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Chunk #18 — Discussion

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Ethanol-mediated activation of the NLRP3 inflammasome in iPS cells and iPS cells-derived neural progenitor cells.
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Although a wide array of studies has been performed on murine neural cells, controversial data have been obtained on the effects of ethanol on NSC proliferation or differentiation [3, 15, 32–34]. Whether a mouse model can mimic all aspects of human diseases is also highly controversial [35–37]. Nevertheless, in order to understand the pathophysiology of AUDs, it is imperative to elucidate the effects of ethanol on human cell function. Thus, we tested the impact of ethanol exposure on both iPS cells and NPCs derived from patients with no known history of alcoholism. Since it is virtually impossible to perfectly model the variable drinking habits and fluctuating blood alcohol concentration of an AUD patient [38], we opted to test acute (24hr) and prolonged (7d) alcohol exposure on iPS cells and NPCs. In particular, we chose to utilize an ethanol concentration of 70 mM, as this corresponds to the blood alcohol concentration of a heavy drinker, and treatments using concentrations above 100mM are known to cause a direct cytotoxic effect on the cells [38]. We chose a 24hr ethanol exposure to mimic