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Chunk #15 — Results

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Stress-response pathways are altered in the hippocampus of chronic alcoholics.
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Large fold changes were found among genes associated with inflammatory and immune response (GO:0006954 and GO:0006955), particularly interleukin receptors (Table 1A). Twenty-one genes involved in hypoxia (GO:0001666) were differentially expressed, with two-thirds of them showing higher expression in the brains of alcoholics (Table 1B). The expression of most genes in the glucocorticoid pathway, including the glucocorticoid receptor (NR3C1) and 2 FK506 binding proteins (FKBP4, FKBP5), differed significantly between alcoholics and controls. NR3C1 expression was 30% lower in alcoholics, whereas FKBP5, which functions as a negative regulator of the pathway, was increased over 2-fold (Table 1C). Genes related to myelination and oligodendrocytes demonstrated decreased expression in the alcoholic hippocampi (Table 1D). Fourteen of 16 significantly changed genes in this group were expressed at lower levels in alcoholics, averaging 74%, whereas only 2 were at higher levels. Eight metallothioneins (MT) with an FDR ≤ 20% were expressed at higher levels in the hippocampus of alcoholics (mean 1.44-fold), and 9 more (20% < FDR ≤ 40%) were also expressed at higher levels in alcoholics (mean 1.2-fold; Table 1E).