Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (6): 2370-2379.doi: 10.4103/NRR.NRR-D-24-01260

Previous Articles     Next Articles

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

Susana Mellado1, Najoua Touahri1, Sandra Montagud-Romero2, Carla Perpiñá-Clérigues1, 3, Francisco García-García3, Victoria Moreno-Manzano4, Consuelo Guerri1, Marta Rodríguez-Arias2, María Pascual1, *   

  1. 1Department of Physiology, School of Medicine and Dentistry, University of Valencia, Valencia, Spain;  2Department of Psychobiology, School of Psychology, University of Valencia, Valencia, Spain;  3Computational Biomedicine Laboratory, Príncipe Felipe Research Center, Valencia, Spain;  4Neuronal and Tissue Regeneration Laboratory, Príncipe Felipe Research Center, Valencia, Spain
  • Online:2026-06-15 Published:2026-04-17
  • Contact: María Pascual, PhD, maria.pascual@uv.es.
  • Supported by:
    This work was supported by the Spanish Ministry of Health‐Plan Nacional sobre Drogas (2023‐I024), the the Ministry of Science, Innovation and Universities/State Research Agency/10.13039/501100011033 (PID2023-146865OB-I00), Generalitat Valenciana (CIAICO/2021/203), the Primary Addiction Care Research Network (RD21/0009/0005) and FEDER Funds, GVA. 

PDF

7

Abstract: 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 (18F-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.

Key words: behavior, chronic alcohol consumption, cognitive, ethanol, extracellular vesicles, female, mesenchymal stem cells, miRNAs, neuroinflammation