{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:36:36Z","timestamp":1786649796956,"version":"build-2736575974"},"reference-count":69,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0 http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>JOURNAL\/nrgr\/04.03\/01300535-202606000-00050\/figure1\/v\/2026-04-16T195327Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>\n                    Mesenchymal stem cell\u2013derived extracellular vesicles have emerged as a promising form of regenerative and immunomodulatory therapy; indeed, micro (mi)RNAs contained within mesenchymal stem cell\u2013derived 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\u2013derived 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\u2013derived extracellular vesicles could ameliorate neuroinflammation and behavioral impairment induced by chronic alcohol consumption in female mice. Mesenchymal stem cell\u2013derived extracellular vesicles diminished the increased binding of a micro-positron emission tomography tracer (\n                    <jats:sup>18<\/jats:sup>\n                    F-FDG) when analyzing whole-brain 3D images and brain coronal sections of ethanol-treated mice. Mesenchymal stem cell\u2013derived 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\u2013derived extracellular vesicles revealed the elevated expression of extracellular vesicle\u2013derived miR-483-5p and miR-140-3p in the brains of ethanol-treated female mice following mesenchymal stem cell\u2013derived extracellular vesicle administration. In addition, mesenchymal stem cell\u2013derived extracellular vesicles modulated the expression of pro-inflammatory-related miRNA target genes (e.g.,\n                    <jats:italic toggle=\"yes\">Socs3<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Tnf<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Mtor<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Atf6<\/jats:italic>\n                    ) in the brains of ethanol-treated female mice. These results suggest that mesenchymal stem cell\u2013derived 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.\n                  <\/jats:p>","DOI":"10.4103\/nrr.nrr-d-24-01260","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T21:00:07Z","timestamp":1750366807000},"page":"2370-2379","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Role of miRNAs from mesenchymal stem cell\u2013derived extracellular vesicles in neuroinflammation and behavioral impairments induced by chronic alcohol consumption in female mice"],"prefix":"10.4103","volume":"21","author":[{"given":"Susana","family":"Mellado","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine and Dentistry, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najoua","family":"Touahri","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine and Dentistry, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Montagud-Romero","sequence":"additional","affiliation":[{"name":"Department of Psychobiology, School of Psychology, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Perpi\u00f1\u00e1-Cl\u00e9rigues","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine and Dentistry, University of Valencia, Valencia, Spain"},{"name":"Computational Biomedicine Laboratory, Pr\u00edncipe Felipe Research Center, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Computational Biomedicine Laboratory, Pr\u00edncipe Felipe Research Center, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Moreno-Manzano","sequence":"additional","affiliation":[{"name":"Neuronal and Tissue Regeneration Laboratory, Pr\u00edncipe Felipe Research Center, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Guerri","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine and Dentistry, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Rodr\u00edguez-Arias","sequence":"additional","affiliation":[{"name":"Department of Psychobiology, School of Psychology, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-631X","authenticated-orcid":false,"given":"Mar\u00eda","family":"Pascual","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine and Dentistry, University of Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"R1-20260416","doi-asserted-by":"crossref","first-page":"8285","DOI":"10.1523\/JNEUROSCI.0976-10.2010","article-title":"Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage","volume":"30","author":"Alfonso-Loeches","year":"2010","journal-title":"J Neurosci"},{"key":"R2-20260416","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.tox.2013.03.001","article-title":"Gender differences in alcohol-induced neurotoxicity and brain 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