{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:08:40Z","timestamp":1790744920632,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,6,15]],"date-time":"2016-06-15T00:00:00Z","timestamp":1465948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002736","name":"Citizens United for Research in Epilepsy","doi-asserted-by":"publisher","award":["R03NS078591"],"award-info":[{"award-number":["R03NS078591"]}],"id":[{"id":"10.13039\/100002736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002736","name":"Citizens United for Research in Epilepsy","doi-asserted-by":"publisher","award":["R01HL117871"],"award-info":[{"award-number":["R01HL117871"]}],"id":[{"id":"10.13039\/100002736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201506370075"],"award-info":[{"award-number":["201506370075"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006765","name":"Chinese Medical Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006765","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The DBA\/1 mouse is a relevant animal model of sudden unexpected death in epilepsy (SUDEP), as it exhibits seizure\u2010induced respiratory arrest (S\u2010IRA) evoked by acoustic stimulation, followed by cardiac arrhythmia and death. Defects in serotonergic neurotransmission may contribute to S\u2010IRA. The tryptophan hydroxylase\u20102 (TPH2) enzyme converts L\u2010tryptophan to 5\u2010hydroxytryptophan (5\u2010HTP), a precursor for central nervous system (CNS) serotonin (5\u2010HT) synthesis; and DBA\/1 mice have a polymorphism that decreases TPH2 activity. We, therefore, hypothesized that supplementation with 5\u2010HTP may bypass TPH2 and suppress S\u2010IRA in DBA\/1 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TPH2 expression was examined by Western blot in the brainstem of DBA\/1 and C57BL\/6J mice both with and without acoustic stimulation. Changes in breathing and cardiac electrical activity in DBA\/1 and C57BL\/6J mice that incurred sudden death during generalized seizures evoked by pentylenetetrazole (PTZ) were studied by plethysmography and electrocardiography. The effect of 5\u2010HTP administration on seizure\u2010induced mortality evoked by acoustic stimulation or by PTZ was investigated in DBA\/1 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Repetitive acoustic stimulation resulted in reduced TPH2 protein in the brainstem of DBA\/1 mice as compared with C57BL\/6J mice. S\u2010IRA evoked by acoustic stimulation in DBA\/1 mice was significantly reduced by 5\u2010HTP. Following S\u2010IRA, cardiac electrical activity could be detected for minutes before terminal asystole and death in both DBA\/1 and C57BL\/6J mice after PTZ treatment. The incidence of S\u2010IRA by PTZ administration was greater in DBA\/1 than in C57BL\/6J mice, and administration of 5\u2010HTP also significantly reduced S\u2010IRA by PTZ in DBA\/1 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Our data suggest that S\u2010IRA is the primary event leading to death incurred in most DBA\/1 and some C57BL\/6J mice during PTZ\u2010evoked seizures. Suppression of S\u2010IRA by 5\u2010HTP suggests that 5\u2010HT transmission contributes to the pathophysiology of S\u2010IRA, and that 5\u2010HTP, an over\u2010the\u2010counter supplement available for human consumption, may be clinically useful in preventing SUDEP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.13430","type":"journal-article","created":{"date-parts":[[2016,6,15]],"date-time":"2016-06-15T11:19:19Z","timestamp":1465989559000},"page":"1228-1235","source":"Crossref","is-referenced-by-count":55,"title":["5\u2010Hydroxytryptophan, a precursor for serotonin synthesis, reduces seizure\u2010induced respiratory arrest"],"prefix":"10.1111","volume":"57","author":[{"given":"Honghai","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesia Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School Boston Massachusetts U.S.A."},{"name":"Department of Anesthesia Hangzhou First People's Hospital Nanjing Medical University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School Boston Massachusetts U.S.A."},{"name":"Department of Neurology The First Affiliated Hospital of Xiamen University Xiamen China"},{"name":"Department of Neurology Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School Boston Massachusetts U.S.A."},{"name":"Department of Anesthesiology Ruijin Hospital School of Medicine Shanghai Jiaotong University Shanghai 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