Neuron Enriched Exosomal MicroRNA Expression Profiles as a Marker of Early Life Alcohol Consumption
Year: 2023
Type: preprint
Study design: Observational Study
Abstract: Background: Alcohol consumption may impact and shape brain development through perturbed biological pathways and impaired molecular functions. We investigated the relationship between alcohol consumption rates and neuron-enriched exosomal microRNA (miRNA) expression to better understand the impact of alcohol use on early life brain biology. Methods: Neuron-enriched exosomal miRNA expression was measured from plasma samples collected from young people using a commercially available microarray platform while alcohol consumption was measured using the Alcohol Use Disorders Identification Test. Linear regression and network analyses were used to identify significantly differentially expressed miRNAs and to characterize the implicated biological pathways, respectively. Results: Compared to alcohol naïve controls, young people reporting high alcohol consumption exhibited significantly higher expression of four neuron-enriched exosomal miRNAs including miR-30a-5p, miR-194-5p, and miR-339-3p, although only miR-30a-5p and miR-194-5p survived multiple test correction. The miRNA-miRNA interaction network inferred by a network inference algorithm did not detect any differentially expressed miRNAs with a high cutoff on edge scores. However, when the cutoff of the algorithm was reduced, five miRNAs were identified as interacting with miR-194-5p and miR-30a-5p. These seven miRNAs were associated with 25 biological functions; miR-194-5p was the most highly connected node and was highly correlated with the other miRNAs in this cluster. Conclusions: Our observed association between neuron-enriched exosomal miRNAs and alcohol consumption concurs with results from experimental animal models of alcohol use and suggests that high rates of alcohol consumption during the adolescent/young adult years may impact brain functioning and development by modulating miRNA expression.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Virginia Commonwealth University, Commonwealth Health Research Board, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Cancer Institute, National Center for Advancing Translational Sciences
Awards: Genetic Contributions of Negative Valence Systems to Internalizing Pathways, Center for Clinical and Translational Research, Collaborative Research: Dynamics of surfactant - amyloid-beta protein interactions during self-assembly, Cross-species investigation of gene networks for ethanol-related behaviors, Massey Cancer Center - Cancer Center Support Grant
OpenAlex ID: W4380272523