after PAE has not been studied extensively. Additionally, A2A activation leads to upregulation of VEGF expression, suggesting that the decreased mRNA levels of both of these genes after PAE may be connected in the proliferating NPC culture conditions (Escudero et al., 2013). Further, gestational alcohol exposure alters cortical vascularization in the neonatal brain resulting in reduced expression of VEGF receptors (Jégou et al., 2012). Vascularization, neural development, cell growth, and proliferation are dependent on the oscillatory signaling of Notch pathway components; as such, reduced expression of Hes1 after PAE may alter proliferation of the NPC culture (Barton & Fendrik, 2013; Fischer et al., 2004; Shimojo, Ohtsuka, & Kageyama, 2011). Other studies have demonstrated the sensitivity of Notch signaling to alcohol using several different exposure methods: these include application of 100 mM alcohol on human neural stem cells in vitro (Hashimoto-Torii et al., 2011; Melendez, McGinty, Kalivas, & Becker, 2012) and chronic intermittent (Melendez et al., 2012) or acute in vivo exposure to high doses of alcohol (Rubert, Miñana, Pascual, & Guerri, 2006). Maternal alcohol consumption from E7–E21 in the rat model (25% v/v alcohol) has been shown to reduce proliferation and induce rapid differentiation via down-regulation of Notch pathway factors
