Role of miRNAs from mesenchymal stem cell-derived extracellular vesicles in neuroinflammation and behavioral impairments induced by chronic alcohol consumption in female mice.

JOURNAL/nrgr/04.03/01300535-202606000-00050/figure1/v/2026-02-11T151048Z/r/image-tiff Mesenchymal stem cell-derived extracellular vesicles have emerged as a promising form of regenerative and immunomodulatory therapy; indeed, micro (mi)RNAs contained within mesenchymal stem cell-derived extracellular vesicles modulate target gene expression and impact disease-associated pathways. Chronic alcohol consumption leads to neuroinflammation, brain damage, and impaired cognition. Evidence indicates that females are more vulnerable to alcohol-induced damage than males. While mesenchymal stem cell-derived extracellular vesicles have been studied in various neuroinflammatory conditions, their potential to counteract alcohol-induced brain damage remains unclear. In this study, we investigated whether repeated intravenous administration of mesenchymal stem cell-derived extracellular vesicles could ameliorate neuroinflammation and behavioral impairment induced by chronic alcohol consumption in female mice. Mesenchymal stem cell-derived extracellular vesicles diminished the increased binding of a micro-positron emission tomography tracer ( 18 F-FDG) when analyzing whole-brain 3D images and brain coronal sections of ethanol-treated mice. Mesenchymal stem cell-derived extracellular vesicle administration protected against ethanol-induced proinflammatory gene upregulation, cognitive dysfunction, and the conditioned rewarding effects of cocaine. MiRNA sequencing data from mesenchymal stem cell-derived extracellular vesicles revealed the elevated expression of extracellular vesicle-derived miR-483-5p and miR-140-3p in the brains of ethanol-treated female mice following mesenchymal stem cell-derived extracellular vesicle administration. In addition, mesenchymal stem cell-derived extracellular vesicles modulated the expression of pro-inflammatory-related miRNA target genes (e.g., Socs3 , Tnf , Mtor , and Atf6 ) in the brains of ethanol-treated female mice. These results suggest that mesenchymal stem cell-derived extracellular vesicles could function as a neuroprotective therapy to ameliorate the neuroinflammation, cognitive dysfunction, and conditioned rewarding effects of cocaine associated with chronic alcohol consumption.