Following intermittent ethanol exposure, we found that high-PRS and low-PRS microglial cells rapidly transition from their default branched profile (66) to a more amoeboid state (67). Microglia with high-PRS showed a significant decrease in fractal dimension and a pronounced increase in circularity compared to their low-PRS counterparts after ethanol exposure. Further gene expression profiling revealed ethanol exposure alters notable DEGs in high-PRS and low-PRS microglial cells, with more than half of the DEGs overlapping. The up-regulated genes in high-PRS were enriched for processes related to peptide antigen assembly with the MHCII protein complex and antigen processing and presentation, as well as phagocytosis. Microglia, functioning as antigen-presenting cells, are equipped with phagocytic receptors that facilitate the capture of antigens. These antigens undergo processing within phagosomes and are subsequently presented by MHCII and costimulatory molecules expressed in microglia (68, 69). The whole process could modulate the immune responses within the central nervous system during AUD.
