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CD38 is critical for social behaviour by regulating oxytocin secretion

Nature 446, 41–45 (01 March 2007) | Download Citation

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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.

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Acknowledgements

We acknowledge support from the COE programme of the Japanese Ministry of Education, Culture, Sports, Science and Technology. We thank D. A. Brown for discussion.

Author Contributions All authors contributed to this paper; in particular, K.Y., S.T., H.O. and A.S. contributed to experimental planning, and H. Higashida, H. Hirai and A.M. performed experimental work and project planning.

Author information

    • Duo Jin
    • , Hong-Xiang Liu
    •  & Hirokazu Hirai

    These authors contributed equally to this work.

Affiliations

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

    • Duo Jin
    • , Hong-Xiang Liu
    • , Hirokazu Hirai
    • , Olga Lopatina
    • , Natalia A. Shnayder
    • , Kiyofumi Yamada
    • , Shigeru Yokoyama
    • , Keita Koizumi
    • , Toru Yoshihara
    • , Mohammad Saharul Islam
    • , Nobuaki Yamada
    • , Masahide Asano
    •  & Haruhiro Higashida

  2. Department of Biophysical Genetics, and,

    • Duo Jin
    • , Hong-Xiang Liu
    • , Olga Lopatina
    • , Natalia A. Shnayder
    • , Shigeru Yokoyama
    • , Keita Koizumi
    • , Minako Hashii
    • , Kazuhiro Higashida
    • , Mohammad Saharul Islam
    • , Kenshi Hayashi
    •  & Haruhiro Higashida

  3. Department of Anatomy, and,

    • Yoshitake Shiraishi
    •  & Shigenori Tanaka

  4. Department of Cellular Neurophysiology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan

    • Takashi Torashima
    •  & Haruhiro Higashida

  5. Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan

    • Hirokazu Hirai
    • , Takashi Torashima
    • , Keita Koizumi
    • , Toru Yoshihara
    • , Nobuaki Yamada
    •  & Masahide Asano

  6. SORST, Japan Science and Technology Agency (JST), Kanazawa 920-8640, Japan

    • Hirokazu Hirai

  7. Laboratory of Neuropsychopharmacology, School of Natural Science and Technology, and

    • Taku Nagai
    •  & Kiyofumi Yamada

  8. Institute of Nature and Environmental Technology, Kanazawa University, Kanazawa 920-1192, Japan

    • Nobuaki Shimizu

  9. Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan

    • Mami Noda
    • , Toshihiro Seike
    •  & Kyota Fujita

  10. Department of Biochemistry, and,

    • Shin Takasawa
    •  & Naoya Noguchi

  11. Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

    • Hiroshi Okamoto

  12. Central Clinical Laboratory, and,

    • Kenshi Hayashi

  13. Department of Psychiatry, Kanazawa University Hospital, Kanazawa 920-8641, Japan

    • Toshio Munesue

  14. Department of Biochemistry, Toyama University School of Medicine, Toyama 930-0194, Japan

    • Ichiro Kato

  15. Nanao National Hospital, Nanao 920-8531, Japan

    • Akihiro Matsushima

  16. Department of Biochemistry and Medical Chemistry, Krasnoyarsk State Medical Academy, Krasnoyarsk 660022, Russia

    • Alla Salmina

  17. Department of Physiology, Tokyo Medical University, Tokyo 160-8402, Japan

    • Sumiko Mochida

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Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Corresponding authors

Correspondence to Hirokazu Hirai or Haruhiro Higashida.

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DOI

https://doi.org/10.1038/nature05526

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