to bring about distinct cellular outcomes (Meffert, Chang, Wiltgen, Fanselow, & Baltimore, 2003; Natoli, Saccani, Bosisio, & Marazzi, 2005). Neuroinflammation induced following chronic ethanol use and withdrawal was shown to occur via Toll-like receptor signaling (TLR4) and activation of the NF-kB pathway and glial derived proinflammatory cytokines, which was reduced in TLR4- deficient mice (−/−) (Alfonso-Loeches, Pascual-Lucas, Blanco, Sanchez-Vera, & Guerri, 2010). Interestingly, HAT activity and acetylation of histones H3 and H4 were reduced in wild-type mice undergoing withdrawal after chronic ethanol exposure. However these changes were not observed in the TLR4 (−/−) mice (Pascual, Baliño, Alfonso-Loeches, Aragón, & Guerri, 2011). These findings suggest that TLR4 signaling via alterations of chromatin structure can promote the neuroinflammatory changes observed after chronic ethanol exposure (Alfonso-Loeches et al., 2010; Pandey, 2012; Pascual et al., 2011). It has been recently shown that activation of proinflammatory cytokine signaling by ethanol is mediated by inhibition of HDAC activity. This provides a novel therapeutic option to manage the neuroinflammatory sequelae resulting from ethanol exposure (Zou and Crews, 2014).
