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Chunk #20 — Results — Chronic alcohol exposure regulates GABAA subunit gene expression

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Examining the effects of alcohol on GABA receptor mRNA expression and function in neural cultures generated from control and alcohol dependent donor induced pluripotent stem cells.
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Neural cultures derived from 13 CTL and 9 AD neural cell lines were exposed to neural differentiation media or media containing 50 mM alcohol for 21 days, with media replaced daily. We examined mRNA expression of GABAA subunit-encoding genes GABRA1, GABRG2, and GABRD. Two-way repeated measures ANOVA revealed significant effects of alcohol treatment on GABRA1 [F(1,40)= 19.9, p < 0.001] GABRG2 [F(1,40)= 13.8, p < 0.01], and GABRD [F(1,40)= 4.6, p < 0.05] gene expression (Figure 1D–F). No significant main effect of donor status was observed for any of the three genes (p’s > 0.05). There was no significant interaction between alcohol treatment and donor status for GABRA1 or GABRG1 (p’s > 0.05), while a modestly significant interaction was observed for GABRD [F(1,40) = 4.2, p = 0.054], such that average gene expression was unchanged in control-derived cultures and increased in alcoholic-derived neural cultures by 24%. The 3- to 8-fold range in basal expression among iPSC lines (Figure 1D–F) could reflect different rates of neural maturation of individual lines and/or individual differences in donor genome between lines. The variation in