CD38 is critical for social behaviour by regulating oxytocin secretion.
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.
Jin
Duo
D
Kanazawa University 21st Century COE Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan.
Liu
Hong-Xiang
HX
Hirai
Hirokazu
H
Torashima
Takashi
T
Nagai
Taku
T
Lopatina
Olga
O
Shnayder
Natalia A
NA
Yamada
Kiyofumi
K
Noda
Mami
M
Seike
Toshihiro
T
Fujita
Kyota
K
Takasawa
Shin
S
Yokoyama
Shigeru
S
Koizumi
Keita
K
Shiraishi
Yoshitake
Y
Tanaka
Shigenori
S
Hashii
Minako
M
Yoshihara
Toru
T
Higashida
Kazuhiro
K
Islam
Mohammad Saharul
MS
Yamada
Nobuaki
N
Hayashi
Kenshi
K
Noguchi
Naoya
N
Kato
Ichiro
I
Okamoto
Hiroshi
H
Matsushima
Akihiro
A
Salmina
Alla
A
Munesue
Toshio
T
Shimizu
Nobuaki
N
Mochida
Sumiko
S
Asano
Masahide
M
Higashida
Haruhiro
H
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
D014667:Vasopressins; D010121:Oxytocin; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium