{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:10:32Z","timestamp":1773097832077,"version":"3.50.1"},"reference-count":134,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Speed, crash and run: exersomes boost neuroenergetics and mood in mice on speed project","award":["POCI-01-0145-FEDER-030786; PTDC\/SAU-DES\/30786\/2017"],"award-info":[{"award-number":["POCI-01-0145-FEDER-030786; PTDC\/SAU-DES\/30786\/2017"]}]},{"name":"Strategic Projects","award":["UID\/NEU\/04539\/2013 and UID\/NEU\/ 04539\/2019"],"award-info":[{"award-number":["UID\/NEU\/04539\/2013 and UID\/NEU\/ 04539\/2019"]}]},{"name":"COMPETE-FEDER","award":["POCI-01-0145-FEDER-007440"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440"]}]},{"name":"Centro 2020 Regional Operational Programmes","award":["CENTRO-01-0145-FEDER-000012: HealthyAging2020 and CENTRO-01-0145-FEDER- 000008: BrainHealth 2020"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-000012: HealthyAging2020 and CENTRO-01-0145-FEDER- 000008: BrainHealth 2020"]}]},{"name":"Strategic Project","award":["UIDB\/04539\/2020 and UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020 and UIDP\/04539\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: One mechanism through which physical activity (PA) provides benefits is by triggering activity at a molecular level, where neurotrophins (NTs) are known to play an important role. However, the expression of the circulating levels of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4\/5), in response to exercise, is not fully understood. Therefore, the aim was to provide an updated overview on the neurotrophin (NT) variation levels of BDNF and NT-4\/5 as a consequence of a long-term aerobic exercise intervention, and to understand and describe whether the upregulation of circulating NT levels is a result of neurotrophic factors produced and released from the brain, and\/or from neurotrophic secreting peripheral organs. (2) Methods: The articles were collected from PubMed, SPORTDiscus, Web of Science, MEDLINE, and Embase. Data were analyzed through a narrative synthesis. (3) Results: 30 articles studied humans who performed training protocols that ranged from 4 to 48 weeks; 22 articles studied rodents with an intervention period that ranged from 4 to 64 weeks. (4) Conclusions: There is no unanimity between the upregulation of BDNF in humans; conversely, concerning both BDNF and NT-4\/5 in animal models, the results are heterogeneous. Whilst BDNF upregulation appears to be in relative agreement, NT-4\/5 seems to display contradictory and inconsistent conclusions.<\/jats:p>","DOI":"10.3390\/ijms22168814","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T21:27:45Z","timestamp":1629149265000},"page":"8814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["The Impact of Physical Exercise on the Circulating Levels of BDNF and NT 4\/5: A Review"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8547-6443","authenticated-orcid":false,"given":"Daniel","family":"Ribeiro","sequence":"first","affiliation":[{"name":"University of Coimbra, Faculty of Sport Sciences and Physical Education, Coimbra Institute for Clinical and Biomedical Research, 3004-504 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, 3004-504 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research, 3004-504 Coimbra, Portugal"}]},{"given":"Luca","family":"Petrigna","sequence":"additional","affiliation":[{"name":"Sport and Exercise Sciences Research Unit, Department of Psychology, Educational Science and Human Movement, University of Palermo, 90144 Palermo, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9381-3320","authenticated-orcid":false,"given":"Frederico C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"University of Coimbra, Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, 3004-504 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research, 3004-504 Coimbra, Portugal"},{"name":"University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-9929","authenticated-orcid":false,"given":"Antonella","family":"Muscella","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Science and Technologies (DiSTeBA), University of Salento, 73100 Lecce, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-6581","authenticated-orcid":false,"given":"Antonino","family":"Bianco","sequence":"additional","affiliation":[{"name":"Sport and Exercise Sciences Research Unit, Department of Psychology, Educational Science and Human Movement, University of Palermo, 90144 Palermo, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2287-2446","authenticated-orcid":false,"given":"Paula","family":"Tavares","sequence":"additional","affiliation":[{"name":"University of Coimbra, Faculty of Sport Sciences and Physical Education, Coimbra Institute for Clinical and Biomedical Research, 3004-504 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Institute of Pharmacology and Experimental Therapeutics, 3004-504 Coimbra, Portugal"},{"name":"University of Coimbra, Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research, 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/oby.2006.46","article-title":"Neurobiology of exercise","volume":"14","author":"Dishman","year":"2006","journal-title":"Obesity (Silver Spring)"},{"key":"ref_2","first-page":"533","article-title":"The effect of physical activity on the brain derived neurotrophic factor: From animal to human studies","volume":"61","author":"Zoladz","year":"2010","journal-title":"J. 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