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In vivo regulation of chondroitin sulfate gene to recovery from spinal cord injury

Research Project

Project/Area Number 26462232
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionAichi Medical University

Principal Investigator

Takeuchi Kosei  愛知医科大学, 医学部, 教授 (90206946)

Co-Investigator(Kenkyū-buntansha) 依田 浩子  新潟大学, 医歯学系, 准教授 (60293213)
鈴木 宏昌  愛知医科大学, 医学部, 准教授 (30340300)
Co-Investigator(Renkei-kenkyūsha) TAMADA Yasushi  信州大学, 繊維学部, 教授 (70370666)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords再生治療 / 神経再生 / バイオマテリアル / 遺伝子治療 / 再生医療 / 脊髄損傷 / コンドロイチン硫酸 / DDS / 遺伝子発現制御 / グリコサミノグリカン / 遺伝子抑制
Outline of Final Research Achievements

Injured adult neurons in the mammalian central nervous system (CNS) rarely regenerate, because some of the intracellular and cell-surface environmental factors inhibit axon regrowth. Chondroitin sulfate (CS) is the most abundant and potent exogenous inhibitor of axonal regeneration. CSGalNAcT1 is a key enzyme in CS biosynthesis. The sponge forms biomaterials impregnated with a mixture containing small molecule compounds or siRNAs was placed on the lesion area in mice suffered neural injuries. The recovery of these mice which treated with drug delivery systems reached the levels of satisfactory amelioration comparable to those of KO mice. Taken together, our results indicated that our drug and delivery system is a promising therapeutic target for treatment of the spinal cord injury and brain infarction, and many treatments of the neural damage.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (43 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 5 results) Presentation (31 results) (of which Int'l Joint Research: 3 results,  Invited: 10 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] EMBL/Heidelberg University(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Sanford Burrnham Medical Institute(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Extracellular Signals induce Glycoprotein M6a Clustering of Lipid-rafts and associated Signaling Molecules.2017

    • Author(s)
      Honda A, Ito Y, Takahashi-Niki, Matsushita N, Nozumi M, Tabata H, Takeuchi K, Igarashi M
    • Journal Title

      J Neurosci.

      Volume: 37(15) Issue: 15 Pages: 4046-4064

    • DOI

      10.1523/jneurosci.3319-16.2017

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex2017

    • Author(s)
      Hou X, Yoshioka N, Tsukano H, Sakai A, Miyata S, Watanabe Y, Yanagawa Y, Sakimura K, Kitagawa H, Hensch T, Takeuchi T, Igarashi M, and Sugiyama S
    • Journal Title

      Scientific rep.

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Claudin-21 has a paracellular channel role at tight junctions2016

    • Author(s)
      Claudin-21 Has a Paracellular Channel Role at Tight Junctions.
    • Journal Title

      Mol Cell Biol.

      Volume: 36 Issue: 6 Pages: 954

    • DOI

      10.1128/mcb.00758-15

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Amelioration of neuronal injury by the expression regulation of the glycosaminoglycan2015

    • Author(s)
      Takeuchi K.
    • Journal Title

      Seikagaku.

      Volume: 87(6) Pages: 744-748

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A newly identified mouse hypothalamic area having bidirectional neural connections with the lateral septum: the perifornical area of the anterior hypothalamus rich in chondroitin sulfate proteoglycans.2015

    • Author(s)
      Horii-Hayashi N, Sasagawa T, Hashimoto T, Kaneko T, Takeuchi K, Nishi M.
    • Journal Title

      Eur J Neurosci.

