Antiseizure medications and fetal nutrients: Effects on choline transporters in a human placental cell line

Objective 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 tr...

Full description

Saved in:
Bibliographic Details
Published in:Epilepsia (Copenhagen) 2021-06, Vol.62 (6), p.1451-1459
Main Authors: Tetro, Nino, Moushaev, Sonia, Shmuel, Miri, Eyal, Sara
Format: Article
Language:English
Subjects:
Acetylcholine
antiepileptic drugs
Carbamazepine
Choline
Etiracetam
Fetuses
Folic acid
Lamotrigine
Lysates
neurodevelopment
Nutrients
Placenta
Polymerase chain reaction
Pregnancy
Protein expression
Protein transport
Transcription
Trophoblasts
Valproic acid
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objective 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. Methods BeWo cells were incubated for 2 or 5 days with valproate (42, 83, or 166 µg/ml), carbamazepine (6 or 12 µg/ml), levetiracetam (10 or 30 µg/ml), lamotrigine (3 or 12 µg/ml), lacosamide (5, 10, or 20 µg/ml), or their vehicles (n = 6/treatment group). Quantitative polymerase chain reaction (PCR) analysis was utilized to study the effects of ASMs on the transcript levels of the choline transporters SLC44A1 (CTL1) and SLC44A2 (CTL2). Transporter protein expression in valproate‐treated cells was assessed by western blot analysis. Choline and acetylcholine were quantified in cell lysates by a choline/acetylcholine assay kit. Results Compared with controls, valproate and levetiracetam at high therapeutic concentrations (83 and 30 µg/ml, respectively) lowered choline transporter transcript levels by up to 42% and 26%, and total choline levels by 20% and 21%, respectively (p 
ISSN:0013-9580
1528-1167
DOI:10.1111/epi.16905