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]. Age related loss of synapses has been demonstrated during normal ageing. However in people with Alzheimer’s disease, there is a 20-25% loss of synapses compared with 10-15% during normal ageing [3,4]. Studies suggest that synapse loss may even precede and exceed neuronal loss. Therefore to mitigate neuronal loss, which underlies synaptic loss in people with Alzheimer’s disease, there is a greater requirement to synthesise new membranes compared with the requirement in normal health.

New synapses are formed when a postsynaptic structure (dendritic spine) interacts with a presynaptic nerve terminal [5]. Since dendritic spine outgrowth precedes synapse formation, the rate of synaptogenesis is dependent on the availability of dendritic spines.

Synapses and dendritic spines consist of neuronal membranes, which are composed of phospholipids. Phosphatidylcholine is the most abundant phospholipid in the brain, which is generated primarily via the Kennedy pathway [2]. The production of phospholipids via this pathway is positively affected by the availability of the required nutritional precursors uridine monophosphate, choline and omega 3 fatty polyunsaturated fatty acids.

 References

  1. Yi JJ and Ehlers MD. Ubiquitin and protein turnover in synapse function. Neuron. 2005;47:629-632.
  2. Kennedy EP, Weiss SB (1956) The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem 222, 193-214
  3. Masliah E, Mallory M, Hansen L, DeTeresa R, Terry RD (1993) Quantitative synaptic alterations in the human neocortex during normal aging. Neurology 43, 192-197
  4. Liu X, Erikson C, Brun A (1996) Cortical synaptic changes and gliosis in normal aging, Alzheimer’s disease and frontal lobe degeneration. Dementia 7, 128-134
  5. Toni N, Teng EM, Bushong EA, Aimone JB, Zhao C, Consiglio A, van Praag H, Martone ME, Ellisman MH, Gage FH (2007) Synapse formation on neurons born in the adult hippocampus. Nat Neurosci 10, 727-734