Chronic ethanol consumption alters monocyte transcriptional program by modifying chromatin accessibility

Sureshchandra, Suhas; Rais, Maham; Stull, Cara; Grant, Kathleen A.; Messaoudi, Ilhem

doi:10.1016/j.alcohol.2016.10.034

Cited by 2 publications

(14 citation statements)

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“…Transcriptome studies in the alcohol research field have revealed that alcohol use affects the expression patterns of hundreds of mRNAs and ncRNAs in the brain tissue of humans and animal models, e.g., see reviews and primary research articles (Contet, 2012;Nunez and Mayfield, 2012;Mayfield, 2017;Warden and Mayfield, 2017;Ferguson et al, 2019;Brenner et al, 2020;Drake et al, 2020). In addition to brain tissue, some studies have explored alcohol's effects in peripheral tissues including blood and saliva (Beech et al, 2012(Beech et al, , 2014Hicks et al, 2012;Kupfer et al, 2013;McClintick et al, 2014McClintick et al, , 2019Ignacio et al, 2015;Barr et al, 2016;Sureshchandra et al, 2016Sureshchandra et al, , 201910.3389/fnmol.2022.1032362 Ten Berg et al, 2018;Rosato et al, 2019;Lewis et al, 2021;Liu et al, 2021;Mead et al, 2021;Ferguson et al, 2022;Gong et al, 2022). These studies will be detailed in the following sections.…”

Section: Transcriptome Backgroundmentioning

confidence: 99%

“…Ten studies measured mRNA levels in peripheral tissues (Beech et al, 2012(Beech et al, , 2014Hicks et al, 2012;Kupfer et al, 2013;McClintick et al, 2014McClintick et al, , 2019Barr et al, 2016;Sureshchandra et al, 2016Sureshchandra et al, , 2019Ferguson et al, 2022). Only one of these studies included a measure of biomarker performance (Ferguson et al, 2022).…”

Section: Mrnamentioning

confidence: 99%

“…Three studies have performed a transcriptome analysis using peripheral blood mononuclear cells (PBMCs) from rhesus macaque monkeys after chronic voluntary ethanol intake (Barr et al, 2016;Sureshchandra et al, 2016Sureshchandra et al, , 2019. Although these studies did not test the ability of these transcriptional changes to serve as distinguishing biomarkers (likely because of the low sample sizes), PCA clearly distinguished the transcriptional profiles of ethanol naïve and ethanol-consuming animals, with less separation between moderate and heavy ethanol consumers than between ethanol consumers and controls (Sureshchandra et al, 2016(Sureshchandra et al, , 2019. This suggests that ethanol consumption is a main driver of PBMC gene expression variability and that the PBMC transcriptome would be useful in distinguishing ethanol-consuming and ethanol-naïve monkeys.…”

Section: Intermittent Accessmentioning

confidence: 99%

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RNA biomarkers for alcohol use disorder

Ferguson

Mayfield

Messing

2022

Front. Mol. Neurosci.

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Alcohol use disorder (AUD) is highly prevalent and one of the leading causes of disability in the US and around the world. There are some molecular biomarkers of heavy alcohol use and liver damage which can suggest AUD, but these are lacking in sensitivity and specificity. AUD treatment involves psychosocial interventions and medications for managing alcohol withdrawal, assisting in abstinence and reduced drinking (naltrexone, acamprosate, disulfiram, and some off-label medications), and treating comorbid psychiatric conditions (e.g., depression and anxiety). It has been suggested that various patient groups within the heterogeneous AUD population would respond more favorably to specific treatment approaches. For example, there is some evidence that so-called reward-drinkers respond better to naltrexone than acamprosate. However, there are currently no objective molecular markers to separate patients into optimal treatment groups or any markers of treatment response. Objective molecular biomarkers could aid in AUD diagnosis and patient stratification, which could personalize treatment and improve outcomes through more targeted interventions. Biomarkers of treatment response could also improve AUD management and treatment development. Systems biology considers complex diseases and emergent behaviors as the outcome of interactions and crosstalk between biomolecular networks. A systems approach that uses transcriptomic (or other -omic data, e.g., methylome, proteome, metabolome) can capture genetic and environmental factors associated with AUD and potentially provide sensitive, specific, and objective biomarkers to guide patient stratification, prognosis of treatment response or relapse, and predict optimal treatments. This Review describes and highlights state-of-the-art research on employing transcriptomic data and artificial intelligence (AI) methods to serve as molecular biomarkers with the goal of improving the clinical management of AUD. Considerations about future directions are also discussed.

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Section: Transcriptome Backgroundmentioning

confidence: 99%

Section: Mrnamentioning

confidence: 99%

Section: Intermittent Accessmentioning

confidence: 99%

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RNA biomarkers for alcohol use disorder

Ferguson

Mayfield

Messing

2022

Front. Mol. Neurosci.

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“…Drinking classifications were defined as chronic moderate drinking (CMD) or chronic heavy drinking (CHD) based on 12 months of ethanol self-administration (tissue and drinking data obtained from the Monkey Alcohol Tissue Research Resource: www.matrr.com). These cohorts of animals (Cohorts 4, 5, 6a, 6b, 7a, 7b, 10a, and 14 on matrr.com) were described in two previous studies of peripheral immune system response to alcohol (24,25). Blood plasma was isolated by centrifugation over histopaque (Sigma, St Louis, MO) as per manufacturer's protocol and stored at -80C until they could be analyzed as a batch.…”

Section: Animal Studies and Sample Collectionmentioning

confidence: 99%

“…This model allows for elucidation of the impact of chronic alcohol consumption in an outbred species while avoiding confounding factors such as smoking or drug use. Using this model, we have reported large transcriptomic changes in peripheral blood mononuclear cells (PBMC) and tissue resident macrophages with alcohol consumption (24,25). These studies revealed altered expression of genes associated with host defense, inflammation, and wound repair (26,27).…”

Section: Introductionmentioning

confidence: 99%

Exploratory extracellular vesicle-bound miRNA profiling to identify candidate biomarkers of chronic alcohol drinking in non-human primates

Lewis

Doratt

Sureshchandra

et al. 2021

Preprint

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Background: Long-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it is challenging to determine whether alcohol use should be considered a risk factor during diagnosis and treatment. We lack reliable biomarkers of alcohol use that could be used to determine drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNA (EV-miRNA) have been discovered to be consistent biomarkers of conditions including cancer and liver disease. Methods: In this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 non-human primates after 12 months of voluntary ethanol drinking. Results: We identified a list of up- and downregulated EV-miRNA candidate biomarkers of both heavy drinking as well as those positively correlated with ethanol dose. We further overexpressed these candidate miRNA in control primary peripheral immune cells to assess potential functional mechanisms of these EV-miRNA. We identified that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased inflammatory TNFA; or IL-6 production in PBMC after stimulation. Conclusion: This exploratory study identified several EV-miRNA that could serve as biomarkers of long-term alcohol drinking as well as provided a mechanism for alcohol-induced peripheral inflammation.

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Chronic ethanol consumption alters monocyte transcriptional program by modifying chromatin accessibility

Cited by 2 publications

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RNA biomarkers for alcohol use disorder

RNA biomarkers for alcohol use disorder

Exploratory extracellular vesicle-bound miRNA profiling to identify candidate biomarkers of chronic alcohol drinking in non-human primates

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