P.1.005 Retinoic acid upregulates reduced cd38 transcription in lymphoblastoid cell lines from patients with autism spectrum disorder

Riebold, Mathias; Mankuta, David; Malavasi, Fabio; Lerer, Elad; Levi, Shlomit; Yirmiya, Nurit; Ebstein, Richard P.

doi:10.1016/s0924-977x(11)70006-2

Cited by 6 publications

(15 citation statements)

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“…The reduction in CD38 expression is more marked in female ASD subjects than in male ASD subjects. These first results [69] have now been partially replicated in a new study from our laboratory [72]. In the new expanded study there was no effect of gender.…”

Section: Molecular Genetic Association [71]mentioning

confidence: 70%

“…These considerations prompted us to measure CD38 gene expression in lymphoblastoid cell lines (LBC) derived from both ASD subjects and unaffected parents. We also include in the gene expression and family-based association analysis the SNP (rs3796863), which proved significantly associated with ASD in the Munesue et al [72] study.…”

Section: Cd38 and Autism Spectrum Disordersmentioning

confidence: 99%

“…In our subsequent investigation [72], we have re-analyzed the EBV lines described in the first report, significantly adding to the sample with 38 new cell lines so that in the second investigation for each proband both of their parents were now included in the analysis. Cells in culture, or frozen lines were first thawed, and then cultured, and their CD38 mRNA levels measured.…”

Section: Molecular Genetic Association [71]mentioning

confidence: 99%

“…their parents at least in the disease model currently adopted and using immortalized cell lines [69,72].…”

Section: Molecular Genetic Association [71]mentioning

confidence: 99%

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Are retinoids potential therapeutic agents in disorders of social cognition including autism?

et al. 2011

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Edited by Sergio Papa, Gianfranco Gilardi and Wilhelm JustKeywords: Autism spectrum disorder (ASD) All-trans retinoic acid (ATRA) CD38 Oxytocin Polymorphism a b s t r a c t Increasing evidence suggests that the nonapeptide, oxytocin (OT), helps shape social and affiliative behaviors not only in lower mammals but also in humans. Recently, an essential mediator of brain OT release has been discovered, ADP-ribosyl cyclase and/or CD38. We have subsequently shown that polymorphisms across the CD38 gene are associated with autism spectrum disorders (ASD). Notably, CD38 expression in lymphoblastoid cells (LBC) is reduced in cell lines derived from ASD subjects compared to parental cell lines. Intriguingly, a correlation was observed between CD38 expression and measures of social function in ASD. Finally, we have shown that all-trans retinoic acid (ATRA), a known inducer of CD38 transcription, can rescue low CD38 expressing LBC lines derived from ASD subjects and restore normal levels of transcription of this ectoenzyme providing 'proof of principle' in a peripheral model that retinoids are potential therapeutic agents in ASD. Ó 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. OxytocinClassically, the nonapeptide oxytocin (OT) has been viewed as a hypothalamic neuropeptide that is released into the general circulation from the neural lobe of the pituitary, inducing uterine contractions during parturition and milk ejection during lactation. OT is derived from a pre-prohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the posterior pituitary for storage and subsequent release into the bloodstream (see [1] for comprehensive review of the oxytocin receptor system). OT and social behaviorBeyond the long-known peripheral effects of OT, a wealth of animal studies have elaborated the role of OT, or their analogues such as isotocin and vasotocin [2], in molding social behavior from fish to mammals [3]. In the past few years the role of OT has also been examined in our own species, and similar to what has been learned from animal studies, it appears that this nonapeptides also influence social behaviors in humans [4,5]. Indeed, OT has been suggested as the 'great facilitator of life' in a recent review [6].In humans, intranasal administration of OT has been shown to increase trust [7], facilitate mind-reading [8], enhance human memory for social identity [9], increase positive communication between couples [10], increase gaze to the eye region [11] and increase generosity [12]. Intriguingly, OT plasma levels have been linked to individual patterns of maternal-fetal attachment [13] and salivary OT levels were associated with bonding to own parents and inversely related to psychological distress, particularly depressive symptoms [14]. Social anxiety symptom severity, adjusted for age and gender in a healthy group of subjects, was associated with higher plasma oxytocin levels [15]. Imaging studies reinforce the role of OT in influencing human social ...

