Chunk #15 — Introduction — 1. Epigenetic Regulation due to Histone Covalent Modifications — 1B. Alcohol and Histone Acetylation and Deacetylation Mechanisms in the Brain
anxiety-like behaviors (Pandey, Ugale, et al., 2008; Pandey, Zhang, et al., 2008) (Figure 2). The neurotrophin BDNF (brain-derived neurotrophic factor), a critical modulator of synaptic plasticity and a downstream target gene of CREB, has also been implicated in the comorbidity of alcoholism and anxiety (Pandey, Zhang, Roy, & Misra, 2006; Poo, 2001). BDNF activity via CREB phosphorylation regulates activity regulated cytoskeleton-associated protein (Arc) and dendritic spine density and we showed that this pathway was positively regulated during acute ethanol exposure (anxiolysis) and negatively regulated during withdrawal from chronic ethanol exposure (anxiety-like behaviors) (Moonat, Sakharkar, Zhang, & Pandey, 2011; Pandey, Zhang, et al., 2008). Ethanol exposure has been shown to decrease CBP expression and histone acetylation in the developing cerebellum and this presumably is responsible for the motor deficits associated with fetal alcohol spectrum disorders (Guo et al., 2011). In summary, these findings clearly implicate the functional importance of CREB signaling pathways in anxiety and alcohol use disorders.
