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

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

doi:10.1016/j.brainres.2006.03.019

Cited by 157 publications

(186 citation statements)

References 39 publications

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“…Because these effects of NGF would confound any stimulation of PC synthesis that might have been caused by PUFAs, our experiments used undifferentiated PC12 cells in defined medium. When gerbils received uridine in the diet and DHA by gavage, significant increases in brain phospholipids and in specific synaptic proteins were observed, while the increases caused by uridine or DHA alone were less pronounced [21].…”

Section: Discussionmentioning

confidence: 97%

“…We recently reported in vivo studies showing that repeated administration of DHA can increase brain levels of phosphatides and of certain synaptic proteins, and that these responses are enhanced if animals also receive choline and uridine monophosphate, which raises brain CTP concentrations [21]. In order to characterize the effects of various PUFAs on phospholipid biosynthesis we have used in the present studies undifferentiated, non-transfected PC12 cells.…”

Section: Introductionmentioning

confidence: 99%

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Polyunsaturated fatty acids stimulate phosphatidylcholine synthesis in PC12 cells

Richardson

Wurtman

2007

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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The synthesis of phospholipids in mammalian cells is regulated by the availability of three critical precursor pools: those of choline, cytidine triphosphate and diacylglycerol. Diacylglycerols containing polyunsaturated fatty acids (PUFAs) apparently are preferentially utilized for phosphatide synthesis. PUFAs are known to play an important role in the development and function of mammalian brains. We therefore studied the effects of unsaturated, monounsaturated and polyunsaturated fatty acids on the overall rates of phospholipid biosynthesis in PC12 rat pheochromocytoma cells. Docosahexaenoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (AA, 20:4n-6) all significantly stimulated the incorporation of 14 C-choline into total cellular phospholipids. In contrast, monounsaturated oleic acid (OA) and the unsaturated palmitic (PA) and stearic (SA) acids did not have this effect. The action of DHA was concentration-dependent between 5 and 50 μM; it became statistically significant by 3 hrs after DHA treatment and then increased over the ensuing 3 hours. DHA was preferentially incorporated into phosphatidylethanolamine (PE) and phosphatidylserine (PS), while AA predominated in phosphatidylcholine (PC).

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Polyunsaturated fatty acids stimulate phosphatidylcholine synthesis in PC12 cells

Richardson

Wurtman

2007

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…PC synthesis requires the use of three circulating compounds; choline; a pyrimidine such as uridine; and a polyunsaturated fatty acid (PUFA) such as docosahexaenoic acid (DHA) [14]. Consumption of DHA during development [15] or by aged rats [16] can improve learning and memory, and chronic administration of either the uridine source UMP, or especially, of DHA, can increase brain phosphatide levels [14].…”

Section: Introductionmentioning

confidence: 99%

“…Consumption of DHA during development [15] or by aged rats [16] can improve learning and memory, and chronic administration of either the uridine source UMP, or especially, of DHA, can increase brain phosphatide levels [14].…”

Section: Introductionmentioning

confidence: 99%

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats

Holguin

Huang

Liu

et al. 2008

Behavioural Brain Research

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Living in an enriched environment (EC) during development enhances memory function in adulthood; living in an impoverished environment (IC) impairs memory function. Compounds previously demonstrated to improve memory among IC rats include CDP-choline and uridine monophosphate (UMP). Brain phosphatidylcholine (PC) synthesis utilizes both the uridine formed from the metabolism of exogenous CDP-choline and UMP, and the choline formed from that of CDPcholine. It also uses the polyunsaturated fatty acid (PUFA) DHA, a precursor for the diacylglycerol incorporated into PC. DHA administration also improves cognition in young and aged rodents and humans; its effects on cognitively-impaired IC rats have not been characterized. We have thus examined the consequences of administering DHA (300 mg/kg ) by gavage, UMP (0.5% in the diet), or both compounds on hippocampal-and striatal-dependent forms of memory among rats exposed to EC or IC conditions for 1 month starting at weaning, and consuming a choline-containing diet. We observe that giving IC rats either dietary UMP or gavaged DHA improves performance on the hidden version of the Morris water maze (all P<0.05), a hippocampal-dependent task; coadministration of both phosphatide precursors further enhances the IC rats' performance on this task (P<0.001). Neither UMP, DHA, nor both compounds affects the performance of EC rats on the hidden version of the Morris water maze (P>0.05), nor the performance by IC or EC rats on the visible version of the Morris water maze (all P>0.05), a striatal-dependent task. We confirm that coadministration of UMP and DHA to rats increases brain levels of the phosphatides PC, PE, SM, PS, PI, and total brain phospholipid levels (all p<0.05), and show that rearing animals in an enriched environment also elevates brain PC, PS, and PI levels (all p<0.01) and total brain phospholipids (p<0.01) compared with their levels in animals reared in an IC environment. These findings suggest that giving DHA plus UMP can ameliorate memory deficits associated with rearing under impoverished conditions, and that this effect may be mediated in part through enhanced synthesis of brain membrane phosphatides.

