The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
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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In the citing paper
“A seminal study showed that OTR and D2 receptor activation must occur concurrently for partner preference to develop in female prairie voles [66].”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [66]
In the citing paper
“In addition, research has pointed to the central role of transmembrane glycoprotein CD38 in OT neuropathways and in the release of OT from axon terminalis (Jin et al., 2007), and recent findings showed associations between plasma OT, genetic variability in the CD38 rs3796863 SNP, and the degree of reciprocity and touch between parents and their infants (Feldman et al., in press), pointing to the”
From Oxytocin during the initial stages of romantic attachment: Relations to couples’ interactive reciprocity (2012) · cites this paper as Jin et al., 2007
In the citing paper
“Blockade of D2 receptors in the NAcc shell prevented OT-mediated partner preferences, while blockade of OTR in the NAcc shell prevented D2 receptor mediated partner preferences in female prairie voles.”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [66]
In the citing paper
“Blockade of D2 receptors in the NAcc shell prevented OT-mediated partner preferences,”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [66]
In the citing paper
“Blockade of D2 receptors in the NAcc shell prevented OT-mediated partner preferences, while blockade of OTR in the NAcc shell prevented D2 receptor mediated partner preferences in female prairie voles.”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [66]
In the citing paper
“CD38 catalyzes the synthesis of the Ca2+-responsive messenger cyclic ADP-ribose (cADPR) by use of NAD+ and plays a key role in multiple physiological processes such as immunity, metabolism, inflammation, and even social behaviors (Jin et al., 2007).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Jin et al., 2007
In the citing paper
“CD38 was also reported to affect social behaviour, as was its homologue CD157 (REFS166,167)”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [166]
In the citing paper
“Mice with impaired OT release or signalling display impairments in maternal responsiveness (3,4).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [3]
In the citing paper
“The role of the OXT system has been investigated in rodent models, but uniquely using OXT-related mutant mice and giving OXT through intracerebroventricular (ICV), intraperitoneal (IP) and subcutaneous (SC) injections (Bielsky and Young, 2004;Jin et al, 2007;Popik et al, 1996;Sala et al, 2012;Sala et al, 2011;Takayanagi et al, 2005;Winslow and Insel, 2002).”
From Chronic and acute intranasal oxytocin produce divergent social effects in mice (2014) · cites this paper as Jin et al, 2007
In the citing paper
“Specifically, CD38 is involved in oxytocin secretion via Ca2+ release15”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [15]
In the citing paper
“Normal maternal behaviour is restored by peripheral oxcytocin replacement in Oxt−/− and Cd38−/−, but not Oxtr−/− mice, implying that circulating oxcytocin crosses the blood-brain barrier.”
From Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice (2019) · cites this paper as [5]
In the citing paper
“Loss of maternal nurturing and social interactive behaviours in Cd38−/− mice have been restored following peripheral administration of oxytocin, consistent with transport of peripherally administered exogenous oxytocin into brain5.”
From Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice (2019) · cites this paper as [5]
In the citing paper
“Compared to placebo, oxytocin administered to eight adolescent and adult males with FXS significantly increased overall eye gaze during a brief social interaction.59 Interestingly, lower doses of oxytocin in this sample appeared to show a greater effect than the higher administered dose, consistent with a recent study in healthy adults.60”
From Beyond the hype and hope: critical considerations for intranasal oxytocin research in autism spectrum disorder (2017) · cites this paper as [60]
In the citing paper
“recent investigations into dose-dependent effects of oxytocin on social cognition have demonstrated superior effects at lower (8 IU) doses.60”
From Beyond the hype and hope: critical considerations for intranasal oxytocin research in autism spectrum disorder (2017) · cites this paper as [60]
In the citing paper
“Initial evidence suggests that lower dose (8IU) oxytocin delivered via this device is effective in modulating aspects of emotional behaviour.60”
From Beyond the hype and hope: critical considerations for intranasal oxytocin research in autism spectrum disorder (2017) · cites this paper as [60]
In the citing paper
“In comparison with wild-type mice, CD38 -/-mice have reduced OXT levels in the plasma and cerebrospinal fluid (CSF) (Jin et al., 2007) but elevated levels in the hypothalamus and pituitary tissues.”
From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Jin et al., 2007
In the citing paper
“It is also required for normal social behavior in mice (Jin et al., 2007).”
