{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:51:39Z","timestamp":1790261499496,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,9,10]],"date-time":"2013-09-10T00:00:00Z","timestamp":1378771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Seizure development in tuberous sclerosis complex (TSC) correlates with the presence of specific lesions called cortical tubers. Moreover, heterozygous TSC animal models do not show gross brain pathology and are seizure\u2010free, suggesting that such pathology is a prerequisite for the development of epilepsy. However, cells within TSC lesions show increased activity of the target of rapamycin complex 1 (TORC1) pathway, and recent studies have implicated this pathway in non\u2013TSC\u2010related animal models of epilepsy and neuronal excitability. These findings imply a direct role for TORC1 in epilepsy. Here, we investigate the effect of increased TORC1 signaling induced by acute biallelic deletion of <jats:italic>Tsc1<\/jats:italic> in healthy adult mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Biallelic <jats:italic>Tsc1<\/jats:italic> gene deletion was induced in adult <jats:italic>Tsc1<\/jats:italic> heterozygous and wild\u2010type mice. Seizures were monitored by electroencephalographic and video recordings. Molecular and cellular changes were investigated by Western blot analysis, immunohistochemistry, and electrophysiology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice developed epilepsy a few days after biallelic <jats:italic>Tsc1<\/jats:italic> deletion. Acute gene deletion was not accompanied by any obvious histological changes, but resulted in activation of the TORC1 pathway, enhanced neuronal excitability, and a decreased threshold for protein\u2010synthesis\u2013dependent long\u2010term potentiation preceding the onset of seizures. Rapamycin treatment after seizure onset reduced TORC1 activity and fully abolished the seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our data indicate a direct role for TORC1 signaling in epilepsy development, even in the absence of major brain pathology. This suggests that TORC1 is a promising target for treating seizures not only in TSC but also in other forms of epilepsy that result from increased TORC1 activation. Ann Neurol 2013;74:569\u2013579<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.23943","type":"journal-article","created":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T08:22:53Z","timestamp":1369902173000},"page":"569-579","source":"Crossref","is-referenced-by-count":75,"title":["TORC1\u2010dependent epilepsy caused by acute biallelic <i>Tsc1<\/i> deletion in adult mice"],"prefix":"10.1002","volume":"74","author":[{"given":"Elisabeth","family":"Abs","sequence":"first","affiliation":[{"name":"Department of Neuroscience Erasmus University Medical Center Rotterdam the Netherlands"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders Erasmus University Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna M. I.","family":"Goorden","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus University Medical Center Rotterdam the Netherlands"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders Erasmus University Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadwiga","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus University Medical Center Rotterdam the Netherlands"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders Erasmus University Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris E.","family":"Overwater","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus University Medical Center Rotterdam the Netherlands"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders Erasmus University Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Hoogeveen\u2010Westerveld","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus University Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline F.","family":"Bruinsma","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus University Medical Center Rotterdam the Netherlands"},{"name":"ENCORE Expertise Center for Neurodevelopmental Disorders Erasmus University Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvedin","family":"Aganovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus University Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils 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