CD38 is critical for social behaviour by regulating oxytocin secretion

被引：511

作者：

Jin, Duo

Liu, Hong-Xiang

Hirai, Hirokazu

Torashima, Takashi

Nagai, Taku

Lopatina, Olga

Shnayder, Natalia A.

Yamada, Kiyofumi

Noda, Mami

Seike, Toshihiro

Fujita, Kyota

Takasawa, Shin

Yokoyama, Shigeru

Koizumi, Keita

Shiraishi, Yoshitake

Tanaka, Shigenori

Hashii, Minako

Yoshihara, Toru

Higashida, Kazuhiro

Islam, Mohammad Saharul

Yamada, Nobuaki

Hayashi, Kenshi

Noguchi, Naoya

Kato, Ichiro

Okamoto, Hiroshi

Matsushima, Akihiro

Salmina, Alla

Munesue, Toshio

Shimizu, Nobuaki

Mochida, Sumiko

Asano, Masahide

Higashida, Haruhiro ^{[1
]}

机构：

[1] Kanazawa Univ, 21st Century COE Program Innovat Brain Sci & Dev, Kanazawa, Ishikawa 9208640, Japan

[2] Kanazawa Univ, Grad Sch Med, Dept Cellular Neurophysiol, Kanazawa, Ishikawa 9208640, Japan

[3] Kanazawa Univ, Grad Sch Med, Dept Biophys Genet, Kanazawa, Ishikawa 9208640, Japan

[4] Kanazawa Univ, Grad Sch Med, Dept Anat, Kanazawa, Ishikawa 9208640, Japan

[5] Kanazawa Univ, Adv Sci Res Ctr, Kanazawa, Ishikawa 9208640, Japan

[6] Japan Sci & Technol Agcy, SORST, Kanazawa, Ishikawa 9208640, Japan

[7] Kanazawa Univ, Sch Nat Sci & Technol, Lab Neuropsychopharmacol, Kanazawa, Ishikawa 9201192, Japan

[8] Kanazawa Univ, Inst Nat & Environm Technol, Kanazawa, Ishikawa 9201192, Japan

[9] Kyushu Univ, Grad Sch Pharmaceut Sci, Lab Pathophysiol, Fukuoka 8128582, Japan

[10] Tohoku Univ, Grad Sch Med, Dept Biochem, Sendai, Miyagi 9808575, Japan

[11] Tohoku Univ, Grad Sch Med, Dept Adv Biol Sci Regenerat, Sendai, Miyagi 9808575, Japan

[12] Kanazawa Univ Hosp, Cent Clin Lab, Kanazawa, Ishikawa 9208641, Japan

[13] Kanazawa Univ Hosp, Dept Psychiat, Kanazawa, Ishikawa 9208641, Japan

[14] Toyama Univ, Sch Med, Dept Biochem, Toyama 9300194, Japan

[15] Nanao Natl Hosp, Nanao 9208531, Japan

[16] Krasnoyarsk State Med Acad, Dept Med Chem & Biochem, Krasnoyarsk 660022, Russia

[17] Tokyo Med Univ, Dept Physiol, Tokyo, Japan

来源：

NATURE | 2007年 / 446卷 / 7131期

关键词：

D O I：

10.1038/nature05526

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：41 / 45

页数：5

共 44 条

[1] Central control of penile erection: Role of the paraventricular nucleus of the hypothalamus [J].