From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Jin et al., 2007
In the citing paper
“We have recently shown that CD38 is required, as shown by the decreased formation of cADPR and by CICR, for some social behaviors in mice via the regulation of OXT secretion from the hypothalamus and pituitary (Jin et al., 2007;Higashida et al., 2010;Salmina et al., 2010).”
From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Jin et al., 2007
In the citing paper
“We used a genetic approach to re-express CD38 by infusing a virus carrying the human CD38 gene into the third ventricle of knockout mice.This procedure resulted in the normalization of the plasma and CSF OXT levels, thereby normalizing social memory (see Fig. 2 of Jin et al., 2007).”
From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Jin et al., 2007
In the citing paper
“In addition, social amnesia was not rescued by the local expression of human R140W-CD38, via a lentiviral infection, in the hypothalamus of CD38 knockout mice (Fig. 2 of Jin et al., 2007).”
From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Jin et al., 2007
In the citing paper
“The behavioral phenotype of CD38 -/-mice could be normalized by a single subcutaneous OXT injection because OXT is able to enter into the brain, probably through the blood-brain barrier (see Supplementary Fig. S7 of Jin et al., 2007).”
From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Jin et al., 2007
In the citing paper
“In contrast, CD38 -/-males showed sustained high levels of investigation at every encounter with the same female (Jin et al., 2007).”
From CD38 and its role in oxytocin secretion and social behavior (2012) · cites this paper as Jin et al., 2007
In the citing paper
“These results suggested that CD38 may have an important role in OT release in the human hypothalamus, as in the mice (Jin et al., 2007;Liu et al., 2008).”
From Two genetic variants of CD38 in subjects with autism spectrum disorder and controls (2010) · cites this paper as Jin et al., 2007
In the citing paper
“They showed that CD38 regulates OT secretion in the mouse hypothalamus and posterior pituitary, which is critical for mouse social behavior (Jin et al., 2007;Liu et al., 2008).”
From Two genetic variants of CD38 in subjects with autism spectrum disorder and controls (2010) · cites this paper as Jin et al., 2007
In the citing paper
“Moreover, social amnesia was not rescued by local re-expression of human W140-CD38 in the hypothalamus in the Cd38 null mice (Jin et al., 2007).”
From Two genetic variants of CD38 in subjects with autism spectrum disorder and controls (2010) · cites this paper as Jin et al., 2007
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Metadata
- Authors
- Jin, D., Liu, H.-X., Hirai, H., Torashima, T., Nagai, T., Lopatina, O., Shnayder, N. A., Yamada, K., Noda, M., Seike, T., Fujita, K., Takasawa, S., Yokoyama, S., Koizumi, K., Shiraishi, Y., Tanaka, S., Hashii, M., Yoshihara, T., Higashida, K., Islam, M. S., Yamada, N., Hayashi, K., Noguchi, N., Kato, I., Okamoto, H., Matsushima, A., Salmina, A., Munesue, T., Shimizu, N., Mochida, S., Asano, M., & Higashida, H.
- Affiliations
- Kanazawa University (JP)
- Kyushu University (JP)
- University of Toyama (JP)
- Tohoku University (JP)
- Nanao hospital (JP)
- Krasnoyarsk State Medical University (RU)
- Kanazawa University Hospital (JP)
- Tokyo Medical University (JP)
- Corresponding author
- Hirai, Hirokazu
- Higashida, Haruhiro
- ORCID
- Venue
- Nature
- Published
- 2007-02-07
- Volume
- 446
- Issue
- 7131
- Pages
- 41-45
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2048596172
- Cited by
- 665
- References
- 44
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 34 · 2023: 26 · 2022: 30 · 2021: 44 · 2020: 47 · 2019: 31 · 2018: 34 · 2017: 53 · 2016: 40 · 2015: 42 · 2014: 45 · 2013: 39 · 2012: 36
- FWCI
- 41.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- CD38, oxytocin secretion, social behavior, maternal behavior, ADP-ribosyl cyclase, neuropeptide release, neuroendocrine regulation, hypothalamus, neurohypophysis, calcium signaling, CD38 knockout mice, social memory, neurodevelopmental disorders
- MeSH terms
- Amnesia, Animals, Calcium, Female, Gene Expression Regulation, Humans, Injections, Male, Maternal Behavior, Memory, Motor Activity, Oxytocin, Social Behavior, Vasopressins, Calcium Signaling, Mice, ADP-ribosyl Cyclase 1
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