In order to model the pathogenesis of AUDs with limited intrinsic variability, we have focused our analysis on the effects of alcohol on cells derived from the same individual at three different stages: pluripotency (i.e. iPS cells), neurogenesis (i.e. NPCs), and terminal differentiation (i.e. post-mitotic neurons) [11]. In accordance with previous studies on postmortem human brains [15, 16], we show that neither acute (24 hours) nor prolonged (7 days) exposure to 70mM ethanol affects the proliferation or self-renewal of iPS cells or NPCs, but most likely impacts terminal differentiation and neuronal function. More importantly, we show an alteration of the mitochondrial pattern, as well as activation of the NLRP3 inflammasome pathway in these cells in response to ethanol exposure [5, 17]. This finding is consistent with the development of a remarkable neuroinflammatory environment in the brains of patients with a history of long-term alcohol dependence [4, 11, 18].
