Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study

被引:37
作者
Babb, SM
Wald, LL
Cohen, BM
Villafuerte, RA
Gruber, SA
Yurgelun-Todd, DA
Renshaw, PF
机构
[1] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA
[2] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA
[3] Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA
关键词
5 '-cytidine diphosphate choline; choline; phosphatidylcholine; aging; brain; magnetic resonance spectroscopy;
D O I
10.1007/s00213-002-1045-y
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rationale: Phosphatidylcholine (PtdCho) in brain cell membranes decreases with age. Evidence from both animal and in vitro studies indicates that CDP-choline (citicoline) administration may increase phosphatidylcholine (PtdCho) synthesis and might reverse PtdCho loss. Objectives: We investigated whether oral citicoline can increase PtdCho synthesis in the brains of older subjects by measuring levels of phosphorus-containing metabolites using proton-decoupled phosphorus magnetic resonance spectroscopy (P-31-MRS) before and after citicoline treatment. Methods: All subjects took 500 mg citicoline once orally each day for 6 weeks, then took either citicoline or placebo once orally per day for a second 6-week period. Subjects underwent a 31P-MRS scan at baseline and following 6 and 12 weeks of treatment. Results: Treatment with citicoline for 6 weeks was associated with a 7.3% increase from baseline levels in brain phosphodiesters (P=0.008), including an 11.6% increase in glycerophosphoethanolamine (P=0.002) and a 5.1% increase in glycerophosphocholine (P=0.137). Subjects who continued to take citicoline for the second 6-week period did not show significant additional increases in the levels of these metabolites. No changes were seen in other phosphorus-containing metabolites. There was a correlation between improvement on the California Verbal Learning Test and increase in phosphodiesters. Conclusions: The increases in phosphodiesters seen in this study indicate that phospholipid synthesis and turnover were stimulated by 6 weeks of oral citicoline. These results in humans support previous in vitro and animal studies and suggest that the administration of oral citicoline may be of use in reversing age-related changes in the brain.
引用
收藏
页码:248 / 254
页数:7
相关论文
共 49 条
[41]   MEMBRANE PHOSPHOLIPID-METABOLISM AND SCHIZOPHRENIA - AN IN-VIVO P-31-MR SPECTROSCOPY STUDY [J].
STANLEY, JA ;
WILLIAMSON, PC ;
DROST, DJ ;
CARR, TJ ;
RYLETT, RJ ;
MORRISONSTEWART, S ;
THOMPSON, RT .
SCHIZOPHRENIA RESEARCH, 1994, 13 (03) :209-215
[42]  
STANLEY JA, 1995, ARCH GEN PSYCHIAT, V52, P399
[43]   CHOLINE INGESTION INCREASES THE RESONANCE OF CHOLINE-CONTAINING COMPOUNDS IN HUMAN BRAIN - AN IN-VIVO PROTON MAGNETIC-RESONANCE STUDY [J].
STOLL, AL ;
RENSHAW, PF ;
DEMICHELI, E ;
WURTMAN, R ;
PILLAY, SS ;
COHEN, BM .
BIOLOGICAL PSYCHIATRY, 1995, 37 (03) :170-174
[44]   Lack of effect of oral choline supplement on the concentrations of choline metabolites in human brain [J].
Tan, J ;
Bluml, S ;
Hoang, T ;
Dubowitz, D ;
Mevenkamp, G ;
Ross, B .
MAGNETIC RESONANCE IN MEDICINE, 1998, 39 (06) :1005-1010
[45]  
VANDENBOOGAART A, 1995, NMR BIOMED, V8, P87, DOI 10.1002/nbm.1940080207
[46]   PHOSPHATIDYLSERINE FUNCTIONS AS THE MAJOR PRECURSOR OF PHOSPHATIDYLETHANOLAMINE IN CULTURED BHK-21-CELLS [J].
VOELKER, DR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (09) :2669-2673
[47]   CELLULAR AND ENZYMIC-SYNTHESIS OF SPHINGOMYELIN [J].
VOELKER, DR ;
KENNEDY, EP .
BIOCHEMISTRY, 1982, 21 (11) :2753-2759
[48]  
WALKEY CJ, 1994, J BIOL CHEM, V269, P5742
[49]   AUTOCANNIBALISM OF CHOLINE-CONTAINING MEMBRANE PHOSPHOLIPIDS IN THE PATHOGENESIS OF ALZHEIMERS-DISEASE - A HYPOTHESIS [J].
WURTMAN, RJ ;
BLUSZTAJN, JK ;
MAIRE, JC .
NEUROCHEMISTRY INTERNATIONAL, 1985, 7 (02) :369-372