      Volume: 42(6) Issue: 6 Pages: 2322-2234

    • DOI

      10.1111/ejn.13024

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pioneering Axons Regulate Neuronal Polarization in the Developing Cerebral Cortex.2014

    • Author(s)
      Namba T, Kibe Y, Funahashi Y, Nakamuta S, Takano T, Ueno T, Shimada A, Kozawa S, Okamoto M, Shimoda Y, Oda K, Wada Y, Masuda T, Sakakibara A, Igarashi M, Miyata T, F-S Catherine, Takeuchi K, Kaibuchi K.
    • Journal Title

      Neuron

      Volume: 81(4) Issue: 4 Pages: 814-829

    • DOI

      10.1016/j.neuron.2013.12.015

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of T-cadherin in Axonal Pathway Formation in Neocortical Circuits2014

    • Author(s)
      Hayano Y., Zhao H., Kobayashi H., *Takeuchi K. and *Yamamoto N.
    • Journal Title

      Development

      Volume: 141 Issue: 24 Pages: 4784-4793

    • DOI

      10.1242/dev.108290

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 中枢神経・脊髄損傷後再生治療に向けての核酸医薬の可能性2017

    • Author(s)
      武内恒成
    • Organizer
      第2回革新的バイオ研究開発シンポジウム(日本核酸医薬学会)
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Year and Date
      2017-01-20
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 神経損傷後修復回復とその回路トレーシング2016

    • Author(s)
      武内恒成
    • Organizer
      第39回神経組織培養研究会
    • Place of Presentation
      横浜ランドマークタワー(横浜)
    • Year and Date
      2016-11-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 糖鎖発現制御による神経再生・脊髄損傷治療の可能性2016

    • Author(s)
      武内恒成、松下夏樹
    • Organizer
      第38回日本生物学的精神医学会・第59回日本神経化学会大会合同年会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2016-09-09
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Axonal regeneration after nerve injury induces phosphorylation of GAP-432016

    • Author(s)
      Masayasu Okada, Asami Kawasaki, Kosei Takeuchi, Michihiro Igarashi
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] New trials for the regulation of chondroitin sulfate expression by gene knockdown system to recovery from spinal cord injury2016

    • Author(s)
      K. Takeuchi
    • Organizer
      10th FENS Forum of Neuroscience
    • Place of Presentation
      コペンハーゲン(デンマーク)
    • Year and Date
      2016-07-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脊髄損傷再生における回路再編と、回路を診るウイルス発現系2016

    • Author(s)
      武内恒成、松下夏樹
    • Organizer
      第3回「適応回路シフト」領域会議(熱の班会議)・研究戦略ワークショップ
    • Place of Presentation
      ホテルリステル猪苗代(福島)
    • Year and Date
      2016-06-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] リン酸化プロテオミクスで同定された、神経成長関連分子群の責任キナーゼの解析2016

    • Author(s)
      河嵜麻実、小林大記、野住素広、玉田 篤、武内恒成、崎村健司、仁科博史、中津 史、
    • Organizer
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都テルサ(京都)
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Orally active siRNA targeting carbohydrate sulfotransferase 15 alleviates colonic mucosal injury in mice2016

    • Author(s)
      Hiroyuki Yoneyama, Kosei Takeuchi
    • Organizer
      DDW 2016 (Digestive Disease Week 2016)
    • Place of Presentation
      San Diego USA
    • Year and Date
      2016-05-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] コンドロイチン硫酸合成酵素遺伝子欠損マウスに生じる顎顔面発育異2016

    • Author(s)
      依田浩子、森田航、柴田俊一、和田芳野、五十嵐道広、武内恒成
    • Organizer
      第121回 日本解剖学会大会
    • Place of Presentation
      ビッグパレットふくしま(福島)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
  • [Presentation] リン酸化プロテオミクスで同定された、神経成長関連分子群の責任キナーゼの解析 一般口頭発表2015

    • Author(s)
      河嵜麻実、小林大記、岡田正康、野住素広、武内恒成、五十嵐道弘
    • Organizer
      第38回日本分子生物学会年会第88回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
  • [Presentation] リン酸化プロテオミクスで同定された、神経成長関連分子群の責任キナーゼの解析 ポスター発表2015

    • Author(s)
      河嵜麻実、小林大記、岡田正康、野住素広、武内恒成、五十嵐道弘
    • Organizer
      第38回日本分子生物学会年会第88回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] 糖鎖発現制御による中枢神経再生治療とその創薬スクリーニング培養系2015

