GDNF protects against alcohol-mediated cell death in culture but is reduced in response to alcohol along with neurite outgrowth (Barak, Carnicella, Yowell, & Ron, 2011; Carnicella, Kharazia, Jeanblanc, Janak, & Ron, 2008; Chen & Charness, 2012). Interestingly, GDNF has been used to prevent relapse of alcohol consumption (Carnicella et al., 2008). Thus, it is unclear if PAE is preventing or enhancing the differentiation program; these mixed results may derive from the fact that differentiation occurred in vitro from NPCs derived in vivo after PAE. Indeed, alcohol increases differentiation at the expense of proliferation under some conditions (Kim et al., 2010); as such, the effects we have observed from differentiated NPC cultures may occur due to a combined effect of PAE and culture conditions.
