Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally

Richard J. Wurtman, Ismail H. Ulus, Mehmet Cansev, Carol J. Watkins, Lei Wang, George Marzloff

Research output: Contribution to journalArticle

118 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)83-92
Number of pages10
JournalBrain Research
Volume1088
Issue number1
DOIs
StatePublished - May 9 2006
Externally publishedYes

Fingerprint

Gerbillinae
Docosahexaenoic Acids
Uridine
Phospholipids
Choline
Synaptic Membranes
Phosphatidylcholines
Brain
Uridine Triphosphate
Proteins
Synapsins
Uridine Monophosphate
Cytidine Triphosphate
Cytoskeletal Proteins
Neurites
Tubulin
Synapses
Alzheimer Disease
Diet
Enzymes

Keywords

  • Alzheimer's disease
  • Docosahexaenoic acid
  • Neuronal membrane
  • Phosphatidylcholine
  • Synaptic protein
  • Uridine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. / Wurtman, Richard J.; Ulus, Ismail H.; Cansev, Mehmet; Watkins, Carol J.; Wang, Lei; Marzloff, George.

In: Brain Research, Vol. 1088, No. 1, 09.05.2006, p. 83-92.

Research output: Contribution to journalArticle

Wurtman, Richard J. ; Ulus, Ismail H. ; Cansev, Mehmet ; Watkins, Carol J. ; Wang, Lei ; Marzloff, George. / Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. In: Brain Research. 2006 ; Vol. 1088, No. 1. pp. 83-92.
@article{c5bd1ece263d4e91ae12322a9559466d,
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.",
keywords = "Alzheimer's disease, Docosahexaenoic acid, Neuronal membrane, Phosphatidylcholine, Synaptic protein, Uridine",
author = "Wurtman, {Richard J.} and Ulus, {Ismail H.} and Mehmet Cansev and Watkins, {Carol J.} and Lei Wang and George Marzloff",
year = "2006",
month = "5",
day = "9",
doi = "10.1016/j.brainres.2006.03.019",
language = "English (US)",
volume = "1088",
pages = "83--92",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally

AU - Wurtman, Richard J.

AU - Ulus, Ismail H.

AU - Cansev, Mehmet

AU - Watkins, Carol J.

AU - Wang, Lei

AU - Marzloff, George

PY - 2006/5/9

Y1 - 2006/5/9

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Docosahexaenoic acid

KW - Neuronal membrane

KW - Phosphatidylcholine

KW - Synaptic protein

KW - Uridine

UR - http://www.scopus.com/inward/record.url?scp=33646592555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646592555&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2006.03.019

DO - 10.1016/j.brainres.2006.03.019

M3 - Article

C2 - 16631143

AN - SCOPUS:33646592555

VL - 1088

SP - 83

EP - 92

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -