GABRB3 gene expression increases upon ethanol exposure in human embryonic stem cells

Abstract

Ionotropic receptors are the target for most mood-defining compounds. Chronic exposure to ethanol (EtOH) alters receptor-mediated responses and the numbers of these channels and specific subunits; as well as induces anxiolytic, sedative, and anesthetic activity in the human brain. However, very little is known regarding the effects of EtOH on ionotropic receptor transcription during early human development (preimplantation). Using two separate human embryonic stem cell lines the study shows that low amounts of EtOH (20 mM) alters transcription of the ionotropic subunit GABRB3. Changes in ionotrophic receptor expression influence the central nervous system development and have been shown to produce brain abnormalities in animal models. These results suggest that low concentrations of EtOH can alter ionotropic receptor transcription during early human development (preimplantation), which may be a contributing factor to the neurological phenotypes seen in fetal alcohol spectrum disorder (FASD).

Keywords::

• Ionotropic receptors
• gene expression
• ethanol exposure
• early development
• human embryonic stem cells

Acknowledgments

Special recognition is extended to Saju Samuel, Chief Operations Officer for Jeevan Biosciences, Inc., for administrative support and the Emory Biomarker Service Center-IANAFS. MK, BAG, CDS, JHM, FG, RJN, JA, SNU, CDE, SLS, and RJN performed experiments and/or analyzed the data. All authors contributed to the project’s planning and writing of the manuscript. RJN supervised the project.

Declaration of interest

This work was funded in part by Emory University Department of Anesthesiology and Jeevan Biosciences, Inc.