Regulation of the chondroitin sulfate and recovery systems from the spinal cord injury.

• Project/Area Number: 23592161
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Niigata University
• Principal Investigator: TAKEUCHI Kosei 新潟大学, 医歯(薬)学総合研究科, 客員研究員 (90206946)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 脊髄損傷 / 再生医療 / グリコサミノグリカン / 神経再生 / バイオマテリアル / 核酸医薬 / 神経発生 / 神経科学

Research Abstract

Extracellular factors that inhibit axon growth and intrinsic factors that promote it affect neural regeneration. Therapies targeting any single gene have not yet simultaneously optimized both types of factors. Chondroitin sulphate (CS), a glycosaminoglycan, is the most abundant extracellular inhibitor of axon growth. Here we show that mice carrying a gene knockout for CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, recover morecompletely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice.Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectorsof axon regeneration

Research Products

• [Journal Article] Pioneering Axons Regulate Neuronal Polarization in the Developing Cerebral Cortex (2014)
  • Author(s): Takashi Namba,Yuji Kibe, Yasuhiro Funahashi, Shinichi Nakamuta, Tetsuya Takano, Takuji Ueno, Akiko Shimada, Sachi Kozawa, Mayumi Okamoto,Yasushi Shimoda,Kanako Oda,Yoshino Wada,Tomoyuki Masuda, Akira Sakakibara,Michihiro Igarashi,Takaki Miyata,Catherine Faivre-Sarrailh, Kosei Takeuchi, Kozo Kaibuchi
  • Journal Title: Neuron Volume: 81 Pages: 814-829
  • Peer Reviewed
• [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
  • Peer Reviewed / Open Access
• [Journal Article] Chondroitin sulphate N-acetyl galactosaminyl-transferase-1 inhibits recovery from neural injury (2013)
  • Author(s): Kosei Takeuchi, Nozomu Yoshioka, Susumu Higa-Onaga, Yumi Watanabe, Shinji Miyata, Yoshino Wada, Chika Kudo, Masayasu Okada, Kentaro Ohko, Kanako Oda, Toshiya Sato, Minesuke Yokoyama, Natsuki Matsushita, Masaya Nakamura, Hideyuki Okano, Kenji Sakimura,Hitoshi Kawano, Hiroshi Kitagawa, Michihiro Igarashi
  • Journal Title: Nature Communications Volume: 4 Pages: 2740-2740
  • Peer Reviewed
• [Journal Article] Point Mutation in Syntaxin-1A Causes Abnormal Vesicle Recycling, Behaviors, and Short Term Plasticity (2013)
  • Author(s): Yumi Watanabe, Norikazu Katayama, Kosei Takeuchi, Tetsuya Togano, Rieko Itoh, Michiko Sato, Maya Yamazaki, Manabu Abe, Toshiya Sato, Kanako Oda, Minesuke Yokoyama, Keizo Takao, Masahiro Fukaya, Tsuyoshi Miyakawa, Masahiko Watanabe, Kenji Sakimura, Toshiya Manabe, Michihiro Igarashi
  • Journal Title: The Journal of Biological Chemistry Volume: 288(48) Pages: 34906-34919
  • Peer Reviewed
• [Journal Article] TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding (2013)
  • Author(s): Mayumi Okamoto, Takashi Namba, Tomoyasu Shinoda, Takefumi Kondo, Tadashi Watanabe, Yasuhiro Inoue, Kosei Takeuchi, Yukiko Enomoto, Kumiko Ota, Kanako Oda, Yoshino Wada, Ken Sagou, Kanako Saito, Akira Sakakibara, Ayano Kawaguchi, Kazunori Nakajima, Taiji Adachi, Toshihiko Fujimori, Masahiro Ueda, Shigeo Hayashi, Kozo Kaibuchi, Takaki Miyata
  • Journal Title: Nature Neuroscience Volume: 16(11) Pages: 1556-1566
  • Peer Reviewed
• [Journal Article] N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury. (2013)
  • Author(s): Kosei Takeuchi, Nozomu Yoshioka, Susumu Higa Onaga, Yumi Watanabe, et. al.