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“…these include precursors for membrane phosphatidylation such as uridine, choline and omega-3 polyunsaturated fatty acids (4)(5)(6). Reports have also indicated that combining these nutrients may improve cognition and increase hippocampal dendritic spines (7), again suggesting a positive effect on the formation of new synapses (8)(9)(10).…”

mentioning

confidence: 99%

Efficacy of a medical food on cognition in Alzheimer's Disease: Results from secondary analyses of a randomized, controlled trial

Kamphuis

Verhey

Rikkert

et al. 2011

The Journal of nutrition, health and aging

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1. Nutricia advanced medical Nutrition, danone Research, centre for specialised Nutrition, Wageningen, the Netherlands; 2. utrecht institute for Pharmaceutical sciences (uiPs), utrecht university, the Netherlands; 3. alzheimer centre limburg, school for mental Health and Neuroscience, maastricht university medical centre, the Netherlands; 4. alzheimer centre Nijmegen, department of Geriatrics, Radboud university Nijmegen medical centre, the Netherlands; 5. department of Health sciences, Vu university medical center, amsterdam, the Netherlands; 6. alzheimer centre, Vu university medical center, amsterdam, the Netherlands. correspondence to: Professor Philip scheltens, department of Neurology and alzheimer center, Vu university medical center, de Boelelaan 1117, 1081 HV amsterdam, the Netherlands, p.scheltens@vumc.nl, tel: +31 (0) 20 444 0816, abstract: Objective: to investigate the extent that baseline cognitive impairment and intake adherence affected the 13-item alzheimer's disease assessment scale -cognitive subscale (adas-cog) intervention response of a medical food in alzheimer's disease (ad) patients. Design/setting/participants /intervention/measurements: this analysis was performed on data from a proof-of-concept study, consisting of a 12-week, double-blind, randomized, controlled, multicenter trial, followed by a similarly designed 12-week extension study. Patients with mild ad (mini-mental state examination [mmse] score of 20-26) were randomized to receive active or control product as a 125 ml daily drink. One of the co-primary outcome measures was the 13-item adas-cog. in this analysis, the study population was divided into two subgroups: patients with 'low' baseline adas-cog scores (<25.0) and patients with 'high' baseline adas-cog scores (≥25.0). Repeated measures models (Rmm) were used to determine the relationship between adas-cog score and intervention. Results: a significant treatment effect (F[1,319]=4.0, p=0.046) was shown in patients with 'high' baseline adas-cog, but not in patients with 'low' baseline adas-cog (F[1,250]=1.25, p=0.265). Overall, intake adherence was significantly correlated with adas-cog improvement in the active product group (correlation coefficient=-0.260; p=0.019), but not the control group. Conclusion: these data indicate that baseline adas-cog significantly influenced the effect of souvenaid intervention on adas-cog outcome. a higher intake of active study product was also associated with greater cognitive benefit. these findings highlight the potential benefits of souvenaid in ad patients and warrant confirmation in larger, controlled studies.

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

Cited by 157 publications

References 39 publications

Polyunsaturated fatty acids stimulate phosphatidylcholine synthesis in PC12 cells

Polyunsaturated fatty acids stimulate phosphatidylcholine synthesis in PC12 cells

Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats

Efficacy of a medical food on cognition in Alzheimer's Disease: Results from secondary analyses of a randomized, controlled trial

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