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Table · dataset · 2026

Data Sheet 1_Acute aerobic exercise is associated with a biphasic, temporally ordered shift in serum extracellular vesicle microRNA expression in major depressive disorder.pdf

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Introduction<p>Acute aerobic exercise (AAE) is known to reduce symptoms of Major Depressive Disorder (MDD), yet the underlying biological mechanisms remain poorly understood.

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Here, we profiled microRNA (miRNA) expression within the serum extracellular vesicle (EV) enriched fraction (hereafter 'EV-enriched miRNA') of individuals diagnosed with MDD at multiple timepoints: before, during (mid), immediately after, and 75 min following a single 30-min session of moderate aerobic exercise.

By characterizing the temporal dynamics of EV-enriched miRNA responses to AAE, our objective was to uncover molecular changes that may mediate exercise-induced molecular adaptations relevant to short- or long-term antidepressant effects of exercise and to identify candidate EV-enriched miRNAs for future mechanistic investigation of MDD.</p>Methods<p>An EV-enriched serum fraction was isolated from a minimum of 28 individuals diagnosed with MDD.

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MicroRNA profiles were then assessed via RNA deep sequencing and analyzed with using DESeq2.</p>Results<p>We identified time-dependent, significant (false discovery rate [FDR] ≤ 0.05) changes in EV-enriched microRNAs across AAE, with 15 differentially expressed at mid-AAE, 33 immediately post-AAE, and four at 75 min post-AAE. The response was biphasic and directional: miRNAs were predominantly downregulated during and immediately after exercise (13 of 15 down at mid-AAE; all 33 down post-AAE) and exclusively upregulated during recovery (all four up at 75 min post-AAE). hsa-miR-12523p was the only microRNA differentially expressed across all three postexercise timepoints, showing consistent downregulation.

Functional enrichment of predicted targets of significantly differentially expressed miRNAs revealed a temporally ordered shift from RNA processing and stability at mid-AAE, to dendrite, synapse, and axon organization immediately post-AAE, to synaptic transmission and neuronal development at 75 min post-AAE. </p>Discussion<p>AAE is associated with time-dependent, directional changes in EV-enriched microRNAs in MDD, whose predicted targets converge on synaptic plasticity pathways implicated in the disorder.

Together, this suggests microRNAs may contribute to the beneficial short- and potentially long-term effects of aerobic exercise in individuals with MDD and provides specific targets for future mechanistic investigation.</p>

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