and Sarkar 2010), microglia-conditioned media enhanced ethanol-induced apoptosis of cultured hypothalamic neurons. Interestingly, the neuronal cell death induced by microglia-conditioned media could be abolished if TNF-α was inactivated in the cultured cells, suggesting that microglial TNF-α production plays a key role in ethanol-induced neurotoxicity in developing neurons. The mechanism by which alcohol induces neuronal cell death may involve upregulation of NF-κB expression, which then stimulates release of TNF-α, resulting in neuronal apoptosis (Crews and Nixon 2009; Guadagno et al. 2013). Stimulation of the transcription factor AP-1 and release of IL-1β, IL-6, and transforming growth factor β (TGF-β1) also may contribute to alcohol-induced neuronal apoptosis (Alfonso-Loeches and Guerri 2011; Chen et al. 2006).
