Blood and brain gene expression signatures of chronic intermittent ethanol consumption in mice.

Autor: Ferguson LB; Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas, United States of America.; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, Texas, United States of America.; Department of Neuroscience, University of Texas at Austin, Austin, Texas, United States of America., Roberts AJ; Animal Models Core Facility, The Scripps Research Institute, San Diego, California, United States of America., Mayfield RD; Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas, United States of America.; Department of Neuroscience, University of Texas at Austin, Austin, Texas, United States of America., Messing RO; Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas, United States of America.; Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, Texas, United States of America.; Department of Neuroscience, University of Texas at Austin, Austin, Texas, United States of America.
Jazyk: angličtina
Zdroj: PLoS computational biology [PLoS Comput Biol] 2022 Feb 17; Vol. 18 (2), pp. e1009800. Date of Electronic Publication: 2022 Feb 17 (Print Publication: 2022).
DOI: 10.1371/journal.pcbi.1009800
Abstrakt: Alcohol Use Disorder (AUD) is a chronic, relapsing syndrome diagnosed by a heterogeneous set of behavioral signs and symptoms. There are no laboratory tests that provide direct objective evidence for diagnosis. Microarray and RNA-Seq technologies enable genome-wide transcriptome profiling at low costs and provide an opportunity to identify biomarkers to facilitate diagnosis, prognosis, and treatment of patients. However, access to brain tissue in living patients is not possible. Blood contains cellular and extracellular RNAs that provide disease-relevant information for some brain diseases. We hypothesized that blood gene expression profiles can be used to diagnose AUD. We profiled brain (prefrontal cortex, amygdala, and hypothalamus) and blood gene expression levels in C57BL/6J mice using RNA-seq one week after chronic intermittent ethanol (CIE) exposure, a mouse model of alcohol dependence. We found a high degree of preservation (rho range: [0.50, 0.67]) between blood and brain transcript levels. There was small overlap between blood and brain DEGs, and considerable overlap of gene networks perturbed after CIE related to cell-cell signaling (e.g., GABA and glutamate receptor signaling), immune responses (e.g., antigen presentation), and protein processing / mitochondrial functioning (e.g., ubiquitination, oxidative phosphorylation). Blood gene expression data were used to train classifiers (logistic regression, random forest, and partial least squares discriminant analysis), which were highly accurate at predicting alcohol dependence status (maximum AUC: 90.1%). These results suggest that gene expression profiles from peripheral blood samples contain a biological signature of alcohol dependence that can discriminate between CIE and Air subjects.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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