Mechanisms of proteoglycan-mediated experience-dependent neural plasticity

• Project Area: Deciphering sugar chain-based signals regulating integrative neuronal functions
• Project/Area Number: 23110002
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nagoya University
• Principal Investigator: Kadomatsu Kenji 名古屋大学, 医学(系)研究科(研究院), 教授 (80204519)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥170,820,000 (Direct Cost: ¥131,400,000、Indirect Cost: ¥39,420,000); Fiscal Year 2015: ¥31,460,000 (Direct Cost: ¥24,200,000、Indirect Cost: ¥7,260,000); Fiscal Year 2014: ¥31,460,000 (Direct Cost: ¥24,200,000、Indirect Cost: ¥7,260,000); Fiscal Year 2013: ¥33,280,000 (Direct Cost: ¥25,600,000、Indirect Cost: ¥7,680,000); Fiscal Year 2012: ¥32,890,000 (Direct Cost: ¥25,300,000、Indirect Cost: ¥7,590,000); Fiscal Year 2011: ¥41,730,000 (Direct Cost: ¥32,100,000、Indirect Cost: ¥9,630,000)
• Keywords: 糖鎖 / 神経可塑性 / 受容体 / 軸索再生 / 神経科学 / 再生医学 / 神経 / プロテオグリカン / ケラタン硫酸 / コンドロイチン硫酸

Outline of Final Research Achievements

This study was aimed at elucidating regulatory mechanisms of neural functions by sulfated glycans. Keratan sulfate inhibits axon regeneration. In a set of ocular dominance plasticity, keratan sulfate also regulates functional innervation into binocular region from non-deprived eye through regulation of LTP in the critical period. We also found that chondroitin sulfate and its receptors, PTPRσ and LAR, regulate autophagy, dystrophic endball formation and consequently axon regeneration.

Research Products

• [Int'l Joint Research] Genomics Research Center,Academia Sinica(台湾)
• [Journal Article] Keratan Sulfate Regulates the Switch from Motor Neuron to Oligodendrocyte Generation During Development of the Mouse Spinal Cord. (2016)
  • Author(s): Hashimoto H, Ishino Y, Jiang W, Yoshimura T, Takeda-Uchimura Y, Uchimura K, Kadomatsu K, Ikenaka K.
  • Journal Title: Neurochem Res. Volume: 41 Issue: 1-2 Pages: 450-462
  • DOI: 10.1007/s11064-016-1861-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A combination of keratan sulfate digestion and rehabilitation promotes anatomical plasticity after rat spinal cord injury. (2015)
  • Author(s): Ishikawa Y, Imagama S, Ohgomori T, Ishiguro N, Kadomatsu K.
  • Journal Title: Neurosci Lett. Volume: 593 Pages: 13-18
  • DOI: 10.1016/j.neulet.2015.03.015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Requirement of keratan sulfate proteoglycan phosphacan with a specific sulfation pattern for critical period plasticity in the visual cortex. (2015)
  • Author(s): Takeda-Uchimura Y, Uchimura K, Sugimura T, Yanagawa Y, Kawasaki T, Komatsu Y, Kadomatsu K.
  • Journal Title: Exp Neurol. Volume: 274 Pages: 145-155
  • DOI: 10.1016/j.expneurol.2015.08.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Keratan sulfate exacerbates experimental autoimmune encephalomyelitis. (2015)
  • Author(s): Ueno R, Miyamoto K, Tanaka N, Moriguchi K, Kadomatsu K, Kusunoki S.
  • Journal Title: J Neurosci Res. Volume: 93 Issue: 12 Pages: 1874-1880
  • DOI: 10.1002/jnr.23640
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. (2015)
  • Author(s): Foyez T, Takeda-Uchimura Y, Ishigaki S, Narentuya, Zhang Z, Sobue G, Kadomatsu K, Uchimura K.
  • Journal Title: Am J Pathol Volume: 185 Issue: 11 Pages: 3053-3065
  • DOI: 10.1016/j.ajpath.2015.07.016
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Introduction to glyco-neuroscience. (2015)
  • Author(s): Kamiguchi H, Kadomatsu K.
