CD38 is critical for social behaviour by regulating oxytocin secretion

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, Shigeru Yokoyama, Keita Koizumi, Yoshitake Shiraishi, Shigenori Tanaka, Minako Hashii, Toru Yoshihara, Kazuhiro Higashida, Mohammad Saharul Islam, Nobuaki Yamada, Kenshi Hayashi, Naoya Noguchi, Ichiro Kato, Hiroshi Okamoto, Akihiro Matsushima, Alla Salmina, Toshio Munesue, Nobuaki Shimizu, Sumiko Mochida, Masahide Asano and Haruhiro Higashida ()
Additional contact information
Duo Jin: Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
Hong-Xiang Liu: Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
Hirokazu Hirai: Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
Takashi Torashima: Kanazawa University Graduate School of Medicine, 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
Natalia A. Shnayder: Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
Kiyofumi Yamada: Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
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
Keita Koizumi: Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, 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
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
Nobuaki Yamada: Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan
Kenshi Hayashi: 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
Haruhiro Higashida: Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan

Nature, 2007, vol. 446, issue 7131, 41-45

Abstract: 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.

Date: 2007
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DOI: 10.1038/nature05526

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