{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:07:14Z","timestamp":1789682834461,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T00:00:00Z","timestamp":1744502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"Abstract<\/jats:title>Brain\u2010derived neurotrophic factor (BDNF) is essential for neuroplasticity. Exercise can induce increases in forearm venous plasma and serum BDNF, often assumed to be indicative of release from the brain. We investigated the effects of exercise on circulating levels of mature BDNF (mBDNF) and its precursor proBDNF. Sixteen healthy, physically fit adults (20\u201340\u00a0years old) cycled for 20\u00a0min at 40, 60 and 80% of , separated by 30\u00a0min of rest. BDNF was analysed in blood samples from the brachial artery, internal jugular vein, femoral vein and antecubital vein. Brain\/skeletal muscle exchange of BDNF, calculated as arterial\u2013venous differences in BDNF multiplied by blood flow in the middle cerebral artery\/common femoral artery, was measured simultaneously with blood sampling. Exercise intensity\u2010dependent increases were observed in blood platelet count, forearm venous serum mBDNF and plasma proBDNF, but not in forearm venous plasma mBDNF. Brain release (or uptake) was not detected for either plasma mBDNF, serum mBDNF or plasma proBDNF. However, muscle uptake of plasma mBDNF and release of plasma proBDNF were observed after high\u2010intensity exercise. Our findings demonstrate that exercise\u2010dependent increases in serum mBDNF are not derived from the brain or the exercised skeletal muscle. Rather, the source of the increase appears to be the increase in platelets that are enriched with mBDNF. Furthermore, in physically fit adults, BDNF is not released from the brain into the bloodstream, after exercise, regardless of exercise intensity. Finally, changes in plasma proBDNF after exercise appear to be dependent on exercised skeletal muscle rather than brain release.\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>Key points<\/jats:title>\nPreviously shown exercise\u2010induced increases in forearm venous brain\u2010derived neurotrophic factor (BDNF) are often assumed to be indicative of release from the brain.<\/jats:p><\/jats:list-item>\nWe investigated whether exercise\u2010induced changes in forearm venous mature BDNF (mBDNF) and precursor proBDNF are paralleled by concomitant changes in BDNF exchange over the brain and skeletal muscle.<\/jats:p><\/jats:list-item>\nWe observed exercise intensity\u2010dependent increases in platelet count, forearm venous serum mBDNF and plasma proBDNF, but not in forearm venous plasma mBDNF.<\/jats:p><\/jats:list-item>\nWe found muscle uptake of plasma mBDNF and release of plasma proBDNF after high\u2010intensity exercise but no exercise intensity\u2010dependent brain exchange of either plasma mBDNF, serum mBDNF or plasma proBDNF.<\/jats:p><\/jats:list-item>\nOur findings suggest that acute exercise\u2010induced increases in circulating serum mBDNF may be solely a result of increased platelet count, probably due to splenic platelet release; and that exercised skeletal muscle, and not the brain, responds to high\u2010intensity exercise by releasing plasma proBDNF.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp288409","type":"journal-article","created":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T08:44:16Z","timestamp":1744533856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Arterial\u2013venous differences of brain\u2010derived neurotrophic factor isoforms across the brain and muscle after exercise at different intensities"],"prefix":"10.1113","author":[{"given":"Olga","family":"Tarassova","sequence":"first","affiliation":[{"name":"Department of Physical Activity and Health The Swedish School of Sport and Health Sciences (GIH) Stockholm Sweden"},{"name":"Department of Physiology, Nutrition, and Biomechanics The Swedish School of Sport and Health Sciences (GIH) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Physical Activity and Health The Swedish School of Sport and Health Sciences (GIH) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9187-2426","authenticated-orcid":false,"given":"Helena","family":"Wallin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Division of Clinical Physiology Karolinska Institutet Stockholm Sweden"},{"name":"Department of Clinical Physiology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Jensen\u2010Urstad","sequence":"additional","affiliation":[{"name":"Department of Cardiology Karolinska University Hospital and Heart and Lung Disease Unit, Department of Medicine, Huddinge, Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9158-4942","authenticated-orcid":false,"given":"Nikola","family":"Drca","sequence":"additional","affiliation":[{"name":"Department of Cardiology Karolinska University Hospital and Heart and Lung Disease Unit, Department of Medicine, Huddinge, Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"R\u00f6ja","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nutrition, and Biomechanics The Swedish School of Sport and Health Sciences (GIH) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Pont\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nutrition, and Biomechanics The Swedish School of Sport and Health Sciences (GIH) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3402-9891","authenticated-orcid":false,"given":"Abram","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nutrition, and Biomechanics The Swedish School of Sport and Health Sciences (GIH) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonna","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Physical Activity and Health The Swedish School of Sport and Health Sciences (GIH) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Ekblom","sequence":"additional","affiliation":[{"name":"Department of Physical Activity and Health The Swedish School of Sport and Health Sciences (GIH) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3747-0148","authenticated-orcid":false,"given":"Marcus","family":"Moberg","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nutrition, and Biomechanics The Swedish School of Sport and Health Sciences (GIH) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,13]]},"reference":[{"issue":"6","key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3171\/jns.1982.57.6.0769","article-title":"Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries","volume":"57","author":"Aaslid R.","year":"1982","journal-title":"Journal of Neurosurgery"},{"issue":"9","key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1139\/apnm-2021-0220","article-title":"Protocol\u2010dependence of middle cerebral artery dilation to modest hypercapnia","volume":"46","author":"Al\u2010Khazraji B. 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