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 IslamNobuaki Yamada, Kenshi Hayashi, Naoya Noguchi, Ichiro Kato, Hiroshi Okamoto, Akihiro Matsushima, Alla Salmina, Toshio Munesue, Nobuaki Shimizu, Sumiko Mochida, Masahide Asano, Haruhiro Higashida

Research output: Contribution to journalArticle

424 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)41-45
Number of pages5
JournalNature
Volume446
Issue number7131
DOIs
Publication statusPublished - 01-03-2007

All Science Journal Classification (ASJC) codes

  • General

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    Jin, D., Liu, H. X., Hirai, H., Torashima, T., Nagai, T., Lopatina, O., Shnayder, N. A., Yamada, K., Noda, M., Seike, T., Fujita, K., Takasawa, S., Yokoyama, S., Koizumi, K., Shiraishi, Y., Tanaka, S., Hashii, M., Yoshihara, T., Higashida, K., ... Higashida, H. (2007). CD38 is critical for social behaviour by regulating oxytocin secretion. Nature, 446(7131), 41-45. https://doi.org/10.1038/nature05526