-1250

    • Related Report
      2006 Annual Research Report
  • [Journal Article] GTP Hydrolysis by the Rho Family GTPase TC10 Promotes Exocytic Vesicle Fusion.2006

    • Author(s)
      Kawase K, Nakamura T, Takaya A, Aoki K, Namikawa K, Kiyama H, Inagaki S, Takemoto H, Saltiel AR, Matsuda M
    • Journal Title

      Dev Cell 11(3)

      Pages : 411-421

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Targeted gene therapy toward astrocytoma using a Cre/loxP-based adenovirus system2006

    • Author(s)
      Maeda M, Namikawa K, Kobayashi I, Ohba N, Takahara Y, Kadono C, Tanaka A, Kiyama H
    • Journal Title

      Brain Res 1081

      Pages : 34-43

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Related Articles, Links Identification and functional characterization of mouse TPO1 as a myelin membrane protein.2006

    • Author(s)
      Fukazawa N, Ayukawa K, Nishikawa K, Ohashi H, Ichihara N, Hikawa Y, Abe T, Kudo Y, Kiyama H, Wada K, Aoki S
    • Journal Title

      Brain Res 1070(1)

      Pages : 1-14

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Annexin III implicated in the microglial response to motor nerve injury.2006

    • Author(s)
      Konishi H, Namikawa K, Kiyama H
    • Journal Title

      Glia in press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Induced expression of Rab24 GTPase and LC3 in nerve-injured motor neurons.2005

    • Author(s)
      Egami Y, Kiryu-Seo S, Yoshimura T, Kiyama H
    • Journal Title

      Biochem Biophys Res Commun 337

      Pages : 1206-1213

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Age related alteration of neurturin receptor GFRa2 and nNOS in pelvic ganglia.2005

    • Author(s)
      Hisasue S, Kato R, Suetomi T, Kato K, Suzuki K, Kobayashi K, Itoh N, Kiyama H, Tsukamoto T
    • Journal Title

      Neurobiol Aging in press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of Reg/PAP family members during motor nerve regeneration in rat.2005

    • Author(s)
      Namikawa K, Fukushima M, Murakami K, Suzuki A, Takasawa S, Okamoto H, Kiyama H
    • Journal Title

      Biochem Biophys Res Commun 332

      Pages : 126-134

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The p53-independent nuclear translocation of Cyclin G1 in degenerating neurons by ischemic and traumatic insults.2005

    • Author(s)
      Maeda M, Ampo K, Kiryu-Seo S, Konishi H, Ohba N, Kadono C, Kiyama H
    • Journal Title

      Exp Neurol 193(2)

      Pages : 350-360

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Noxa is a critical mediator of p53-dependent motor neuron death after nerve injury in adult mouse2005

    • Author(s)
      Kiryu-Seo S, Hirayama T, Kato R, Kiyama H
    • Journal Title

      J Neurosci 25(6)

      Pages : 1442-1447

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 神経損傷時のグリア・ニューロン間インターラクションとその破綻2005

    • Author(s)
      木山博資, 前田光代
    • Journal Title

      Clinical Neuroscience 23(2)

      Pages : 187-190

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Noxa is a critical mediator of p53-dependent motor neuron death after nerve injury in adult mouse.2005

    • Author(s)
      Kiryu-Seo S, Hirayama T, Kato R, Kiyama H.
    • Journal Title

      J Neurosci. 25(6)

      Pages : 1442-7

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Differential regulation of the regulatory subunits for phosphatidylinositol 3-kinase in response to motor nerve injury.2004

    • Author(s)
      Okamoto T, Namikawa K, Asano T, Takaoka K, Kiyama H.
    • Journal Title

      Mol Brain Res. 131(1-2)

      Pages : 119-25

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of damage-induced neuronal endopeptidase (DINE) mRNA in peri-infarct cortical and thalamic neurons following middle cerebral artery occlusion.2004

    • Author(s)
      Ohba N, Kiryu-Seo S, Maeda M, Muraoka M, Ishii M, Kiyama H.
    • Journal Title

      J Neurochem. 91(4)

      Pages : 956-64

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Critical role for DP5/Harakiri, a Bcl-2 homology domain 3-only Bcl-2 family member, in axotomy-induced neuronal cell death.2004

    • Author(s)
      Imaizumi K, Benito A, Kiryu-Seo S, Gonzalez V, Inohara N, Lieberman AP, Kiyama H, Nunez G.
    • Journal Title

      J Neurosci. 24(15)

      Pages : 3721-5

    • Related Report
      2004 Annual Research Report
  • [Presentation] Glia-Neuron interaction in neuronal regeneration and degeneration2007

    • Author(s)
      Kiyama H
    • Organizer
      The APSN symposium "Glial activation and Function"
    • Place of Presentation
      Dalian Medical University, Dalian, Rep. China
    • Related Report
      2007 Annual Research Report
  • [Presentation] 損傷神経細胞とミクログリアの微妙な関係-Kiss of microglia-Is it sweet or bitter?2007

    • Author(s)
      木山 博資
    • Organizer
      第50回日本神経化学会・第30回神経科学会合同大会、シンポジウム「脳神経回路機能障害におけるミクログリアの多面性」
    • Place of Presentation
      パシフィコ横浜、横浜
    • Related Report
      2007 Annual Research Report
  • [Publications] Maeda M, Kiyama H他: "Vesicular acetylcholine transporter can be a morphological marker for the reinnervation to muscle of regenerating motor axons"Neurosci Res. 48. 305-314 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuzaki H, Kiyama H他: "Brain Derived Neurotrophic Factor Rescues Neuronal Death Induced by Methamphetamine"Biol Psychiat. 59. 52-60 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki Y, Kiyama H他: "Collapsin Response Mediator Protein-2 accelerates axon regeneration of nerve-injured motor neurons of rat"J Neurochem. 86. 1042-1050 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakagomi A, Kiyama H他: "Expression of the Activating transcription factor 3 prevents c-Jun N-terminal kinase-induced neuronal death by promoting hear shock protein 27 expression and Akt activation"J Neurosci. 23. 5187-5196 (2003)

    • Related Report
      2003 Annual Research Report

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Published : 2003-04-01   Modified : 2018-03-28  

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