  • Journal Title: Exp Neurol. Volume: 274 Pages: 89-89
  • DOI: 10.1016/j.expneurol.2015.11.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Reductions of docosahexaenoic acid-containing phosphatidylcholine levels in the anterior horn of an ALS mouse model. (2015)
  • Author(s): Arima H, Omura T, Hayasaka T, Masaki N, Hanada M, Xu D, Banno T, Kobayashi K, Takeuchi H, Kadomatsu K, Matsuyama Y, Setou M.
  • Journal Title: Neuroscience. Volume: 印刷中 Pages: 127-136
  • DOI: 10.1016/j.neuroscience.2015.03.060
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Keratan sulfate expression is associated with activation of a subpopulation of microglia/macrophages in Wallerian degeneration. (2014)
  • Author(s): Shinjo R, Imagama S, Ito Z, Ando K, Nishida Y, Ishiguro N, Kadomatsu K.
  • Journal Title: Neurosci Lett. Volume: 579 Pages: 80-85
  • DOI: 10.1016/j.neulet.2014.07.018
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sulfated glycans in network rewiring and plasticity after neuronal injuries. (2014)
  • Author(s): Kadomatsu K, Sakamoto K.
  • Journal Title: Neurosci Res. Volume: 78 Pages: 50-54
  • DOI: 10.1016/j.neures.2013.10.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] KSGal6ST is essential for the 6-sulfation of galactose within keratan sulfate in early postnatal brain. (2014)
  • Author(s): Hoshino H, Foyez T, Ohtake-Niimi S, Takeda-Uchimura Y, Michikawa M, Kadomatsu K, Uchimura K.
  • Journal Title: J Histochem Cytochem. Volume: 62 Issue: 2 Pages: 145-156
  • DOI: 10.1369/0022155413511619
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chondroitin 6-O-sulfate ameliorates experimental autoimmune encephalomyelitis. (2014)
  • Author(s): Miyamoto K, Tanaka N, Moriguchi K, Ueno R, Kadomatsu K, Kitagawa H, Kusunoki S.
  • Journal Title: Glycobiology. Volume: 24 Issue: 5 Pages: 469-475
  • DOI: 10.1093/glycob/cwu014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Keratan sulfate expression in microglia is diminished in the spinal cord in experimental autoimmune neuritis. (2013)
  • Author(s): Matsui H, Ohgomori T, Natori T, Miyamoto K, Kusunoki S, Sakamoto K, Ishiguro N, Imagama S, Kadomatsu K
  • Journal Title: Cell Death Dis. Volume: 4 Issue: 12 Pages: e946-e946
  • DOI: 10.1038/cddis.2013.479
  • Peer Reviewed
• [Journal Article] Ablation of keratan sulfate accelerates early phase pathogenesis of ALS. (2013)
  • Author(s): Hirano K, Ohgomori T, Kobayashi K, Tanaka F, Matsumoto T, Natori T, Matsuyama Y, Uchimura K, Sakamoto K, Takeuchi H, Hirakawa A, Suzumura A, Sobue G, Ishiguro N, Imagama S, Kadomatsu K.
  • Journal Title: PLoS One. Volume: 8
  • NAID: 120005946841
  • Peer Reviewed
• [Journal Article] Midkine overcomes neurite outgrowth inhibition of chondroitin sulfate proteoglycan without glial activation and promotes functional recovery after spinal cord injury. (2013)
  • Author(s): Muramoto A, Imagama S, Natori T, Wakao N, Ando K, Tauchi R, Hirano K, Shinjo R, Matsumoto T, Ishiguro N, Kadomatsu K.
  • Journal Title: Neurosci Lett. Volume: 550 Pages: 150-155
  • DOI: 10.1016/j.neulet.2013.06.025
  • Peer Reviewed
• [Journal Article] CD44 expression in astrocytes and microglia is associated with ALS progression in a mouse model. (2012)
  • Author(s): Matsumoto T, Imagama S, Hirano K, Ohgomori T, Natori T, Kobayashi K, Muramoto A, Ishiguro N, Kadomatsu K.
  • Journal Title: Neurosci Lett. Volume: 520 Issue: 1 Pages: 115-120
  • DOI: 10.1016/j.neulet.2012.05.048
  • Peer Reviewed
• [Journal Article] ADAMTS-13 is produced by glial cells and upregulated after spinal cord injury. (2012)
  • Author(s): Tauchi R, Imagama S, Ohgomori T, Natori T, Shinjo R, Ishiguro N, Kadomatsu K.
