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Using the neuron-specific protein SNAP25, we investigated the cargo of neuron-derived extracellular vesicles (NEVs) isolated from plasma in relation to antidepressant treatment and identified miR-151a-5p as a mediator of treatment response, increasing selectively in responders while remaining low in non-responders. Plasma levels mirrored deficits in human post-mortem brain tissue from the ventral anterior cingulate cortex, a cortical area implicated in MDD. In mice, engineered NEVs enriched with miR-151a-5p delivered cargo selectively to neurons, where miR-151a-5p engaged the RNA-induced silencing complex and regulated genes involved in synaptic networks, including RIMS3 and ELAVL3. Moreover, administration of miR-151a-5p\u2013loaded NEVs in a model of depressive-like behavior produced rapid antidepressant-like effects. Together, these findings identify a vesicle-based mechanism linking peripheral biomarkers to central pathophysiology and demonstrate that miR-151a-5p functions both as a predictor and effector of antidepressant response.<\/jats:p>","DOI":"10.64898\/2026.08.11.26360193","type":"posted-content","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T22:15:12Z","timestamp":1786572912000},"source":"Crossref","is-referenced-by-count":0,"title":["miR-151a-5p in Neuron-Derived Extracellular Vesicles Mediates Antidepressant Response"],"prefix":"10.64898","author":[{"given":"Dariusz","family":"\u017burawek","sequence":"first","affiliation":[{"name":"McGill Group for Suicide Studies, Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Canada"},{"name":"Department of General Biochemistry, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 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