Browsing by Author "Marzloff, George"
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Item Giving uridine and/or docosahexaenoic acid orally to rat dams during gestation and nursing increases synaptic elements in brains of weanling pups(Karger, 2009-04) Marzloff, George; Sakamoto, Toshimasa; Wurtman, Richard J.; Cansev, Mehmet; Ulus, İsmail Hakkı; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; 8872816100; 7004271086Developing neurons synthesize substantial quantities of membrane phospholipids in producing new synapses. We investigated the effects of maternal uridine (as uridine-5′-monophosphate) and docosahexaenoic acid supplementation on pups' brain phospholipids, synaptic proteins and dendritic spine densities. Dams consumed neither, 1 or both compounds for 10 days before parturition and 20 days while nursing. By day 21, brains of weanlings receiving both exhibited significant increases in membrane phosphatides, various pre- and postsynaptic proteins (synapsin-1, mGluR1, PSD-95), and in hippocampal dendritic spine densities. Administering these phosphatide precursors to lactating mothers or infants could be useful for treating developmental disorders characterized by deficient synapses.Item Oral uridine (UMP) plus docosahexaenoic acid (DHA) increases phospholipids and synaptic proteins in gerbil brain(Wiley, 2006) Wurtman, Richard; Watkins, Carol J..; Wang, L.; Marzloff, George; Cansev, Mehmet; Ulus, İsmail Hakkı; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; D-5340-2015; M-9071-2019Item Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally(Elsevier Science, 2006-05-09) Wurtman, Richard J.; Watkins, Carol J.; Wang, Lei; Marzloff, George; Ulus, İsmail Hakkı; Cansev, Mehmet; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0003-2918-5064; D-5340-2015; 7004271086; 8872816100The synthesis of brain phosphatidy1choline 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 phosphatidy1choline 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..