Synapse formation in the brain can be enhanced by co-administering three specific nutrients

Eur J Pharmacol. 2017 Dec 15:817:20-21. doi: 10.1016/j.ejphar.2017.09.038. Epub 2017 Oct 12.


The memory impairments of early Alzheimer's disease [AD] are thought to result from a deficiency in synapses within the hippocampus and related brain regions. This deficiency could result from an acceleration in synapse turnover - perhaps caused by an endogenous neurotoxin like A-beta oligomers - or from a decrease in the production of the synaptic membrane needed to form new synapses. An AD-associated decrease in synaptogenesis almost certainly does occur, inasmuch as major decreases are also observed in the numbers of hippocampal dendritic spines, the immediate cytologic precursor of glutamatergic synapses. The syntheses of new dendritic spines and synapses can, however, be increased by concurrently raising brain levels of three circulating nutrients - uridine, omega-3 fatty acids docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), and choline. This could provide an additional strategy for restoring synapses and thereby memory. The three nutrients are rate-limiting precursors in the Kennedy Cycle, the pathway which forms the phosphatides that are the major component of synaptic membranes. Uridine also increases the production of synaptic proteins, the other major membrane constituent, and the outgrowth of neurites. Hence administering the three nutrients accelerates synapse formation. These actions of uridine are largely mediated by uridine triphosphate (UTP), which can be released as a neurotransmitter from presynaptic terminals and can then activate P2Y2 receptors. The UTP in neurons can also be converted to cytidylyl triphosphate, CTP, the intermediate utilized in the Kennedy Cycle.

Keywords: Choline; DHA; Dendritic spines; Hippocampus; Memory; Synapses; Synaptic proteins; Uridine.

MeSH terms

  • Animals
  • Brain / drug effects*
  • Choline / administration & dosage*
  • Docosahexaenoic Acids / administration & dosage*
  • Eicosapentaenoic Acid / administration & dosage*
  • Food
  • Humans
  • Synapses / drug effects*


  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Choline