Interestingly, divergent analytical approaches identified a number of common genes that were highly connected within networks (connectivity and hubs). These analyses have identified a number of neuroimmune- and cell death/survival-related pathways including ERK1/2 (mouse equivalent Mapk3, Mapk1; time-point based paring only), Bcl2 (in amygdala networks) and Srf (in prefrontal cortex networks). These identified hub genes demonstrated robust microRNA-mRNA network alterations in response to alcohol exposure. In addition, temporal analyses identified NF-kB- and Smad3-centered networks in NAC and PFC. Mitogen-activated protein kinases (Mapk3 and Mapk1) are critical components of signal transduction pathways that are involved in cell growth, adhesion, survival and differentiation [46] as well as myelination [47]. Rit1, a microRNA target dysregulated at multiple time points in each brain region, was also identified in the current study (see Table 3). This gene is dependent upon MAP kinase signaling pathways which are involved in neuritogenesis [48]. These biological functions are associated with regulation of transcription, translation, and cytoskeletal rearrangements [49]. In addition, these pathways are activated by a variety of signals including cytokines and heterotrimeric G protein coupled receptors [50]. Both