  • Journal Title: Neurosci Lett. Volume: 517 Issue: 1 Pages: 1-6
  • DOI: 10.1016/j.neulet.2012.03.002
  • Peer Reviewed
• [Journal Article] The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury. (2012)
  • Author(s): Tauchi R
  • Journal Title: J Neuroinflammatio Volume: 9 Issue: 1 Pages: 53-53
  • DOI: 10.1186/1742-2094-9-53
  • Peer Reviewed
• [Journal Article] Multifaceted neuro-regenerative activities of human dental pulp stem cells promote locomotor recovery after complete transection of the rat spinal cord (2012)
  • Author(s): Kiyoshi Sakai, Akihito Yamamoto#, Kohki Matsubara, Shoko Nakamura, Mami Naruse (#correspondence)
  • Journal Title: The Journal of Clinical Investigation Volume: 122 Pages: 80-90
  • DOI: 10.1172/jci59251
  • Peer Reviewed
• [Journal Article] Keratan Sulfate Restricts Neural Plasticity after Spinal Cord Injury (2011)
  • Author(s): Shiro Imagama, Yukihiro Matsuyama(14番目)
  • Journal Title: J Neurosci Volume: 31 Issue: 47 Pages: 17091-17102
  • DOI: 10.1523/jneurosci.5120-10.2011
  • NAID: 120005946849
  • Peer Reviewed
• [Journal Article] Keratan sulfate and related murine glycosylation can suppress murine cartilage damage in vitro and in vivo. (2011)
  • Author(s): Hayashi M
  • Journal Title: Biochem Biophys Res Commun Volume: 409 Issue: 4 Pages: 732-7
  • DOI: 10.1016/j.bbrc.2011.05.077
  • Peer Reviewed
• [Presentation] 神経軸索再生と硫酸化糖鎖 (2016)
  • Author(s): 門松健治
  • Organizer: 第89日本薬理学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-09
• [Presentation] Sulfated glycans regulate autophagy and axon regeneration. (2016)
  • Author(s): Kadomatsu K.
  • Organizer: The 3rd International symposium on Glyco-neuroscience.
  • Place of Presentation: Awaji YUMEBUTAI (兵庫県淡路市)
  • Year and Date: 2016-01-14
• [Presentation] 軸索伸長を制御する糖鎖暗号の解読 (2015)
  • Author(s): 門松健治
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド(兵庫県神戸市)
  • Year and Date: 2015-12-01
• [Presentation] Why should we care about glycans in the brain. Society for Glycobiology (2014)
  • Author(s): Kadomatsu K.
  • Organizer: Satellite Symposium II Glycans in Neuroscience
  • Place of Presentation: Honolulu, USA
  • Year and Date: 2014-11-16 – 2014-11-19
• [Presentation] Role of Keratan sulfate and chondroitin sulfate in axon regeneration. (2014)
  • Author(s): Kadomatsu K.
  • Organizer: 4th ECMNET Conference
  • Place of Presentation: Antalya, Turkey
  • Year and Date: 2014-09-30 – 2014-10-02
• [Presentation] Roles of sulfated glycans and autophagy in dystrophic endball formation in the axonal regeneration inhibition. (2014)
  • Author(s): Kadomatsu K
  • Organizer: International symposium on Glyco-neuroscience
  • Place of Presentation: Awaji Yumebutai, Awaji
• [Presentation] Keratan sulfate and neuronal circuit reconstruction. (2013)
  • Author(s): Kadomatsu K
  • Organizer: Proteoglycans 2013
  • Place of Presentation: Frankfurt, Germany
  • Invited
• [Presentation] 糖鎖と神経の融合研究へ ～硫酸化糖鎖と神経回路再編～ (2013)
  • Author(s): 門松健治
  • Organizer: 生化学会大会シンポジウム「脳神経回路の可塑性の生化学研究：分子メカニズムから疾患まで2013
  • Place of Presentation: 横浜国際会議場、横浜市
  • Invited
• [Presentation] ケラタン硫酸プロテオグリカンと神経変性 「病態に根ざしたALSの新規治療法開発」 (2013)
  • Author(s): 門松健治
  • Organizer: 分科班平成25年度ワークショップ
  • Place of Presentation: 都市センターホテル、東京都千代田区
  • Invited
• [Presentation] 硫酸化糖鎖による神経軸索再生制御 (2013)
  • Author(s): 門松健治
  • Organizer: JCGG
  • Place of Presentation: 東北薬科大学、仙台市
  • Invited
• [Presentation] 神経糖鎖生物学研究の将来展望～糖鎖は如何にして第三の生命鎖たりうるか～ (2013)
  • Author(s): 門松健治
  • Organizer: 日本薬理学会 ランチョンセミナー
  • Place of Presentation: 福岡国際会議場、福岡
  • Invited
• [Presentation] 脳と糖鎖のはなし～糖鎖ってなんだろう～ (2013)
  • Author(s): 門松健治
  • Organizer: 名古屋大学オープンレクチャー2013
  • Place of Presentation: 名古屋大学、名古屋
  • Invited
• [Presentation] Regulation of neural plasticity by sugar chains-towards integration of glyco- and neuro-biology. (2012)
  • Author(s): Kadomatsu, K.
