Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils

Abstract

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) by gavage, for 4 wk, and then throughout the subsequent period of behavioral training and testing. As shown previously, giving all three compounds caused highly significant (P<0.001) increases in total brain phospholipids and in each major phosphatide; giving DHA or UMP (plus choline) produced smaller increases in some of the phosphatides. DHA plus choline improved performance on the four-arm radial maze, T-maze, and Y-maze tests; coadministering UMP further enhanced these increases. (Uridine probably acts by generating both CTP, which can be limiting in phosphatide synthesis, and UTP, which activates P2Y receptors coupled to neurite outgrowth and protein synthesis. All three compounds also act by enhancing the substrate-saturation of phosphatide-synthesizing enzymes.) These findings demonstrate that a treatment that increases synaptic membrane content can enhance cognitive functions in normal animals.

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

“…In animal studies, Urd was found to improve certain types of memory function (Holguin et al 2008 ;Teather and Wurtman 2003 . Therefore, increased Urd formation may mediate the positive effects of cytidine diphosphocholine (CDPcholine) on verbal memory in aging humans (Spiers et al 1996 ) .…”

Supplementation of docosahexaenoic acid (DHA), vitamin D3 and uridine in combination with six weeks of cognitive and motor training in prepubescent children: a pilot study

“…Since there is no known recommended level for Uridine, we chose a dose well below that used in animal research. Holguin et al 2008 used a dose corresponding to 0.03% of body weight and we consequently decided to use 1 g of uridine, which corresponds to 0.003% of body weight [25]. Blueberry extract was added to protect DHA against oxidation and at the same time to provide a berry like colour of the emulsion.…”

Premature or pathological aging: longevity

“…Studies in animal models of Alzheimer's have demonstrated that the administration of DHA can improve their cognitive performance (HASHIMOTO et al, 2006). Holguin et al (2008) published results of a research along the same lines as that of Sakamoto et al (2007). They used gerbils as experimental animal and the following supplementation: UMP, 0.5%, choline, 0.1% via diet, and DHA, 300mg/kg/day by gavage for 4 weeks, continuing with the same treatment during training and trails.…”