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; Haruhiro Higashida

doi:10.1038/nature05526

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 journal › Article › peer-review

529 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 language	English
Pages (from-to)	41-45
Number of pages	5
Journal	Nature
Volume	446
Issue number	7131
DOIs	https://doi.org/10.1038/nature05526
Publication status	Published - 01-03-2007
Externally published	Yes

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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

@article{0388fe0b451f4017a65675d137151c64,

title = "CD38 is critical for social behaviour by regulating oxytocin secretion",

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.",

author = "Duo Jin and Liu, {Hong Xiang} and Hirokazu Hirai and Takashi Torashima and Taku Nagai and Olga Lopatina and Shnayder, {Natalia A.} and Kiyofumi Yamada and Mami Noda and Toshihiro Seike and Kyota Fujita and Shin Takasawa and Shigeru Yokoyama and Keita Koizumi and Yoshitake Shiraishi and Shigenori Tanaka and Minako Hashii and Toru Yoshihara and Kazuhiro Higashida and Islam, {Mohammad Saharul} and Nobuaki Yamada and Kenshi Hayashi and Naoya Noguchi and Ichiro Kato and Hiroshi Okamoto and Akihiro Matsushima and Alla Salmina and Toshio Munesue and Nobuaki Shimizu and Sumiko Mochida and Masahide Asano and Haruhiro Higashida",

note = "Funding Information: 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.",

year = "2007",

month = mar,

day = "1",

doi = "10.1038/nature05526",

language = "English",

volume = "446",

pages = "41--45",

journal = "Nature",

issn = "0028-0836",

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number = "7131",

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Jin, D, Liu, HX, Hirai, H, Torashima, T, Nagai, T, Lopatina, O, Shnayder, NA, Yamada, K, Noda, M, Seike, T, Fujita, K, Takasawa, S, Yokoyama, S, Koizumi, K, Shiraishi, Y, Tanaka, S, Hashii, M, Yoshihara, T, Higashida, K, Islam, MS, Yamada, N, Hayashi, K, Noguchi, N, Kato, I, Okamoto, H, Matsushima, A, Salmina, A, Munesue, T, Shimizu, N, Mochida, S, Asano, M & Higashida, H 2007, 'CD38 is critical for social behaviour by regulating oxytocin secretion', Nature, vol. 446, no. 7131, pp. 41-45. https://doi.org/10.1038/nature05526

TY - JOUR

T1 - CD38 is critical for social behaviour by regulating oxytocin secretion

AU - Jin, Duo

AU - Liu, Hong Xiang

AU - Hirai, Hirokazu

AU - Torashima, Takashi

AU - Nagai, Taku

AU - Lopatina, Olga

AU - Shnayder, Natalia A.

AU - Yamada, Kiyofumi

AU - Noda, Mami

AU - Seike, Toshihiro

AU - Fujita, Kyota

AU - Takasawa, Shin

AU - Yokoyama, Shigeru

AU - Koizumi, Keita

AU - Shiraishi, Yoshitake

AU - Tanaka, Shigenori

AU - Hashii, Minako

AU - Yoshihara, Toru

AU - Higashida, Kazuhiro

AU - Islam, Mohammad Saharul

AU - Yamada, Nobuaki

AU - Hayashi, Kenshi

AU - Noguchi, Naoya

AU - Kato, Ichiro

AU - Okamoto, Hiroshi

AU - Matsushima, Akihiro

AU - Salmina, Alla

AU - Munesue, Toshio

AU - Shimizu, Nobuaki

AU - Mochida, Sumiko

AU - Asano, Masahide

AU - Higashida, Haruhiro

N1 - Funding Information: 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.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - 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.

AB - 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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U2 - 10.1038/nature05526

DO - 10.1038/nature05526

M3 - Article

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AN - SCOPUS:33847398002

SN - 0028-0836

VL - 446

SP - 41

EP - 45

JO - Nature

JF - Nature

IS - 7131

ER -

CD38 is critical for social behaviour by regulating oxytocin secretion

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