As mentioned previously, release of pro-inflammatory cytokines produces widespread effects on surrounding neurons and synaptic function. For example, IL-1β release could interact with ethanol’s effects on GABAergic signaling in brain regions important for addiction, such as the CeA (Bajo et al., 2014, 2015). In vitro work demonstrates that microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity in a TLR7-dependent manner (Coleman et al., 2017). Microglia are also fundamental to normal CNS processes, such as neurogenesis (Gemma and Bachstetter, 2013), activity-dependent synaptic pruning (Schafer et al., 2012), and excitatory synaptic maturation and function (Miyamoto et al., 2013; Yuwen Wu et al., 2015). For example, microglia control neuronal firing through release of brain-derived neurotrophic factor and other regulators of synaptic plasticity (Ferrini and De Koninck, 2013). They surround the soma of highly active neurons to decrease firing (Li et al., 2012) and also migrate to and displace inhibitory synapses in cortical neurons to increase neuronal expression of neuroprotective molecules (Chen et al., 2014). Thus, changes in microglia activity may impair normal neuronal activity and exacerbate ethanol-induced neurotoxicity through different neuroimmune molecules (Fig. 1).
