| Short-term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T. | |
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MedLine Citation:
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PMID: 21176029 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Altered metabolism of membrane phospholipids has been implicated in bipolar disorder. In humans, uridine is an important precursor of cytidine diphosphate (CDP)-choline, which plays a critical role in phospholipid synthesis and is currently being evaluated as a potential treatment for bipolar depression. METHODS: A total of 17 healthy males (mean age ± SD: 32.73 ± 7.2 years; range: 21.8-46.4 years) were enrolled in this study. Subjects underwent a 31-phosphorus magnetic resonance spectroscopy ((31) P-MRS) acquisition at baseline and then again after seven days of either 2 g of uridine or placebo administration. A two-dimensional chemical shift imaging (31) P-MRS acquisition collected spectral data from a 4 × 4 cluster of voxels acquired in the axial plane encompassing the subcortical structures as well as frontal-temporal cortical gray and white matter. The slab thickness was 3 cm and the approximate total volume of brain sampled was 432 cm(3) . The spectra obtained were analyzed using a fully automated in-house fitting algorithm. A population-averaged generalized estimating equation was used to evaluate changes both in phosphomonoesters (PME) [phosphocholine (PCho) and phosphoethanolamine (PEtn)] and phosphodiesters (PDE) [glycerophosphocholine (GPCho) and glycerophosphethanolamine (GPEtn)]. Metabolite ratios were reported with respect to the total integrated (31) P resonance area. RESULTS: The uridine group had significantly increased total PME and PEtn levels over the one-week period [6.32 and 7.17% for PME and PEtn, respectively (p<0.001)]. Other metabolite levels such as PCho, PDE, GPEtn and GPCho showed no significant changes following either uridine or placebo (all p>0.05). CONCLUSIONS: This is the first study to report a direct effect of uridine on membrane phospholipid precursors in healthy adults using (31) P-MRS. Sustained administration of uridine appears to increase PME in healthy subjects. Further investigation is required to clarify the effects of uridine in disorders with altered phospholipid metabolism such as bipolar disorder. |
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Authors:
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Nivedita Agarwal; Young-Hoon Sung; J Eric Jensen; Grace daCunha; David Harper; David Olson; Perry F Renshaw |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Bipolar disorders Volume: 12 ISSN: 1399-5618 ISO Abbreviation: Bipolar Disord Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-23 Completed Date: 2011-08-10 Revised Date: 2012-03-15 |
Medline Journal Info:
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Nlm Unique ID: 100883596 Medline TA: Bipolar Disord Country: Denmark |
Other Details:
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Languages: eng Pagination: 825-33 Citation Subset: IM |
Copyright Information:
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© 2010 John Wiley and Sons A/S. |
Affiliation:
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The Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City, UT 84102, USA. niv_aga@yahoo.co.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Brain / drug effects*, metabolism Cytidine Diphosphate Choline / pharmacology* Ethanolamines / metabolism Female Humans Magnetic Resonance Spectroscopy Male Middle Aged Phosphatidylethanolamines / metabolism Phospholipids / metabolism* Phosphorus Isotopes Phosphorylcholine / metabolism Time Factors Uridine / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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K05 DA031247-02/DA/NIDA NIH HHS; MH58681/MH/NIMH NIH HHS; R01 MH058681-02/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ethanolamines; 0/Phosphatidylethanolamines; 0/Phospholipids; 0/Phosphorus Isotopes; 107-73-3/Phosphorylcholine; 1071-23-4/phosphorylethanolamine; 1190-00-7/glycerophosphoethanolamine; 58-96-8/Uridine; 987-78-0/Cytidine Diphosphate Choline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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