    • Author(s)
      武内恒成、五十嵐道弘、松下夏樹
    • Organizer
      第37回神経組織培養研究会
    • Place of Presentation
      霧島国際ホテル(熊本)
    • Year and Date
      2015-11-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Knockdown of glycoprotein M6a in utero delayed the determination of neuronal polarity2015

    • Author(s)
      Yasuyuki Ito, Atsuko Honda, Kosei Takeuchi, Natsuki Matsushita, Michihiro Igarashi
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      大宮ソニックシティホール(埼玉)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Anti-phosho-GAP-43 pSer96 antibody as a novel molecular marker for axonal growth and regeneration2015

    • Author(s)
      Masayasu Okada, Asami Kawasaki, Kosei Takeuchi, Atsushi Tamada, Fubito Nakatsu, Yukihiko Fujii, Michihiro Igarashi
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      大宮ソニックシティホール(埼玉)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
  • [Presentation] JNK-mediated phosphorylation of GAP-43 promotes axonal growth2015

    • Author(s)
      Asami Kawasaki, Daiki Kobayashi, Masayasu Okada, Kosei Takeuchi, Michihiro Igarashi
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      大宮ソニックシティホール(埼玉)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Mice lacking in an enzyme involved in chondroitin sulfate synthesis shows better recovery from spinal cord injury.2015

    • Author(s)
      Kosei Takeuchi
    • Organizer
      25th International Society for Neurochemistry
    • Place of Presentation
      ケアンズコンベンションセンター オーストラリア ケアンズ
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 糖鎖発現制御による脊髄損傷・中枢神経再生治療の可能性 -バイオマテリアルと創薬展開 -2015

    • Author(s)
      武内恒成
    • Organizer
      新学術領域研究 ”プラズマ医療科学の創生“+”統合的神経機能の制御を標的とした糖鎖の作動原理解明“合同公開シンポジウム
    • Place of Presentation
      名古屋大学 野依記念学術交流館(愛知)
    • Year and Date
      2015-08-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] In vivo phosphorylation sites of GAP-43, involved axonal growth, is phosphorylated by JNK12015

    • Author(s)
      Daiki Kobayashi, Asami Kawasaki, Kosei Takeuchi, Michihiro Igarashi
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫)
    • Year and Date
      2015-07-29
    • Related Report
      2015 Research-status Report
  • [Presentation] 医学部初年次学生の剽窃に関する現状と意識2015

    • Author(s)
      宮本 淳、仙石昌也、山森孝彦、久留友紀子、橋本貴宏、武内恒成、小島貞夫
    • Organizer
      第47回日本医学教育学会大会
    • Place of Presentation
      朱鷺メッセ新潟コンベンションセンター(新潟)
    • Year and Date
      2015-07-24
    • Related Report
      2015 Research-status Report
  • [Presentation] 神経成長関連蛋白質GAP-43のJNK依存性リン酸化は軸索伸長を促進する2015

    • Author(s)
      河嵜麻実、小林大記、武内恒成、五十嵐道弘
    • Organizer
      第67回日本細胞生物学会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2015-07-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 細胞外基質グリコサミノグリカン制御および神経細胞接着分枝の人為発現制御による神経組織構築と再編成 ―中枢神経再生と神経極性発生解析―2015

    • Author(s)
      武内恒成、五十嵐道弘
    • Organizer
      第67回日本細胞生物学会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2015-06-30
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Linking genotype to phenotype in mice molars by means of morphometric mapping2015

    • Author(s)
      Wataru Morita, Naoki Morimoto, Hiroko Ida-Yonemochi, Kosei Takeuchi, Michihiro Igarashi, Hayato Ohshima
    • Organizer
      第120回日本解剖学会総会・全国学術集会、第92回日本生理学会大会 合同大会
    • Place of Presentation
      神戸国際会議場・展示場(兵庫)
    • Year and Date
      2015-03-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 糖転移合成酵素の発現制御による脊髄損傷治療2014