  • Journal Title: Nature Communications Volume: 4 Issue: 1 Pages: 2740-2740
  • DOI: 10.1038/ncomms3740
  • Peer Reviewed
• [Journal Article] Point Mutation in Syntaxin-1A Causes Abnormal Vesicle Recycling, Behaviors, and Short-term Plasticity. (2013)
  • Author(s): Yumi Watanabe, Norikazu Kata yama, Kosei Takeuchi, et. al.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 48 Pages: 34906-34919
  • DOI: 10.1074/jbc.m113.504050
  • Peer Reviewed / Open Access
• [Journal Article] Development of the dorsal ramus of the spinal nerve in the chick embryo : A close relationship between development and expression of guidance cues (2012)
  • Author(s): Masuda T., Sakuma C., Taniguchi M., Kanemoto A., Yoshizawa M., Satomi K., Tanaka H., Takeuchi K., Yaginuma H., Shiga T
  • Journal Title: Brain Research Volume: 1480 Pages: 30-40
  • Peer Reviewed
• [Journal Article] Development of the dorsal ramus of the spinal nerve in the chick embryo: A close relationship between development and expression of guidance cues. (2012)
  • Author(s): Masuda T., Sakuma C., Taniguchi M., Kanemoto A., Yoshizawa M., Satomi K., Tanaka H., Takeuchi K., Yaginuma H., Shiga T.
  • Journal Title: Brain Res. Volume: 1480 Pages: 30-40
  • DOI: 10.1016/j.brainres.2012.08.055
  • Peer Reviewed
• [Presentation] 神経極性決定に関与する4回膜貫通glycoprotein M6aの機能解析 (2013)
  • Author(s): 武内恒成、本多敦子、伊藤泰行、峯田克彦、五十嵐道弘
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際展示場(兵庫)
  • Year and Date: 2013-12-03
• [Presentation] CSGalNAcT1, an Enzyme Required for Chondroitin Sulfate Synthesis (2013)
  • Author(s): 武内恒成、吉岡望、岡田正康、五十嵐道弘
  • Organizer: is Critical to Recovery from Neural Injury「Neuroscience2013
  • Place of Presentation: San Diego Convention Center(サンディエゴ・アメリカ)
  • Year and Date: 2013-11-10
• [Presentation] New trial of gene knockdown system by the siRNA-absorbent silk sponge to recovery from spinal cord injury (2013)
  • Author(s): 武内恒成
  • Organizer: AMWC(Advanced Materials World Congress 2013
  • Place of Presentation: イズミル・トルコ
  • Year and Date: 2013-09-18
• [Presentation] コンドロイチン硫酸合成酵素欠損マウスにおける神経発生・発達異常 (2013)
  • Author(s): 吉岡望、比嘉進、武内恒成、五十嵐道弘
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2013-09-12
• [Presentation] Abnormal brain development/maturation in mice lacking in chondroitin sulfate - synthesizing enzymes (2013)
  • Author(s): 武内恒成
  • Organizer: ECMNET(European cooeration in science and technology)
  • Place of Presentation: オパレニカ・ポーランド
  • Year and Date: 2013-09-11
• [Presentation] 長円錐における網羅的なリン酸化タンパク質の探索 (2013)
  • Author(s): 河嵜麻実、武内恒成、野住素広、五十嵐道弘成
  • Organizer: Neuro2013 (第36回日本神経科学大会、第56回日本神経化学会大会、第23回日本神経回路学会大会)
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2013-06-22
• [Presentation] コンドロイチン硫酸合成酵素欠損マウスにおける神経発生・発達異常 (2013)
  • Author(s): 吉岡望、武内恒成、岡田正康、和田芳野、川野仁、五十嵐道弘
  • Organizer: Neuro2013 (第36回日本神経科学大会、第56回日本神経化学会大会、第23回日本神経回路学会大会)
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2013-06-22
• [Presentation] 神経成長円錐マーカー分子GAP43新規リン酸化ドメインとその認識抗体の応用 (2013)
  • Author(s): 河嵜麻実、野住素広、武内恒成、五十嵐道弘
  • Organizer: 第35回神経組織培養研究会
  • Place of Presentation: ホテル阪急エキスポパーク(大阪)
  • Year and Date: 2013-06-03
• [Presentation] Brain development/ maturation in mice lacking in chondroitin sulfate synthesizing enzymes (2013)
  • Author(s): 吉岡望、武内恒成、五十嵐道弘
  • Organizer: 25th国際神経化学学会(ISN)/米国神経化学学会(ASN) (ISN2013 Glial Satellite)
