CD38 is critical for social behaviour by regulating oxytocin secretion
CD38 is critical for social behaviour by regulating oxytocin secretion
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DOI：
10.1038/nature05526
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发表时间：
2007-03-01
期刊：
影响因子：
64.8
通讯作者：
Higashida, Haruhiro
中科院分区：
文献类型：
--
作者：
Jin, Duo;Liu, Hong-Xiang;Higashida, Haruhiro
CD 38是一种具有ADP-核糖基环化酶活性的跨膜糖蛋白，催化Ca 2+信号分子的形成，但其在神经内分泌系统中的作用尚不清楚。在这里，我们表明，成年CD 38基因敲除（CD 38（-/-））的雌性和雄性小鼠表现出显着的缺陷，在母亲的养育和社会行为，分别具有较高的运动活动。因此，在CD 38（-/-）小鼠中，催产素（OT）而非加压素的血浆水平显著降低。通过皮下注射或慢病毒载体介导的人CD 38在下丘脑中的递送来替代OT，挽救了CD 38（-/-）小鼠的社会记忆和母亲护理。在CD 38（-/-）小鼠中，催产素能神经垂体轴突终末中去极化诱导的OT分泌和Ca 2+升高被破坏;这在CD 38（+/+）小鼠中被CD 38代谢物拮抗剂模拟。这些结果表明，CD 38在神经肽释放中具有关键作用，从而严格调节母体和社会行为，并且可能是神经发育障碍的一个因素。
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.