Dietary supplementation with uridine-5'-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat

Brain Res. 2007 Feb 16;1133(1):42-8. doi: 10.1016/j.brainres.2006.11.048. Epub 2006 Dec 19.

Abstract

The biosynthesis of brain membrane phosphatides, e.g., phosphatidylcholine (PtdCho), may utilize three circulating compounds: choline, uridine (a precursor for UTP, CTP, and CDP-choline), and a PUFA (e.g., docosahexaenoic acid); moreover, oral administration of the uridine source uridine-5'-monophosphate (UMP) can significantly increase levels of the phosphatides throughout the rodent brain. Since PtdCho can provide choline for acetylcholine (ACh) synthesis, we determined whether UMP administration also affects ACh levels in striatum and striatal extracellular fluid, in aged and young rats. Among aged animals consuming a UMP-containing diet (2.5%, w/w) for 1 or 6 weeks, baseline ACh levels in striatal dialysates rose from 73 fmol/min to 148 or 197 fmol/min (P<0.05). Consuming a lower dose (0.5%) for 1 week produced a smaller but still significant increase (from 75 to 92 fmol/min, P<0.05), and elevated striatal ACh content (by 16%; P<0.05). Dietary UMP (0.5%, 1 week) also amplified the increase in ACh caused by giving atropine (10 microM in the aCSF); atropine alone increased ACh concentrations from 81 to 386 fmol/min in control rats and from 137 to 680 fmol/min in those consuming UMP (P<0.05). Young rats eating the UMP-containing diet exhibited similar increases in basal ECF ACh (from 105 to 118 fmol/min) and in the increase produced by atropine (from 489 to 560 fmol/min; P<0.05). These data suggest that giving a uridine source may enhance some cholinergic functions, perhaps by increasing brain phosphatide levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Aging / physiology*
  • Animals
  • Atropine / pharmacology
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Food, Formulated*
  • Male
  • Membrane Lipids / metabolism
  • Muscarinic Antagonists / pharmacology
  • Phosphatidylcholines / metabolism
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Inbred F344
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • Uridine Monophosphate / metabolism
  • Uridine Monophosphate / pharmacology*

Substances

  • Membrane Lipids
  • Muscarinic Antagonists
  • Phosphatidylcholines
  • Atropine
  • Uridine Monophosphate
  • Acetylcholine