All-trans retinoic acid upregulates reduced CD38 transcription in lymphoblastoid cell lines from autism spectrum disorder

Mathias Riebold, David Mankuta, Elad Lere, Salomon Israel, Songfa Zhong, Luba Nemanov, Mikhail V. Monakhov, Shlomit Levi, Nurit Yirmiya, Maya Yaari, Fabio Malavasi, Richard P. Ebstein

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)799-806
Number of pages8
JournalMolecular Medicine
Volume17
Issue number7-8
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Riebold, M., Mankuta, D., Lere, E., Israel, S., Zhong, S., Nemanov, L., Monakhov, M. V., Levi, S., Yirmiya, N., Yaari, M., Malavasi, F., & Ebstein, R. P. (2011). All-trans retinoic acid upregulates reduced CD38 transcription in lymphoblastoid cell lines from autism spectrum disorder. Molecular Medicine, 17(7-8), 799-806. https://doi.org/10.2119/molmed.2011.00080