McClintick and colleagues 13 also studied the effects of chronic intermittent ethanol exposure (CIE; 4 h of 40 mM ethanol on four successive days, followed by 3 days without for 3 weeks; meant to reflect cycles of heavy drinking and abstinence) on a neuroblastoma cell line, SH‐SY5Y. Again, ethanol changed gene expression: of 1498 genes at FDR < 0.20, half increased and half decreased, but the changes were relatively small; only 133 genes were altered at least 1.2‐fold. Many of the altered genes were related to neuronal function (e.g., receptors, synthesis, degradation or transport of transmitters, channel subunits) or development (e.g., axon growth, synaptogenesis). CIE altered pathways related to neurogenesis and the plasticity of neurons, including axonal guidance, reelin signaling, synaptogenesis, dopamine signaling, and serotonin signaling. Ethanol also increased stress responses such as the unfolded protein response, and TGF‐β and NF‐κB signaling. Many genes involved in cholesterol biosynthesis were downregulated. Interestingly, 24 h withdrawal reduced most of the expression changes toward levels in unexposed cells. 13
