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.
authors.affiliation: Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan.
authors.forename: Duo
authors.initials: D
authors.lastname: Jin
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Liu
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
authors.forename: Takashi
authors.initials: T
authors.lastname: Torashima
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.forename: Olga
authors.initials: O
authors.lastname: Lopatina
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Shnayder
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Mami
authors.initials: M
authors.lastname: Noda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Seike
authors.forename: Kyota
authors.initials: K
authors.lastname: Fujita
authors.forename: Shin
authors.initials: S
authors.lastname: Takasawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Keita
authors.initials: K
authors.lastname: Koizumi
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Shigenori
authors.initials: S
authors.lastname: Tanaka
authors.forename: Minako
authors.initials: M
authors.lastname: Hashii
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshihara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Higashida
authors.forename: Mohammad Saharul
authors.initials: MS
authors.lastname: Islam
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yamada
authors.forename: Kenshi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Naoya
authors.initials: N
authors.lastname: Noguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsushima
authors.forename: Alla
authors.initials: A
authors.lastname: Salmina
authors.forename: Toshio
authors.initials: T
authors.lastname: Munesue
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shimizu
authors.forename: Sumiko
authors.initials: S
authors.lastname: Mochida
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Higashida
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000647:Amnesia / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007267:Injections; D008297:Male; D008425:Maternal Behavior / Q000502:physiology*; D008568:Memory / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D010121:Oxytocin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D012919:Social Behavior; D014667:Vasopressins / Q000097:blood
chemical_list: D014667:Vasopressins; D010121:Oxytocin; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium