Several groups have previously used human iPSC‐derived neuron cultures to study cellular phenotypes of individuals with AUD, 26 , 32 assessing the effects of acute or chronic ethanol exposure. 33 , 34 , 35 In a transcriptomic study of iPSC‐derived forebrain‐like neurons from healthy and alcohol‐dependent individuals, Jensen and colleagues 35 found that sustained exposure (7 days) to 50 mM ethanol affects genes involved in cholesterol homeostasis, notch signaling, and cell cycle pathways. A different study showed that 7 days of 50 mM ethanol suppressed the NMDA‐R response to acute ethanol in healthy neurons, while receptor subunit mRNA expression levels were only altered in neurons differentiated from individuals with alcohol dependence. 33 Longer exposure to the same ethanol concentrations (21 days) led to increased NMDA‐R expression in iPSC‐derived neurons from alcohol‐dependent, but not from healthy individuals. 34 Both 24 h and 7‐day exposure to 70 mM ethanol also activate the NLRP3 inflammasome pathway in iPSC‐derived neural progenitors. 36
