that high-PRS microglial cells may play a crucial role in shaping synaptic connectivity through a process known as microglia-dependent synapse elimination, specifically in high-PRS individuals, potentially rendering them at higher risk for developing/maintaining AUD. A mouse study (28) has shown that long-term alcohol exposure activates microglia to phagocytose synapses, leading to impaired synaptic plasticity and cognitive function (47). Nevertheless, the interactions with heterogeneous neuronal populations in various brain regions further emphasize their diverse contributions to neuronal homeostasis and behavioral regulation, which may be involved in AUD pathophysiology (79). Consequently, our results imply that the heightened phagocytic activity observed in high-PRS microglial cells after ethanol exposure may exert a considerable influence on synaptic connectivity and remodeling, potentially affecting neuronal function in the context of AUD-related dementia.
