title: Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally.
abstract: The synthesis of brain phosphatidylcholine may utilize three circulating precursors: choline; a pyrimidine (e.g., uridine, converted via UTP to brain CTP); and a PUFA (e.g., docosahexaenoic acid); phosphatidylethanolamine may utilize two of these, a pyrimidine and a PUFA. We observe that consuming these precursors can substantially increase membrane phosphatide and synaptic protein levels in gerbil brains. (Pyrimidine metabolism in gerbils, but not rats, resembles that in humans.) Animals received, daily for 4 weeks, a diet containing choline chloride and UMP (a uridine source) and/or DHA by gavage. Brain phosphatidylcholine rose by 13-22% with uridine and choline alone, or DHA alone, or by 45% with the combination, phosphatidylethanolamine and the other phosphatides increasing by 39-74%. Smaller elevations occurred after 1-3 weeks. The combination also increased the vesicular protein Synapsin-1 by 41%, the postsynaptic protein PSD-95 by 38% and the neurite neurofibrillar proteins NF-70 and NF-M by up to 102% and 48%, respectively. However, it had no effect on the cytoskeletal protein beta-tubulin. Hence, the quantity of synaptic membrane probably increased. The precursors act by enhancing the substrate saturation of enzymes that initiate their incorporation into phosphatidylcholine and phosphatidylethanolamine and by UTP-mediated activation of P2Y receptors. Alzheimer's disease brains contain fewer and smaller synapses and reduced levels of synaptic proteins, membrane phosphatides, choline and DHA. The three phosphatide precursors might thus be useful in treating this disease.
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar Street, 46-5023B MIT, Cambridge, MA 02139, USA. dick@mit.edu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wurtman
authors.forename: Ismail H
authors.initials: IH
authors.lastname: Ulus
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cansev
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Watkins
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: George
authors.initials: G
authors.lastname: Marzloff
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage; D004032:Diet; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects; D005849:Gerbillinae; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D013997:Time Factors; D014529:Uridine / Q000008:administration & dosage*
chemical_list: D009419:Nerve Tissue Proteins; D010743:Phospholipids; D016704:Synapsins; D004281:Docosahexaenoic Acids; D002794:Choline; D014529:Uridine