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Supporting synapse formation

Synapse formation depends on neuronal membrane synthesis, which is supported by a specific combination of nutrients working together.

A specific combination of nutrients is required to support synapse formation through the Kennedy pathway

Synapse formation and loss (synaptic plasticity) occurs throughout life, with individual brain synapses being continuously remodelled [1,2]. Synapses consist of neuronal membranes, which are primarily composed of phospholipids [1,2].

Neuronal membrane synthesis occurs via the Kennedy pathway, where specific nutritional precursors (docosahexaenoic acid [DHA], eicosapentaenoic acid [EPA], uridine (as uridine monophosphate), phospholipids and choline) are required for the synthesis of phosphatidyl-choline, the most abundant phospholipid in the brain [3-13]. Specific co-factors  (B-vitamins, vitamin E, C and selenium) enhance the bioavailability of these nutritional precursors, increasing substrate-saturation of the low-affinity enzymes involved in brain phospholipid synthesis [3-13]. If any one of these precursors is not available, that specific step in the pathway becomes rate-limiting in the process of phospholipid synthesis. 

Preclinical research demonstrates the link between providing specific nutritional components and increasing levels of brain phospholipids, dendritic spines and neurite outgrowth [3,5,14], with the greatest effects being observed when combinations of nutrients were used. Administration of these nutrients also improves learning and memory in preclinical models [6,7]. 

These research findings provided the scientific rationale for the formulation of Souvenaid. Souvenaid has been clinically proven to improve memory in two, double-blind, randomised, controlled clinical trials, in mild Alzheimer’s disease patients [15,16]. 

  • Souvenaid contains a specific combination of nutrients designed to support synapse formation

    Souvenaid contains a specific combination of nutrients designed to support synapse formation

    Key nutritional precursors and co-factors are required for the formation of phosphatidylcholine [9], which is the key component of neuronal membranes.

  • This combination of nutrients is required in the Kennedy pathway to form phospholipids

    This combination of nutrients is required in the Kennedy pathway to form phospholipids

    The synthesis of neuronal membranes occurs via the Kennedy pathway which is dependent on the availability of specific nutritional precursors. If any one of these precursors is not available, that specific step in the pathway becomes rate-limiting.Souvenaid - HDIW - Slide 02

  • The phospholipids are incorporated into neuronal membranes

    The phospholipids are incorporated into neuronal membranes

    Phosphatidylcholine is one of the major components of neuronal membranes.

  • Increased neuronal membrane synthesis supports synapse formation

    Increased neuronal membrane synthesis supports synapse formation

    A new brain synapse is formed when a dendritic spine (postsynaptic structure) interacts with a presynaptic nerve terminal, which is an essential process in neuronal membrane synthesis.

References

  1. Yi JJ and Ehlers MD. Ubiquitin and protein turnover in synapse function. Neuron. 2005;47:629-632.
  2. Kennedy EP and Weiss SB. The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem. 1956;222:193-214. 
  3. Wurtman RJ, et al. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006;1088:83-92.
  4. Cansev M, et al. Restorative effects of uridine plus docosahexaenoic acid in a rat model of Parkinson's disease. Neurosci Res. 2008;62:206-209.
  5. Sakamoto T, et al. Oral supplementation with docosahexaenoic acid and uridine-5'-monophosphate increases dendritic spine density in adult gerbil hippocampus. Brain Res. 2007;1182:50-59.
  6. Holguin S, et al. Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats. Behav Brain Res. 2008;191:11-16.
  7. Holguin S, et al. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. FASEB J. 2008;22:3938-3946.
  8. Cansev M, et al.  Giving uridine and/or docosahexaenoic acid orally to rat dams during gestation and nursing increases synaptic elements in brains of weanling pups. Dev Neurosci. 2009;31:181-192.
  9. Cansev M and Wurtman RJ. Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils. Neuroscience. 2007;148:421-431.
  10. Wang L, et al. Dietary supplementation with uridine-5'-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat. Brain Res. 2007;1133:42-48.
  11. Richardson UI, et al. Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells. Brain Res. 2003;971:161-167.
  12. Richardson UI and Wurtman RJ. Polyunsaturated fatty acids stimulate phosphatidylcholine synthesis in PC12 cells. Biochim Biophys Acta. 2007;1771:558-563.
  13. van Wijk N, et al. Plasma choline concentration varies with different dietary levels of vitamins B6, B12 and folic acid in rats maintained on choline-adequate diets. Br J Nutr. 2012;107:1408-12.
  14. Pooler AM, et al. Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12. Neuroscience. 2005;134:207-214.
  15. Scheltens P, et al. Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial. Alzheimers Dement. 2010;6:1-10.e1.
  16. Scheltens P, et al. Efficacy of Souvenaid in mild Alzheimer's disease: results from a randomized, controlled trial. J Alzheimer’s Dis. 2012;31:225–236.