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. 2023 Jun 15;10:1154872. doi: 10.3389/fmolb.2023.1154872

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Copyright © 2023 Khoury and Nagy.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Aerobic exercise causes skeletal muscles to release exercise-induced sEVs into blood circulation. These sEVs contain important exerkines (cytokines, microRNAs) and are taken up by other tissues such as the brain. Exercise-induced sEVs cross the BBB via different putative mechanisms (transcytosis, micropinocytosis, and clathrin-dependent endocytosis), and influence neural pathways associated with the etiopathogenesis of major depression, such as neurogenesis, neural plasticity and neuroinflammation, hence mediating the beneficial effects of exercise on MDD.