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Chunk #30 — Discussion

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Transcriptome analysis of alcohol-treated microglia reveals downregulation of beta amyloid phagocytosis.
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In our studies, alcohol exposure reduced phagocytosis of Aβ with no effect on uptake of polystyrene beads (unpublished findings, DLF). Aβ phagocytosis is regulated by various proteins several of which were identified as being induced by alcohol treatment. In primary microglia, activation of SIRPb1 (signal regulatory protein beta-1) increased phagocytosis of fibrillary Aβ, as well as of microsphere beads [80]. In contrast, inhibition of CLIC1 (chloride intracellular ion channel) increased Aβ phagocytosis, possibly via suppression of pro-inflammatory cytokine or iNOS induction [81], while inhibition had no effect on bead uptake. The basis for this difference is not known, but may be related to the ability of Aβ but not polystyrene beads to induce microglia cytokine production, which in turn regulates phagocytotic activities.