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Chunk #23 — Results — Alcohol induces morphologic changes and alters expression of activation markers in microglia that are partially restored by CCR2/5 inhibition

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Chronic alcohol-induced neuroinflammation involves CCR2/5-dependent peripheral macrophage infiltration and microglia alterations.
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Activated microglia often assume an amoeboid morphology that is characterized by shortened cell processes and an enlarged soma. We used immunofluorescent staining of the microglial marker IBA1 to investigate if chronic alcohol induces morphological changes in line with an activated cell shape (Fig. 5a). We focused on hippocampal microglia specifically because of the significant infiltration of peripheral CCR2RFP macrophages to this region (Fig. 2c) suggested this as a site of active neuroinflammation. We found that chronic alcohol tended to increase the cell soma size of microglia (Fig. 5b). Inhibiting CCR2/5 signaling with CVC significantly reduced the soma in chronic alcohol-fed mice with 3 weeks of CVC treatment (Fig. 5b). Chronic alcohol significantly reduced the process length of hippocampal microglia, and CVC administration did not affect this morphology compared to chronic alcohol-fed mice (Fig. 5c). These data indicate that chronic alcohol induces a more reactive cell morphology than in pair-fed control mice and CCR2/5 inhibition modestly restores a normal cell body.