Exon Microarray Analysis of Human Dorsolateral Prefrontal Cortex in Alcoholism

Abstract

Background Alcohol abuse is associated with cellular and biochemical disturbances that impact upon protein and nucleic acid synthesis, brain development, function and behavioral responses. To further characterize the genetic influences in alcoholism and the effects of alcohol consumption on gene expression, we used a highly sensitive exon microarray to examine mRNA expression in human frontal cortex of alcoholics and control males. Methods Messenger RNA was isolated from the dorsolateral prefrontal cortex (dlPFC, Brodmann area 9) of 7 adult Alcoholic (6 males, 1 female, mean age 48 years) and 7 matched controls. Affymetrix Human Exon 1.0 ST Array was performed according to standard procedures and the results analyzed at the gene level. Microarray findings were validated using qRT-PCR, and the ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA). Results Decreased mRNA expression was observed for genes involved in cellular adhesion (e.g., CTNNA3, ITGA2), transport (e.g., TF, ABCA8), nervous system development (e.g., LRP2, UGT8, GLDN) and signaling (e.g., RASGRP, LGR5) with influence over lipid and myelin synthesis (e.g., ASPA, ENPP2, KLK6). IPA identified disturbances in network functions associated with neurological disease, and development including cellular assembly and organization impacting on psychological disorders. Conclusions Our data in alcoholism support a reduction in expression of dlPFC mRNA for genes involved with neuronal growth, differentiation and signaling that targets white matter of the brain.

Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells

“…Fold change and p -values were calculated for genes that were differentially expressed in vitamin D treated proliferation, post-proliferation and differentiation vs. control (vehicle treated) groups. Fold change statistics for individual genes were derived based on previously published statistical methods [88,89]. Each treatment and control group consisted of biological triplicates for analysis.…”

Gene expression profiling in the human alcoholic brain

“…miRNAs were significantly up-regulated in the frontal cortex of human alcoholics (Lewohl et al, 2011; Manzardo et al, 2014; Nunez and Mayfield, 2012), and may have roles in apoptosis, cell cycle regulation, cell adhesion, oligodendrocyte proliferation, synaptic transmission, ion channel function, and immune signaling based on functional classification of predicted target genes (Nunez and Mayfield, 2012). Predicted target mRNAs of up-regulated miRNAs were significantly over-represented among alcohol-induced down-regulated mRNAs (Lewohl et al, 2011; Nunez and Mayfield, 2012), suggesting a role for miRNA-dependent inhibition of gene expression in human alcoholics.…”

Multiplex Immunoassay of Plasma Cytokine Levels in Men with Alcoholism and the Relationship to Psychiatric Assessments

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