  • Place of Presentation: Hotel El Castellano(カンクン・メキシコ)
  • Year and Date: 2013-04-19
• [Presentation] グリコサミノグリカン発現制御による神経再生・発生 (2013)
  • Author(s): 武内恒成、吉岡望、比嘉進、川野仁、五十嵐道弘
  • Organizer: 第118回日本解剖学会総会
  • Place of Presentation: サンポートホール高松・香川国際会議場
• [Presentation] CSGalNAcT1, an Enzyme Required for Chondroitin Sulfate Synthesis, is Critical to Recovery from Neural Injury (2013)
  • Author(s): 武内恒成
  • Organizer: FENS meeting
  • Place of Presentation: プラハ（チェコ）
• [Presentation] Abnormal brain development/maturation in mice lacking in chondroitin sulfate - synthesizing enzymes (2013)
  • Author(s): 武内恒成
  • Organizer: ECMNET(European cooeration in science and technology)
  • Place of Presentation: オパレニカ（ポーランド）
  • Invited
• [Presentation] New trial of gene knockdown system by the siRNA-absorbent silk sponge to recovery from spinal cord injury (2013)
  • Author(s): 武内恒成
  • Organizer: AMWC(Advanced Materials World Congress 2013)
  • Place of Presentation: イズミル（トルコ）
• [Presentation] CSGalNAcT1, an Enzyme Required for Chondroitin Sulfate Synthesis, is Critical to Recovery from Neural Injury (2013)
  • Author(s): 武内恒成
  • Organizer: Neuroscience2013
  • Place of Presentation: 神戸
• [Presentation] 神経極性決定に関与する4回膜貫通glycoprotein M6aの機能解析 (2013)
  • Author(s): 武内恒成
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] グリコサミノグリカン発現制御による神経再生・発生 (2013)
  • Author(s): 武内恒成
  • Organizer: 第118回日本解剖学会総会
  • Place of Presentation: 香川
  • Invited
• [Presentation] コンドロイチン硫酸はマウス視覚野においてOtx2取り込みと臨界期可塑性を制御する (2012)
  • Author(s): 候旭濱、武内恒成、五十嵐道弘、杉山清佳
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-09-18
• [Presentation] Brain development abnormality and axon regeneration in the mice lacking in the enzymes synthesizing chondroitin sulfate (2012)
  • Author(s): 武内恒成.
  • Organizer: 第45回日本発生生物学会・第64回日本細胞生物学会合同大会
  • Place of Presentation: 神戸国際センター
• [Presentation] コンドロイチン硫酸の発現制御による神経再生機構 (2012)
  • Author(s): 武内恒成、吉岡望、渡部裕美、川嵜麻実、和田芳野、五十嵐道弘
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
• [Presentation] 損傷脳におけるコンドロイチン硫酸プロテオグリカンの産生メカニズム (2012)
  • Author(s): 吉岡望、武内恒成、阿相皓晃、黒田純子、五十嵐道弘、川野仁
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Cre/loxP組換え依存の標的遺伝子ノックダウン誘導のためのレンチウイルスベクターシステム (2012)
  • Author(s): 松下夏樹、松下佐知、武内恒成、八十島安伸、東山繁樹
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Axon regeneration in the mice lacking in the enzymes synthesizing chondroitin sulfate (2012)
  • Author(s): 武内恒成、吉岡望、川野仁、五十嵐道弘
  • Organizer: 8^<th> Forum of neuroscience
  • Place of Presentation: Barcelona, Spain
• [Presentation] Brain development abnormality and axon regeneration in the mice lacking in the enzymes synthesizing chondroitin sulfate (2012)
  • Author(s): 武内恒成
  • Organizer: 2^<nd> Annual Conference of COST Action ECMNet"Brain extracellular matrix in health and disease
  • Place of Presentation: Barcelona, Spain
• [Presentation] プロテオグリカン合成系の調節による神経損傷修復機構 (2012)
  • Author(s): 武内恒成、吉岡望、比嘉進、渡邊裕美、五十嵐道弘、川野仁
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] イムノグロブリン様細胞接着分子による生体内での軸索形成制御 (2012)
  • Author(s): 木部祐士、難波隆志、舟橋靖広、中牟田信一、武内恒成、貝淵弘三
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Axon regeneration in the mice lacking in the enzymes synthesizing chondroitin sulfate. (2012)
  • Author(s): Kosei Takeuchi, Yoshioka Nozomu, Susumu Higa, Hitoshi Kawano, Michihiro Igarashi