  • Organizer: Neuroscience 2012
  • Place of Presentation: Nagoya congress center,Nagoya
  • Invited
• [Presentation] A link between two sugar chains, keratan sulfate and chondroitin sulfate, in axonal regeneration/sprouting. (2012)
  • Author(s): Kadomatsu, K.
  • Organizer: GCOE International Symposium.
  • Place of Presentation: Hilton hotel, Nagoya
  • Invited
• [Presentation] 「神経糖鎖生物学」の目指すもの (2012)
  • Author(s): 門松健治
  • Organizer: 3領域合同シンポジウム 夏の包括脳ワークショップ
  • Place of Presentation: 仙台国際センター、仙台
  • Invited
• [Presentation] 神経回路再編 その糖鎖による制御 (2012)
  • Author(s): 門松健治
  • Organizer: 第3回名大・生理研合同シンポジウム
  • Place of Presentation: 岡崎カンファレンスセンター、岡崎
  • Invited
• [Presentation] Proteoglycans and neuronal network reconstruction. (2011)
  • Author(s): Kadomatsu, K.
  • Organizer: 7th international conference on proteoglycans
  • Place of Presentation: Sydney, Australia
  • Invited
• [Presentation] Proteoglycans and neuronal network reconstruction. (2011)
  • Author(s): Kadomatsu, K.
  • Organizer: Glycobiology Japan-Netherland joint seminar 2011
  • Place of Presentation: 名古屋大学（名古屋）
  • Invited
• [Presentation] 糖鎖による神経回路再編の制御 (2011)
  • Author(s): 門松健治
  • Organizer: 第8回日本病理学会カンファレンス
  • Place of Presentation: ホテルブエナビスタ（松本）
  • Invited
• [Book] Sugar Chains (2015)
  • Author(s): Kishida S and Kadomatsu K.
  • Total Pages: 288
  • Publisher: Springer
• [Book] Glycoscience: Biology and Medicine (2015)
  • Author(s): Kadomatsu K, Taniguchi, N., Endo, T., Hart, G.W., Seeberger, P.H., Wong, C.-H.
  • Total Pages: 1569
  • Publisher: Springer
• [Remarks] 新学術領域研究 神経糖鎖生物学
  • URL: http://shinkei-tosa.net
• [Remarks] 名古屋大学大学院医学系研究科分子生物学
  • URL: http://www.med.nagoya-u.ac.jp/biochem/
• [Remarks] 新学術研究領域 神経糖鎖生物学
  • URL: http://shnkei-tosa.net
• [Remarks] 名古屋大学大学院医学系研究科分子生物学
  • URL: http://www.med.nagoya-u.ac.jp/biochem/
• [Remarks] 新学術研究領域 神経糖鎖生物学
  • URL: http://shinkei-tosa.net/
• [Remarks] 名古屋大学大学院医学系研究科分子生物学
  • URL: http://www.med.nagoya-u.ac.jp/biochem/
• [Remarks] 新学術研究領域 神経糖鎖生物学
  • URL: http://shinkei-tosa.net/
• [Remarks] 名古屋大学大学院医学系研究科分子生物学
  • URL: http://www.med.nagoya-u.ac.jp/biochem/
• [Remarks] 新学術研究領域 神経糖鎖生物学
  • URL: http://shinkei-tosa.net/