title: Maternal choline supplementation programs greater activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway in adult Ts65Dn trisomic mice.
abstract: Maternal choline supplementation (MCS) induces lifelong cognitive benefits in the Ts65Dn mouse, a trisomic mouse model of Down syndrome and Alzheimer's disease. To gain insight into the mechanisms underlying these beneficial effects, we conducted a study to test the hypothesis that MCS alters choline metabolism in adult Ts65Dn offspring. Deuterium-labeled methyl-d9-choline was administered to adult Ts65Dn and disomic (2N) female littermates born to choline-unsupplemented or choline-supplemented Ts65Dn dams. Enrichment of d9-choline metabolites (derived from intact choline) and d3 + d6-choline metabolites [produced when choline-derived methyl groups are used by phosphatidylethanolamine N-methyltransferase (PEMT)] was measured in harvested tissues. Adult offspring (both Ts65Dn and 2N) of choline-supplemented (vs. choline-unsupplemented) dams exhibited 60% greater (P≤0.007) activity of hepatic PEMT, which functions in de novo choline synthesis and produces phosphatidylcholine (PC) enriched in docosahexaenoic acid. Higher (P<0.001) enrichment of PEMT-derived d3 and d6 metabolites was detected in liver, plasma, and brain in both genotypes but to a greater extent in the Ts65Dn adult offspring. MCS also yielded higher (P<0.05) d9 metabolite enrichments in liver, plasma, and brain. These data demonstrate that MCS exerts lasting effects on offspring choline metabolism, including up-regulation of the hepatic PEMT pathway and enhanced provision of choline and PEMT-PC to the brain.
authors: Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA;
authors: Jian
authors: J
authors: Yan
authors: Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, USA; and Department of Psychiatry and Department of Physiology and Neuroscience, New York University Langone Medical Center, New York, New York, USA.
authors: Stephen D
authors: SD
authors: Ginsberg
authors: Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA;
authors: Brian
authors: B
authors: Powers
authors: Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, USA; and Department of Psychiatry and.
authors: Melissa J
authors: MJ
authors: Alldred
authors: Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York, USA; and.
authors: Arthur
authors: A
authors: Saltzman
authors: Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA;
authors: Barbara J
authors: BJ
authors: Strupp
authors: Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA; mac379@cornell.edu.
authors: Marie A
authors: MA
authors: Caudill
mesh_terms: D000818:Animals; D002794:Choline / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004314:Down Syndrome / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014018:Tissue Distribution
chemical_list: D010713:Phosphatidylcholines; D004281:Docosahexaenoic Acids; C559160:PEMT protein, mouse; D050918:Phosphatidylethanolamine N-Methyltransferase; D002794:Choline
keywords: Alzheimer's disease; Down syndrome; docosahexaenoic acid; fetal programming; phosphatidylcholine