Use of Phosphatide Precursors to Promote Synaptogenesis


Wurtman R. J. , CANSEV M. , Sakamoto T., Ulus I. H.

ANNUAL REVIEW OF NUTRITION, vol.29, pp.59-87, 2009 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 29
  • Publication Date: 2009
  • Doi Number: 10.1146/annurev-nutr-080508-141059
  • Title of Journal : ANNUAL REVIEW OF NUTRITION
  • Page Numbers: pp.59-87
  • Keywords: cognition, Alzheimer's disease, phosphatide, dendritic spine, synaptic membrane, P2Y receptors, FATTY-ACID-COMPOSITION, CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE, PLASMA CHOLINE CONCENTRATIONS, PLUS DOCOSAHEXAENOIC ACID, RAT SYMPATHETIC NEURONS, BRAIN-BARRIER TRANSPORT, ALPHA-LINOLENIC ACID, HAMSTER OVARY CELLS, CDP-CHOLINE, ALZHEIMERS-DISEASE

Abstract

New brain synapses form when a postsynaptic structure, the dendritic spine, interacts with a presynaptic terminal. Brain synapses and dendritic spines, membrane-rich structures, are depleted in Alzheimer's disease,as are some circulating compounds needed for synthesizing phosphatides, the major constituents of synaptic membranes. Animals given three of these compounds, all nutrients-uridine, the omega-3 polyunsaturated fatty acid docosahexaenoic acid, and choline-develop increased levels of brain phosphatides and of proteins that are concentrated within synaptic membranes (e.g., PSD-95, synapsin-1), improved cognition, and enhanced neurotransmitter release. The nutrients work by increasing the substrate-saturation of low-affinity enzymes that synthesize the phosphatides. Moreover, uridine and its nucleotide metabolites activate brain P2Y receptors, which control neuronal differentiation and synaptic protein synthesis. A preparation containing these compounds is being tested for treating Alzheimer's disease.