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Chunk #31 — Discussion

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Pilot study of iPS-derived neural cells to examine biologic effects of alcohol on human neurons in vitro.
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The objective of this study was to explore the potential utility of human iPS cells as a model to examine the biological actions of alcohol on human neural cells. We found that NMDA receptor function and mRNA expression in human iPS-derived neural cells responded to acute and chronic alcohol exposure similarly in several respects to that seen in rodent models. Specifically, acute exposure attenuated the NMDA but not AMPA receptor response, consistent with previous findings (Puglia and Valenzuela, 2010, Nie et al., 1994, Nagy, 2004, Dodd et al., 2000). In contrast we did not observe acute alcohol enhancement of GABAA responses, which has been observed in some, but not all, reports of alcohol effects in dissociated cell rodent cultures (Kumar et al., 2009, Yamashita et al., 2006). GABAA responses to acute alcohol may in part be dependent on indirect effects of alcohol on GABAA receptors mediated by neuroactive steroids (Sanna et al., 2004). We also observed that 7-day alcohol exposure significantly increased NMDA receptor subunit mRNA expression, which parallels previous findings in rodent models (Nagy, 2008b, Hu et al., 1996,