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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.

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Figure 1: Nurturing behaviour is impaired in CD38 -/- mothers.
Figure 2: Social recognition deficit in CD38 -/- male mice.
Figure 3: Oxytocin and vasopressin concentrations.
Figure 4: Oxytocin secretion and calcium signalling.

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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.

Author Contributions All authors contributed to this paper; in particular, K.Y., S.T., H.O. and A.S. contributed to experimental planning, and H. Higashida, H. Hirai and A.M. performed experimental work and project planning.

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Correspondence to Hirokazu Hirai or Haruhiro Higashida.

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Jin, D., Liu, HX., Hirai, H. et al. CD38 is critical for social behaviour by regulating oxytocin secretion. Nature 446, 41–45 (2007). https://doi.org/10.1038/nature05526

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