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CD38 is critical for social behaviour by regulating oxytocin secretion

Author

Listed:
  • Duo Jin

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    and)

  • Hong-Xiang Liu

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    and)

  • Hirokazu Hirai

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan
    SORST, Japan Science and Technology Agency (JST), Kanazawa 920-8640, Japan)

  • Takashi Torashima

    (Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
    Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan)

  • Taku Nagai

    (Laboratory of Neuropsychopharmacology, School of Natural Science and Technology, and)

  • Olga Lopatina

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    and)

  • Natalia A. Shnayder

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    and)

  • Kiyofumi Yamada

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    Laboratory of Neuropsychopharmacology, School of Natural Science and Technology, and)

  • Mami Noda

    (Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan)

  • Toshihiro Seike

    (Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan)

  • Kyota Fujita

    (Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan)

  • Shin Takasawa

    (and)

  • Shigeru Yokoyama

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    and)

  • Keita Koizumi

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    and
    Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan)

  • Yoshitake Shiraishi

    (and)

  • Shigenori Tanaka

    (and)

  • Minako Hashii

    (and)

  • Toru Yoshihara

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan)

  • Kazuhiro Higashida

    (and)

  • Mohammad Saharul Islam

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    and)

  • Nobuaki Yamada

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan)

  • Kenshi Hayashi

    (and
    Central Clinical Laboratory, and,)

  • Naoya Noguchi

    (and)

  • Ichiro Kato

    (Toyama University School of Medicine, Toyama 930-0194, Japan)

  • Hiroshi Okamoto

    (Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan)

  • Akihiro Matsushima

    (Nanao National Hospital, Nanao 920-8531, Japan)

  • Alla Salmina

    (Krasnoyarsk State Medical Academy, Krasnoyarsk 660022, Russia)

  • Toshio Munesue

    (Kanazawa University Hospital, Kanazawa 920-8641, Japan)

  • Nobuaki Shimizu

    (Institute of Nature and Environmental Technology, Kanazawa University, Kanazawa 920-1192, Japan)

  • Sumiko Mochida

    (Tokyo Medical University, Tokyo 160-8402, Japan)

  • Masahide Asano

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan)

  • Haruhiro Higashida

    (Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
    and
    Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan)

Abstract

CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders.

Suggested Citation

  • Duo Jin & Hong-Xiang Liu & Hirokazu Hirai & Takashi Torashima & Taku Nagai & Olga Lopatina & Natalia A. Shnayder & Kiyofumi Yamada & Mami Noda & Toshihiro Seike & Kyota Fujita & Shin Takasawa & Shiger, 2007. "CD38 is critical for social behaviour by regulating oxytocin secretion," Nature, Nature, vol. 446(7131), pages 41-45, March.
  • Handle: RePEc:nat:nature:v:446:y:2007:i:7131:d:10.1038_nature05526
    DOI: 10.1038/nature05526
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    Citations

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    Cited by:

    1. Tetsushi Sadakata & Yo Shinoda & Akira Sato & Hirotoshi Iguchi & Chiaki Ishii & Makoto Matsuo & Ryosuke Yamaga & Teiichi Furuichi, 2013. "Mouse Models of Mutations and Variations in Autism Spectrum Disorder-Associated Genes: Mice Expressing Caps2/Cadps2 Copy Number and Alternative Splicing Variants," IJERPH, MDPI, vol. 10(12), pages 1-19, November.
    2. Maria Gerasimenko & Olga Lopatina & Anna A Shabalova & Stanislav M Cherepanov & Alla B Salmina & Shigeru Yokoyama & Hisanori Goto & Hiroshi Okamoto & Yasuhiko Yamamoto & Katsuhiko Ishihara & Haruhiro , 2020. "Distinct physical condition and social behavior phenotypes of CD157 and CD38 knockout mice during aging," PLOS ONE, Public Library of Science, vol. 15(12), pages 1-17, December.

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