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Chunk #55 — 5. Cell-type specific effects of alcohol in human brain tissue

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Gene expression profiling in the human alcoholic brain.
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As mentioned in the preceding section, alcohol may differentially target cell types across brain regions. Analysis of human frontal cortex, central nucleus of the amygdala, and basolateral amygdala revealed discrete effects of alcohol on different cell types in these regions (Ponomarev et al., 2012). The basolateral amygdala showed the most changes in cell-type composition, and the frontal cortex showed the fewest. The neuronal and microglial distributions in the amygdalar regions were inversely shifted, suggesting a decrease in the number of neurons and an increase in microglia. Similarly, analysis of the nucleus accumbens and hippocampus revealed that alcohol differentially targets cell types in these regions (Mamdani et al., 2015; McClintick et al., 2013). Neuronal expression modules were negatively correlated with lifetime alcohol consumption, while astrocytic and microglial expression modules were positively correlated. Again, this suggested a loss of neuronal function in tandem with astrocytic and microglia activation in brain tissue from human alcoholics. This is consistent with literature showing a general degradation of neurons as well as activation and proliferation of microglia after chronic alcohol exposure (Crews et al., 2011), which