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Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury

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  • Kosei Takeuchi

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan
    Center for Transdisciplinary Research, Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

  • Nozomu Yoshioka

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan
    Center for Transdisciplinary Research, Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan
    Laboratory of Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Tokyo 156 8506, Japan
    Doctoral and restart postdoctoral fellowship program, Japan Society for the Promotion of Science (JSPS))

  • Susumu Higa Onaga

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

  • Yumi Watanabe

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan
    Center for Transdisciplinary Research, Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan
    Doctoral and restart postdoctoral fellowship program, Japan Society for the Promotion of Science (JSPS))

  • Shinji Miyata

    (Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Kobe 658 8558, Japan)

  • Yoshino Wada

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

  • Chika Kudo

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

  • Masayasu Okada

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan
    Brain Research Institute, Niigata University, 1-757 Asahi-machi)

  • Kentaro Ohko

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan
    Graduate School of Medical and Dental Sciences, Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

  • Kanako Oda

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

  • Toshiya Sato

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

  • Minesuke Yokoyama

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

  • Natsuki Matsushita

    (Translational Research Center (TRC), Ehime University Hospital, Shitsukawa)

  • Masaya Nakamura

    (Keio University School of Medicine, 35 Shinanomachi, Tokyo 160 8582, Japan)

  • Hideyuki Okano

    (Keio University School of Medicine, 35 Shinanomachi, Tokyo 160 8582, Japan)

  • Kenji Sakimura

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

  • Hitoshi Kawano

    (Laboratory of Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Tokyo 156 8506, Japan)

  • Hiroshi Kitagawa

    (Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Kobe 658 8558, Japan)

  • Michihiro Igarashi

    (Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan
    Center for Transdisciplinary Research, Brain Research Institute, Niigata University, 1-757 Asahi-machi, Niigata 951 8510, Japan)

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 more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Notably, synthesis of heparan sulphate (HS), a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because HS-synthesis enzymes are induced in the mutant neurons. Moreover, chondroitinase ABC treatment never induces HS upregulation. Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectors of axon regeneration—an extracellular inhibitor of CS and intrinsic promoters, namely, HS-synthesis enzymes.

Suggested Citation

  • 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 & Natsu, 2013. "Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3740
    DOI: 10.1038/ncomms3740
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