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Chunk #23 — Current Work Attempting to Use iPS Cell Technology to Model AUDs — Alcohol’s impact on NMDA 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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Studies performed assaying NMDA receptor function and measuring specific receptor subtype mRNA expression levels, reveals the power of using human iPS cells as a model to investigate the biological impact of alcohol on human neural cell types. The acute and chronic effects of alcohol exposure on human iPS-cell derived neural cells was investigated, specifically assaying NMDA receptor function and receptor subunit mRNA expression levels (Lieberman et al., 2012). Importantly, the responses were found to be similar to data obtained from animal models. Acute administration of alcohol (50 mM) significantly attenuated the peak amplitude of NMDA receptor mediated currents as seen with whole-cell voltage clamp recordings in iPS cell-generated neurons. Interestingly, the authors observed no attenuating effect on NMDA response if alcohol is administered chronically (50 mM alcohol applied each day for 7 days) prior to measuring acute re-exposure, in iPS cell-derived human neurons. These data, taken together, suggest that tolerance to attenuation of the NMDA response to acute alcohol exposure can be accomplished. Next, NMDA subunit mRNA expression was analyzed for the genes GRIN1 (NR1 subunit), GRIN2A (NR2A subunit), GRIN2B