{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:18:24Z","timestamp":1790551104489,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T00:00:00Z","timestamp":1561334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006117","name":"Epilepsiefonds","doi-asserted-by":"publisher","award":["16-09"],"award-info":[{"award-number":["16-09"]}],"id":[{"id":"10.13039\/501100006117","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000311","name":"Tuberous Sclerosis Association","doi-asserted-by":"publisher","award":["2014-F02"],"award-info":[{"award-number":["2014-F02"]}],"id":[{"id":"10.13039\/501100000311","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>An epilepsy mouse model for Tuberous Sclerosis Complex (TSC) was developed and validated to investigate the mechanisms underlying epileptogenesis. Furthermore, the possible antiepileptogenic properties of commonly used antiepileptic drugs (AEDs) and new compounds were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Tsc1<\/jats:italic> deletion was induced in CAMK2A\u2010expressing neurons of adult mice. The antiepileptogenic properties of commonly used AEDs and inhibitors of the mTOR pathways were assessed by EEG recordings and by molecular read outs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice developed epilepsy in a narrow time window (10\u00a0\u00b1\u00a02\u00a0days) upon <jats:italic>Tsc1<\/jats:italic> gene deletion. Seizure frequency but not duration increased over time. Seizures were lethal within 18\u00a0days, were unpredictable, and did not correlate to seizure onset, length or frequency, reminiscent of sudden unexpected death in epilepsy (SUDEP). <jats:italic>Tsc1<\/jats:italic> gene deletion resulted in a strong activation of the mTORC1 pathway, and both epileptogenesis and lethality could be entirely prevented by <jats:italic>RHEB1<\/jats:italic> gene deletion or rapamycin treatment. However, other inhibitors of the mTOR pathway such as AZD8055 and PF4708671 were ineffective. Except for ketogenic diet, none of commonly used AEDs showed an effect on mTORC1 activity. Vigabatrin and ketogenic diet treatment were able to significantly delay seizure onset. In contrast, survival was shortened by lamotrigine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This novel <jats:italic>Tsc1<\/jats:italic> mouse model is highly suitable to assess the efficacy of antiepileptic and \u2010epileptogenic drugs to treat mTORC1\u2010dependent epilepsy. Additionally, it allows us to study the mechanisms underlying mTORC1\u2010mediated epileptogenesis and SUDEP. We found that early treatment with vigabatrin was not able to prevent epilepsy, but significantly delayed seizure onset.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50829","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T18:47:24Z","timestamp":1561488444000},"page":"1273-1291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Effects of antiepileptic drugs in a new TSC\/mTOR\u2010dependent epilepsy mouse model"],"prefix":"10.1002","volume":"6","author":[{"given":"Linda M. 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