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

نویسندگان

  • Richard J Wurtman
  • Ismail H Ulus
  • Mehmet Cansev
  • Carol J Watkins
  • Lei Wang
  • George Marzloff
چکیده

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.

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منابع مشابه

Hronic Administration of Docosahexaenoic Acid R Eicosapentaenoic Acid, but Not Arachidonic Acid, Lone or in Combination with Uridine, Increases Brain Hosphatide and Synaptic Protein Levels in Gerbils

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This study examined the effects on cognitive behaviors of giving normal adult gerbils three compounds, normally in the circulation, which interact to increase brain phosphatides, synaptic proteins, dendritic spines, and neurotransmitter release. Animals received supplemental uridine (as its monophosphate, UMP; 0.5%) and choline (0.1%) via the diet, and docosahexaenoic acid (DHA; 300 mg/kg/day) ...

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عنوان ژورنال:
  • Brain research

دوره 1088 1  شماره 

صفحات  -

تاریخ انتشار 2006