Microglia play a critical role in the synaptic pruning process [23], and alterations in their normal function have been shown to disrupt proper developmental synaptic pruning [49]. In our study, alcohol consumption led to morphologic changes in microglia and changes in surface marker expression (Fig. 5). Also, the lysosomal protein CD68 was downregulated in the hippocampal microglia. Thus, the effect of alcohol on microglia is significant and may lead to altered microglial phagocytic function. An interesting future direction would be to assess synaptic pruning in this model. There is also evidence that proinflammatory cytokines may have an influence on synapse function, much like complement involvement in the regulation of synapse development. For example, TNFα has been shown to modulate glutamate receptors and decrease synaptic strength [50–52]. Interestingly, while the resident source is likely from the microglia, peripheral macrophages also express TNFα and may be involved in influencing synapses in addition to their possible role promoting neuroinflammation [52, 53]. Additionally, we noted increased cytokine protein expression in the hippocampus (Fig. 4), and cytokines have been implicated in synapse dysregulation in hippocampus
