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Chunk #24 — 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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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 (NR2B subunit) and GRIN2D (NR2D subunit) in human iPS cell-derived neural cultures from alcoholic and non-alcoholic donors in response to 0 or 50 mM chronic alcohol treatment. Neural cultures produced from alcoholic donors displayed a significant increase for GRIN1 (and a trend towards significance for GRIN2B) mRNA levels in response to chronic alcohol exposure. The work described above, (Lieberman et al., 2012), suggests that human iPS cell-derived neural cells could potentially provide scientists with a powerful tool to model and assay the molecular underpinnings that alter NMDA receptor function and subunit expression to acute and chronic alcohol exposure, which still to this day are not completely understood.