{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:55:14Z","timestamp":1790258114307,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006221","name":"United States - Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["2054\/18"],"award-info":[{"award-number":["2054\/18"]}],"id":[{"id":"10.13039\/100006221","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Many nutrients essential to the fetus and for proper function of the placenta itself cannot freely diffuse across membrane barriers, and their transplacental transfer depends on transporters. Our previous studies provided evidence for altered expression of transporters for folic acid in trophoblasts exposed to antiseizure medications (ASMs). The goal of the current study was to explore the effects of older and newer ASMs on the expression and function of uptake transporters for choline, which interacts with folate at pathways for methyl group donation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BeWo cells were incubated for 2 or 5\u00a0days with valproate (42, 83, or 166\u00a0\u00b5g\/ml), carbamazepine (6 or 12\u00a0\u00b5g\/ml), levetiracetam (10 or 30\u00a0\u00b5g\/ml), lamotrigine (3 or 12\u00a0\u00b5g\/ml), lacosamide (5, 10, or 20\u00a0\u00b5g\/ml), or their vehicles (<jats:italic>n<\/jats:italic>\u00a0=\u00a06\/treatment group). Quantitative polymerase chain reaction (PCR) analysis was utilized to study the effects of ASMs on the transcript levels of the choline transporters<jats:italic>SLC44A1<\/jats:italic>(CTL1) and<jats:italic>SLC44A2<\/jats:italic>(CTL2). Transporter protein expression in valproate\u2010treated cells was assessed by western blot analysis. Choline and acetylcholine were quantified in cell lysates by a choline\/acetylcholine assay kit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with controls, valproate and levetiracetam at high therapeutic concentrations (83 and 30\u00a0\u00b5g\/ml, respectively) lowered choline transporter transcript levels by up to 42% and 26%, and total choline levels by 20% and 21%, respectively (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05). At 83\u00a0\u03bcg\/ml, valproate additionally reduced CTL1 and CTL2 protein expression, by 39\u00a0\u00b1\u00a021% and 61\u00a0\u00b1\u00a013% (mean \u00b1 SD), respectively (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01). Carbamazepine reduced<jats:italic>SLC44A1<\/jats:italic>transcript levels, whereas lacosamide modestly decreased the expression of<jats:italic>SLC44A2<\/jats:italic>. Lamotrigine did not alter choline transporter expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Antiseizure medications, particularly at high therapeutic concentrations, can interfere with the placental uptake of choline. In line with current knowledge from pregnancy registries and clinical studies, the present in vitro findings further support careful adjustment of maternal ASM doses during pregnancy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16905","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T06:00:45Z","timestamp":1619157645000},"page":"1451-1459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Antiseizure medications and fetal nutrients: Effects on choline transporters in a human placental cell line"],"prefix":"10.1111","volume":"62","author":[{"given":"Nino","family":"Tetro","sequence":"first","affiliation":[{"name":"School of Pharmacy Institute for Drug Research The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Moushaev","sequence":"additional","affiliation":[{"name":"School of Pharmacy Institute for 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