The proliferation capacity of patient-derived iPS cells and NPCs were unaffected by either acute (24 hours) or prolonged (7 days) exposure to alcohol (70 mM). However, alcohol exposure was observed to prime an innate immune-like response via activation of NLRP3 (NOD-like receptor family pyrin domain containing 3) damage sensing inflammasome pathway. Activation of the inflammasome pathway led to an accumulation of microtubule-associated protein 1A/1B-light chain 3+ (LCB3+) autophagic puncta, as well as a deficiency in the distribution of lysosomes and mitochondria. This is in agreement with previous work describing cross talk between the inflammasome pathway and mitochondrial/lysosomal machinery (Salminen, Kaarniranta, & Kauppinen, 2012). In addition, progenitor cells exposed to alcohol prior to differentiation resulted in a significant decrease in the generation of mature neurons, when compared to an untreated isogenic control. This is an extremely important finding when analyzed in the context of fetal alcohol exposure. It has been shown that in utero alcohol exposure disrupts the development of the embryo and fetus, and we believe that the use of iPS cells may have uncovered the impact of alcohol on