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Section: Molecular Genetic Association [71]mentioning

confidence: 70%

Section: Cd38 and Autism Spectrum Disordersmentioning

confidence: 99%

Section: Molecular Genetic Association [71]mentioning

confidence: 99%

“…their parents at least in the disease model currently adopted and using immortalized cell lines [69,72].…”

Section: Molecular Genetic Association [71]mentioning

confidence: 99%

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Are retinoids potential therapeutic agents in disorders of social cognition including autism?

et al. 2011

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“…In addition, they suggested that retinoid could be a potential therapeutic agent to increase CD38 expression in ASD subjects (Fig. 5;Riebold et al, 2011;Ebstein, 2011). …”

Section: Human Cd38 Intronic Rs3796863 Snpmentioning

confidence: 99%

CD38 and its role in oxytocin secretion and social behavior

Higashida

Yokoyama

Kikuchi

et al. 2012

Hormones and Behavior

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Here, we review the functional roles of cyclic ADP-ribose and CD38, a transmembrane protein with ADP-ribosyl cyclase activity, in mouse social behavior via the regulation of oxytocin (OXT) release, an essential component of social cognition.Herein we describe data detailing the molecular mechanism of CD38-dependent OXT secretion in CD38 knockout mice. We also review studies that used OXT, OXT receptor (OXTR), or CD38 knockout mice. Additionally, we compare the behavioral impairments that occur in these knockout mice in relation to the OXT system and CD38.This review also examines autism spectrum disorder (ASD), which is characterized by social and communication impairments, in relation to defects in the OXT system. Two single nucleotide polymorphisms (SNPs) in the human CD38 gene are possible risk factors for ASD via inhibition of OXT function. Further analysis of CD38 in relation to the OXT system may provide a better understanding of the neuroendocrinological roles of OXT and CD38 in the hypothalamus and of the pathophysiology of ASD.3

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Social memory, amnesia, and autism: Brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38

Higashida

Yokoyama

Huang

et al. 2012

Neurochemistry International

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Previously, we demonstrated that CD38, a transmembrane protein with ADP-ribosyl cyclase activity, plays a critical role in mouse social behavior by regulating the release of oxytocin (OXT), which is essential for mutual recognition. When CD38 was disrupted, social amnesia was observed in Cd38 knockout mice. The autism spectrum disorders (ASDs), characterized by defects in reciprocal social interaction and communication, occur either sporadically or in a familial pattern. However, the etiology of ASDs remains largely unknown. Therefore, the theoretical basis for pharmacological treatments has not been established. Hence, there is a rationale for investigating single nucleotide polymorphisms (SNPs) in the human CD38 gene in ASD subjects. We found several SNPs in this gene. The SNP rs3796863 (C > A) was associated with high-functioning autism (HFA) in American samples from the Autism Gene Resource Exchange. Although this finding was partially confirmed in low-functioning autism subjects in Israel, it has not been replicated in Japanese HFA subjects. The second SNP of interest, rs1800561 (4693C > T), leads to the substitution of an arginine (R) at codon 140 by tryptophan (W; R140W) in CD38. This mutation was found in 4 probands of ASD and in family members of 3 pedigrees with variable levels of ASD or ASD traits.The plasma levels of OXT in ASD subjects with the R140W allele were lower than those in ASD subjects lacking this allele. The OXT levels were unchanged in healthy subjects with or without this mutation. One proband with the R140W allele receiving intranasal OXT for approximately 3 years showed improvement in areas of social approach, eye contact and communication behaviors, emotion, irritability, and 3 aggression. Five other ASD subjects with mental deficits received nasal OXT for various periods; three subjects showed improved symptoms, while 2 showed little or no effect. These results suggest that SNPs in CD38 may be possible risk factors for ASD by abrogating OXT function and that some ASD subjects can be treated with OXT in preliminary clinical trials.

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P.1.005 Retinoic acid upregulates reduced cd38 transcription in lymphoblastoid cell lines from patients with autism spectrum disorder

Cited by 6 publications

References 0 publications

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

CD38 and its role in oxytocin secretion and social behavior

Social memory, amnesia, and autism: Brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38

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