  • Organizer: 8th Forum of European Neurosciences (FENS meetings 2012)
  • Place of Presentation: Barcelona, Spain
• [Presentation] Brain development abnormality and axon regeneration in the mice lacking in the enzymes synthesizing chondroitin sulfate (2012)
  • Author(s): Kosei Takeuchi
  • Organizer: 2nd Annual Conference of COST action ECMNet
  • Place of Presentation: Barcelona, Spain
  • Invited
• [Presentation] Ｃｒｅ／ｌｏｘＰ組換え依存の標的遺伝子ノックダウン誘導のためのレンチウイルスベクターシステム (2012)
  • Author(s): 松下夏樹、松下佐知、武内恒成、八十島安伸、東山繁樹
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] コンドロイチン硫酸はマウス視覚野においてＯｔｘ２取り込みと臨界期可塑性を制御する (2012)
  • Author(s): 候旭濱、武内恒成、五十嵐道弘、杉山清佳
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] コンドロイチン硫酸の発現制御による神経再生機構 (2012)
  • Author(s): 武内恒成、比嘉進、吉岡望、渡部裕美、川嵜麻実、和田芳野、五十嵐道弘
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] コンドロイチン硫酸合成酵素ＫＯマウスにおける機能解析 (2011)
  • Author(s): 武内 恒成
  • Organizer: 第30回日本糖質科学会年会(招待講演)
  • Place of Presentation: ハイブ長岡（新潟県）
• [Presentation] Brain development abnormality and axon regeneration in the mice lacking in the enzymes synthesizing chondroitin sulfate (2011)
  • Author(s): 武内 恒成
  • Organizer: 8th IBRO World Congress of Neurosciences
  • Place of Presentation: Fortezza de Basso Convention, (Florence, Italy)
• [Presentation] Cre/loxP 相同組換えに依存するＲＮＡｉ誘導ベクターの構築と評価 (2011)
  • Author(s): 松下 夏樹
  • Organizer: 第3回日本ＲＮＡｉ研究会大会
  • Place of Presentation: グランドプリンス広島（広島県）
• [Presentation] Development of lentiviral vector systems for conditional gene knockdown induced by Cre/loxP recombination (2011)
  • Author(s): 松下 夏樹
  • 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）
• [Presentation] コンドロイチン硫酸合成に関する遺伝子改変マウスの神経系発生解析 (2011)
  • Author(s): 武内 恒成
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館（京都府）
• [Presentation] コンドロイチン硫酸合成酵素ノックアウトマウスは脊髄損傷回復が早い (2011)
  • Author(s): 武内 恒成
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 山代温泉瑠璃光（石川県）
• [Presentation] Mice lacking in an enzyme involved in chondroitin sulfate synthesis shows better recovery from spinal cord injury. (2011)
  • Author(s): 武内 恒成
  • Organizer: Annual Meeting of Society for Neuroscience 2011
  • Place of Presentation: Walter E Washington Convention Center, (Washington DC, USA)
• [Book] 遺伝子導入プロトコール-発現解析とRNAi実験-(編集企画を担当及び分担執筆(武内恒成) (2012)
  • Author(s): 仲嶋一範、北村義浩、武内恒成
  • Total Pages: 251
  • Publisher: 羊土社
• [Book] 遺伝子導入プロトコール －発現解析とRNAi実験－ (2012)
  • Author(s): 仲嶋一範、北村義浩、武内恒成 （3者共同編著）
  • Total Pages: 252
  • Publisher: 羊土社
• [Remarks] 新聞報道 (新潟日報 朝日新聞など)2013年11月13日
• [Remarks] プレスリリース記事
  • URL: http://www.med.niigata-u.ac.jp/bc2/news/press.pdf
• [Remarks] 教室研究成果
  • URL: http://www.med.niigata-u.ac.jp/bc2/study/index.html
• [Patent(Industrial Property Rights)] 神経再生発生を可視化する抗リン酸化抗体 (2014)
  • Inventor(s): 武内恒成
  • Industrial Property Rights Holder: 武内恒成
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-04-18
  • Overseas
• [Patent(Industrial Property Rights)] 抗GAP43抗体 (2012)
  • Inventor(s): 武内恒成 河嵜麻実 五十嵐道弘
  • Industrial Property Rights Holder: 新潟大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-10-19
  • Overseas
• [Patent(Industrial Property Rights)] GAP43抗体 (2011)
  • Inventor(s): 五十嵐 道弘、武内 恒成
  • Industrial Property Rights Holder: 新潟大学
  • Industrial Property Number: 2011-230577
  • Filing Date: 2011