{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:44:41Z","timestamp":1774982681272,"version":"3.50.1"},"reference-count":124,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T00:00:00Z","timestamp":1609977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-030786"],"award-info":[{"award-number":["POCI-01-0145-FEDER-030786"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/NEU\/04539\/2019"],"award-info":[{"award-number":["UID\/NEU\/04539\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014717","name":"Programa Operacional Regional do Centro","doi-asserted-by":"publisher","award":["CENTRO-01-0145-FEDER-000012: HealthyAging2020"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-000012: HealthyAging2020"]}],"id":[{"id":"10.13039\/501100014717","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014717","name":"Programa Operacional Regional do Centro","doi-asserted-by":"publisher","award":["CENTRO-01-0145-FEDER- 000008: BrainHealth 2020"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER- 000008: BrainHealth 2020"]}],"id":[{"id":"10.13039\/501100014717","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011929","name":"Programa Operacional Tem\u00e1tico Factores de Competitividade","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007440"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440"]}],"id":[{"id":"10.13039\/501100011929","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Depression is associated with an increased risk of aging-related diseases. It is also seemingly a common psychological reaction to pandemic outbreaks with forced quarantines and lockdowns. Thus, depression represents, now more than ever, a major global health burden with therapeutic management challenges. Clinical data highlights that physical exercise is gaining momentum as a non-pharmacological intervention in depressive disorders. Although it may contribute to the reduction of systemic inflammation associated with depression, the mechanisms underlying the beneficial physical exercise effects in emotional behavior remain to be elucidated. Current investigations indicate that a rapid release of extracellular vesicles into the circulation might be the signaling mediators of systemic adaptations to physical exercise. These biological entities are now well-established intercellular communicators, playing a major role in relevant physiological and pathophysiological functions, including brain cell\u2013cell communication. We also reviewed emerging evidence correlating depression with modified circulating extracellular vesicle surfaces and cargo signatures (e.g., microRNAs and proteins), envisioned as potential biomarkers for diagnosis, efficient disease stratification and appropriate therapeutic management. Accordingly, the clinical data summarized in the present review prompted us to hypothesize that physical exercise-related circulating extracellular vesicles contribute to its antidepressant effects, particularly through the modulation of inflammation. This review sheds light on the triad \u201cphysical exercise\u2013extracellular vesicles\u2013depression\u201d and suggests new avenues in this novel emerging field.<\/jats:p>","DOI":"10.3390\/ijms22020542","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T08:58:34Z","timestamp":1610096314000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Circulating Extracellular Vesicles: The Missing Link between Physical Exercise and Depression Management?"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2971-7788","authenticated-orcid":false,"given":"Edna","family":"Soares","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"}]},{"given":"Julie","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"}]},{"given":"Mariana","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9707-4895","authenticated-orcid":false,"given":"Carlos Fontes","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"}]},{"given":"Frederico C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"ref_1","unstructured":"WHO (2017). 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