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 proper differentiation. Furthermore, it is known that reactive oxygen species (ROS) are generated during the process of alcohol metabolism (Wu & Cederbaum, 2009), and the inflammasome pathway has been implicated as a factor in a signaling response to a double challenge (Cullen, Kearney, Clancy, & Martin, 2015). This raises the possibility that alcohol induced activation of the inflammasome pathway in iPS cells and NPCs would cause an increased sensitivity to a second “hit” or insult. This is precisely the case where a second insult in combination with alcohol pre-exposure enhances the innate immune response, resulting in an increase of neuroinflammation. These data suggest that alcohol exposure in iPS cells and NPCs causes an increased sensitivity to ROS, and this could potentially contribute to the pathophysiology of neurogenesis in humans. Taken together, neuronal inflammation may add to the pathophysiology of AUDs via the induction of the inflammasome pathway.
