Extracellular vesicles’ MicroRNA expression profiles as a marker of early life alcohol consumption

Alcohol consumption, particularly during adolescence and young adulthood, has long been associated with potential effects on brain development. However, the precise mechanisms underlying this relationship have remained elusive. In a groundbreaking study, researchers at Virginia Commonwealth University delved into microRNA (miRNA) expression within neuron-enriched extracellular vesicles (EVs) to shed light on the impact of alcohol use on early-life brain biology.

Using plasma samples collected from young individuals, the researchers measured the expression of miRNAs within neuron-enriched EVs—a promising avenue for understanding the molecular intricacies of brain function. Simultaneously, participants’ alcohol consumption levels were assessed using the Alcohol Use Disorders Identification Test.

MiRNA-miRNA interaction network inference

Fig. 4

A Inferred miRNA-miRNA interaction network. This network consists of 16 miRNAs and 77 edges and two clusters. B Inferred miRNA-miRNA interaction network after dropping the twin participants. This network consists of 13 miRNAs and 69 edges and two clusters. C Differentially expressed miRNAs and their direct regulators consist of seven miRNAs. D Functional analysis of the seven miRNAs from (C) comprising two differentially expressed miRNAs and their direct regulators The count represents the number of miRNAs within a set associated with a specific pathway. 25 biological functions are statistically significant. E Correlation between differentially expressed miRNAs and their direct regulators. miR-194-5p is highly correlated with the other miRNAs in this cluster.

The results revealed intriguing associations between alcohol consumption rates and the expression of specific neuron-enriched EVs’ miRNAs. Young individuals reporting high alcohol consumption exhibited significantly elevated expression levels of three miRNAs: miR-30a-5p, miR-194-5p, and miR-339-3p. Among these, miR-30a-5p and miR-194-5p stood out as particularly noteworthy, showcasing consistent differences even after rigorous statistical correction.

Furthermore, network analyses unveiled intricate interactions among these miRNAs, hinting at their collective role in modulating biological functions within the brain. Notably, miR-194-5p emerged as a central node within this network, demonstrating strong correlations with other miRNAs and implicating its pivotal role in alcohol-induced alterations in brain functioning and development.

These findings align with previous research conducted in experimental animal models, further substantiating the link between alcohol consumption and miRNA-mediated changes in brain biology. By elucidating the impact of alcohol on miRNA expression within neuron-enriched EVs, this study offers valuable insights into the molecular mechanisms underlying the effects of alcohol on brain development during crucial developmental stages.

Moving forward, continued exploration of miRNA dynamics in response to alcohol consumption holds immense promise for advancing our understanding of brain health and informing strategies for mitigating the potential adverse effects of alcohol on cognitive function and mental well-being, particularly among young individuals.

Yakovlev V, Lapato DM, Rana P, Ghosh P, Frye R, Roberson-Nay R. (2024) Neuron enriched extracellular vesicles’ MicroRNA expression profiles as a marker of early life alcohol consumption. Transl Psychiatry 14(1):176. [article]

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