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Chunk #28 — Current Work Attempting to Use iPS Cell Technology to Model AUDs — Alcohol’s impact on GABAA receptor function in human neurons

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Using human stem cells as a model system to understand the neural mechanisms of alcohol use disorders: Current status and outlook.
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Modeling the effect of alcohol exposure in vitro on human subject-derived neuronal cells is beneficial in that it captures the role of human genetic variability in influencing both the acute alcohol response as well as the development and progression of the human disease state in a disease relevant system (Lieberman et al., 2017). Lieberman et al. detected an increase in mRNA expression levels of GABRA1, GABRG2 and GABRD in iPS cell derived neuronal cells following chronic alcohol exposure (21 days at a concentration of 50 mM). GABRA1 and GABRG2 were increased in both control and AUD donors, while GABRD was only upregulated in AUD cell lines. However, work performed using in vitro and in vivo animal models have reported variable results in GABAA receptor subunit expression levels following chronic alcohol exposure. Contradictions in data between animal and human models could be due to differences in cell-type and/or brain regions. Whole-cell patch clamp recordings were used to assess the effect of alcohol exposure on GABAA evoked currents, but no effect was observed on the electrophysiological properties measured. Taken together, the study