    • Author(s)
      武内恒成
    • Organizer
      平成26年度包括脳ネットワーク冬のシンポジウム 新学術領域研究「精神神経疾患研究の現状と展望:新学術5領域の相互理解・連携を目指して」
    • Place of Presentation
      東京医科歯科大 鈴木章夫記念講堂
    • Year and Date
      2014-12-11
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 神経成長関連蛋白質GAP-43のJNK依存性リン酸化は軸索伸長を促進する2014

    • Author(s)
      河嵜麻実、和田芳野、岡田正康、吉岡望、野住素広、武内恒成、五十嵐道弘
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川))
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Amelioration of spinal cord injury in the mice lacking in the enzymes of chondroitin sulfate2014

    • Author(s)
      K. Takeuchi
    • Organizer
      SFG & JSCR 2014 Joint Annual Meeting - Satellite II: Glycans in Neuroscience
    • Place of Presentation
      Honolulu, Hawaii
    • Year and Date
      2014-11-16 – 2014-11-19
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] In vivo RNAi against the enzymes synthesizing chondroitin sulfate induces the effective recovery from the spinal cord injury2014

    • Author(s)
      M. Igarashi, K. Takeuchi
    • Organizer
      Cell Symposia Translational Neuroscience
    • Place of Presentation
      Arlington. VA. USA
    • Year and Date
      2014-11-13 – 2014-11-14
    • Related Report
      2014 Research-status Report
  • [Presentation] コンドロイチン硫酸転移酵素CSGaINAcT1は脊髄損傷修復と神経発生に重要である2014

    • Author(s)
      武内恒成、五十嵐道弘
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-10-16
    • Related Report
      2014 Research-status Report
  • [Presentation] グリコサミノグリカン制御による神経再生・脊髄損傷修復と神経形成2014

    • Author(s)
      武内恒成、五十嵐道弘
    • Organizer
      第57回日本神経化学会大会・第36回日本生物学的精神医学会合同年会
    • Place of Presentation
      奈良県新公会堂(奈良)
    • Year and Date
      2014-09-29
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Abnormal glycan diversity of perineuronal nets in mice lacking in the chondroitin sulfate- synthesizing enzymes2014

    • Author(s)
      吉岡望、渡邊裕美、武内恒成、五十嵐道弘
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜 (神奈川)
    • Year and Date
      2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 細胞外環境コミュニケーションを介した形態形成とその維持  ー神経発生・細胞移動と極性決定へのアプローチー2014

    • Author(s)
      武内恒成、川内健史
    • Organizer
      第66回日本細胞生物学会
    • Place of Presentation
      奈良県新公会堂(奈良)
    • Year and Date
      2014-06-11
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] タイトジャンクション構成タンパク質クローディン21の解析2014

    • Author(s)
      柏原宏香、山本康子、峯田克彦、武内恒成、田中啓雄、山崎裕自、田村 淳、斉藤邦明、 月田早智子
    • Organizer
      第66回日本細胞生物学会
    • Place of Presentation
      奈良県新公会堂(奈良)
    • Year and Date
      2014-06-11
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] コンドロイチン硫酸生合成を阻害するアンチセンス核酸2017

    • Inventor(s)
      武内恒成
    • Industrial Property Rights Holder
      武内恒成
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-072315
    • Filing Date
      2017-03-31
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] Anti Gap43 Antibody2016

    • Inventor(s)
      武内恒成
    • Industrial Property Rights Holder
      武内恒成
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-01-15
    • Acquisition Date
      2017-01-10
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 抗GAP43抗体2015

    • Inventor(s)
      武内恒成
    • Industrial Property Rights Holder
      武内恒成
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-10-19
    • Acquisition Date
      2016-04-25
    • Related Report
      2015 Research-status Report
    • Overseas

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Published: 2014-04-04   Modified: 2022-02-16  

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