All-trans Retinoic Acid Upregulates Reduced CD38 Transcription in Lymphoblastoid Cell Lines from Autism Spectrum Disorder

Abstract

Deficits in social behavior in mice lacking the CD38 gene have been attributed to impaired secretion of oxytocin. In humans, similar deficits in social behavior are associated with autistic spectrum disorder (ASD), for which genetic variants of CD38 have been pinpointed as provisional risk factors. We sought to explore, in an in vitro model, the feasibility of the theory that restoring the level of CD38 in ASD patients could be of potential clinical benefit. CD38 transcription is highly sensitive to several cytokines and vitamins. One of these, all-trans retinoic acid (ATRA), a known inducer of CD38, was added during cell culture and tested on a large sample of N = 120 lymphoblastoid cell (LBC) lines from ASD patients and their parents. Analysis of CD38 mRNA levels shows that ATRA has an upmodulatory potential on LBC derived from ASD patients as well as from their parents. The next crucial issue addressed in our study was the relationship between levels of CD38 expression and psychological parameters. The results obtained indicate a positive correlation between CD38 expression levels and patient scores on the Vineland Adaptive Behavior Scale. In addition, analysis of the role of genetic polymorphisms in the dynamics of the molecule revealed that the genotype of a single-nucleotide polymorphism (rs6449182; C>G variation) in the CpG island of intron 1, harboring the retinoic-acid response element, exerts differential roles in CD38 expression in ASD and in parental LBC. In conclusion, our results provide an empirical basis for the development of a pharmacological ASD treatment strategy based on retinoids.

Effects of a Common Variant in the CD38 Gene on Social Processing in an Oxytocin Challenge Study: Possible Links to Autism

“…Correspondingly, any potential therapeutic effect of OT on social functioning in ASD is only partially mediated by the reported imaging phenotype or the underlying genotype. Apart from these constraints, very recently it has been shown that retinoids can be used to increase CD38 expression (Riebold et al, 2011) implicating a direct method to influence the CD38 system and related social cognitive deficits in autism (Ebstein et al, 2011). Finally, in this context, our findings indicate that one should take into account the individual genetic makeup when evaluating treatment effects.…”

An immunohistochemical, enzymatic, and behavioral study of CD157/BST-1 as a neuroregulator

“…It has been shown that SNPs of CD38 are associated with ASD [57–62]. As CD157 is abundant in the embryonic stages, speculation regarding an association between the SNPs of CD157 and ASD is understandable.…”

Parental Oxytocin and Early Caregiving Jointly Shape Children’s Oxytocin Response and Social Reciprocity

“…When children were 3 years old, parents' and child's salivary OT was measured and children's social reciprocity was assessed during interactions with mother, father, and their first 'best friend'. We selected SNPs on the OXTR and CD38 genes that have been linked with increased risk for disorders involving severe social dysfunction, including autism and major depression (Costa et al, 2009;Lerer et al, 2008, 2010, Riebold et al, 2011. Three hypotheses were proposed.…”