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Maternal choline supplementation programs offspring choline metabolism in a mouse model of Down syndrome
Author(s) -
Yan Jian,
Ginsberg Stephen D,
Powers Brian,
Alldred Melissa J,
Saltzman Arthur,
Strupp Barbara J,
Caudill Marie A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.111.5
Subject(s) - choline , offspring , endocrinology , medicine , phosphatidylcholine , neocortex , weaning , phosphorylcholine , biology , pregnancy , phospholipid , biochemistry , neuroscience , membrane , genetics
Maternal choline supplementation (MCS) induces lifelong cognitive benefits in the Ts65Dn mouse, a model of Down syndrome and Alzheimer's disease. To gain insight into the mechanism(s) underlying these beneficial effects, we conducted a study to test the hypothesis that MCS alters brain choline metabolism in adult Ts65Dn offspring. Ts65Dn dams were randomly assigned to a control diet or one supplemented with additional choline (1.1 g/kg or 5.0 g/kg choline chloride) throughout pregnancy and lactation. After weaning, the offspring consumed standard rodent chow. At ~6–7 mo of age, deuterium labeled methyl ‐d9‐choline (1.6 mM) was administered as a tracer for 8 wks in the drinking water of the female offspring (Ts65Dn and disomic littermates) and brain tissues were harvested. Choline‐supplemented Ts65Dn mice had higher ( P < 0.05) enrichment of all examined choline metabolites (e.g., d9‐acetylcholine) and a higher ( P < 0.05) enrichment ratio of d3‐choline/d3‐glycerophosphocholine (GPC), d3‐GPC/d3‐phosphatidylcholine (PtdCho), and d3‐choline/d3‐PtdCho in the basal forebrain, hippocampus, and neocortex compared to unsupplemented Ts65Dn mice. No effect of MCS was detected in normal disomic littermates. These data suggest that MCS produces lifelong changes in choline metabolism in female Ts65Dn offspring with evidence of enhanced uptake and use of choline (and its methyl groups) in several brain regions. Funded by HD057564 , AG14449, and the Alzheimer's Association