Giving Uridine and/or Docosahexaenoic Acid Orally to Rat Dams during Gestation and Nursing Increases Synaptic Elements in Brains of Weanling Pups

Abstract

Developing 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.

A specific multi-nutrient enriched diet enhances hippocampal cholinergic transmission in aged rats

“…Hence, supplementation with FC may produce more or larger synapses or synaptic vesicles which may contribute to increasing hippocampal ACh content and release. In accordance with our findings, the increase in amounts of membrane phospholipids after oral supplementation of DHA and/or UMP reported in previous studies Cansev et al, 2008Cansev et al, , 2009Sakamoto et al, 2007;Wurtman et al, 2006) were also shown to be associated with increased levels of specific presynaptic and postsynaptic proteins.…”

Neuroprotective effects of uridine in a rat model of neonatal hypoxic–ischemic encephalopathy

“…Uridine also serves as a precursor of membrane phosphatides and exogenous administration of uridine enhances CDP-choline levels in PC12 cells [23], striatal slices [27] and rodent brains [8]. Chronic supplementation with uridine-5-monophosphate (UMP) increases levels of phospholipids, synaptic proteins and leads to synaptogenesis in adult [24,34] and newborn rodents [6]. Evidence that uridine might confer benefit under degenerative conditions has been provided by in vitro glucose deprivation studies [10,11] as well as in vivo rat model of Parkinson's [7].…”

The Antiepileptic Potential of Nucleosides

“…Uridine has already been tested in human studies [360][361][362][363][364], and a decrease in seizure activity in response to Urd has been demonstrated in humans [363][364][365]. Uridine is also found in mother's milk and may be useful as a nutritional supplement during early postnatal development [366,367]; consequently, Urd is a well tolerable drug, which showed low toxicity [63,64,360,361]. These results suggest that Urd and/or its analogues [83,356] may be effective and safe drugs to treat epilepsy [31].…”