Gene expression profiling in the human alcoholic brain

Abstract

Long-term alcohol use causes widespread changes in gene expression in the human brain. Aberrant gene expression changes likely contribute to the progression from occasional alcohol use to alcohol use disorder (including alcohol dependence). Transcriptome studies have identified individual gene candidates that are linked to alcohol-dependence phenotypes. The use of bioinformatics techniques to examine expression datasets has provided novel systems-level approaches to transcriptome profiling in human postmortem brain. These analytical advances, along with recent developments in next-generation sequencing technology, have been instrumental in detecting both known and novel coding and non-coding RNAs, alternative splicing events, and cell-type specific changes that may contribute to alcohol-related pathologies. This review offers an integrated perspective on alcohol-responsive transcriptional changes in the human brain underlying the regulatory gene networks that contribute to alcohol dependence.

The role of neuroimmune signaling in alcoholism

“…First, they regulate the stability of target mRNAs in the cytosol via formation of an RNA-induced silencing complex (RISC) and binding to the 3′-untranslated region of mRNA (Ambros, 2004; Bartel, 2004; Czech and Hannon, 2011). The role of microRNAs as transcriptional regulators in alcoholism is discussed by Warden and Mayfield in their article in this special edition (Warden and Mayfield, 2017). Another newly identified mechanism whereby ethanol modulates immune activation is through the extracellular release of miRNA (Turchinovich et al, 2013).…”

Allele-Specific Expression and High-Throughput Reporter Assay Reveal Functional Variants in Human Brains with Alcohol Use Disorders

“…Alcohol use disorders (AUDs) are major public health problems [1][2][3]. Alcohol is a central nervous system depressant, and high levels of consumption over a long period may alter brain function to promote AUDs and damage the brain, in part by altering gene expression levels [4,5]. Understanding the molecular mechanisms by which alcohol affects the brain is important and might provide clues to the causes of AUDs and ways to reverse the impact on the brain of heavy drinking.…”

Chronic intermittent ethanol exposure selectively alters the expression of Gα subunit isoforms and RGS subtypes in rat prefrontal cortex

“…Dysregulation of neurotransmission in the PFC is associated with learning and memory deficits and subsequent loss of control of drinking behavior in alcoholics (Moselhy et al , 2001). Microarray and RNA-seq studies indicate that the expression of numerous genes involved in receptor function and receptor-mediated G-protein signaling are altered in the frontal cortex of human alcoholics (Lewohl et al , 2000, Mayfield et al , 2002, Warden & Mayfield, 2017). These changes likely mediate adaptive changes in neuronal function in response to alcohol exposure.…”