{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:28:46Z","timestamp":1777858126431,"version":"3.51.4"},"reference-count":82,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2013,10,9]],"date-time":"2013-10-09T00:00:00Z","timestamp":1381276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>Electroconvulsive therapy is an important treatment option for major depressive disorders, acute mania, mood disorders with psychotic features, and catatonia. Several hypotheses have been proposed as electroconvulsive therapy\u2019s mechanism of action. Our hypothesis involves many converging pathways facilitated by increased synthesis and release of tissue-plasminogen activator.<\/jats:p>\n                  <jats:p>Human and animal experiments have shown that tissue-plasminogen activator participates in many mechanisms of action of electroconvulsive therapy or its animal variant, electroconvulsive stimulus, including improved N-methyl-D-aspartate receptor-mediated signaling, activation of both brain-derived neurotrophic factor and vascular endothelial growth factor, increased bioavailability of zinc, purinergic release, and increased mobility of dendritic spines. As a result, tissue-plasminogen activator helps promote neurogenesis in limbic structures, modulates synaptic transmission and plasticity, improves cognitive function, and mediates antidepressant effects.<\/jats:p>\n                  <jats:p>Notably, electroconvulsive therapy seems to influence tissue-plasminogen activator metabolism. For example, electroconvulsive stimulus increases the expression of glutamate decarboxylase 65 isoform in \u03b3-aminobutyric acid\u2013releasing neurons, which enhances the release of tissue-plasminogen activator, and the expression of p11, a protein involved in plasminogen and tissue-plasminogen activator assembling.<\/jats:p>\n                  <jats:p>This paper reviews how electroconvulsive therapy correlates with tissue-plasminogen activator. We suggest that interventions aiming at increasing tissue-plasminogen activator levels or its bioavailability \u2013 such as daily aerobic exercises together with a carbohydrate-restricted diet, or normalization of homocysteine levels \u2013 be evaluated in controlled studies assessing response and remission duration in patients who undergo electroconvulsive therapy.<\/jats:p>","DOI":"10.1177\/0269881113507639","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T12:29:35Z","timestamp":1381494575000},"page":"99-105","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy"],"prefix":"10.1177","volume":"28","author":[{"given":"Silvia","family":"Hoirisch-Clapauch","sequence":"first","affiliation":[{"name":"Department of Hematology, Hospital Federal dos Servidores do Estado, Ministry of Health, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco AU","family":"Mezzasalma","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry. Federal University of Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio E","family":"Nardi","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry. 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