Oral Administration of Phosphatide Precursors Enhances Learning and Memory by Promoting Synaptogenesis
Chronic oral administration of various membrane phosphatide precursors (e.g., cytidine, uridine, polyunsaturated fatty acids, and choline) enhances learning and memory and improves diminished cognitive performance in experimental animals. In addition, treatment with a mixture containing the phosphatide precursors uridine, docosahexaenoic acid (DHA), and choline has been shown in a recent clinical trial to improve cognitive functions in newly recognized Alzheimer’s patients. Evidence obtained from experimental studies suggests that the most likely mechanism by which this treatment improves cognition is the enhancement in numbers of brain synapses. First off, chronic oral administration of membrane phosphatide precursors increases the levels of brain membrane phosphatides and of proteins that are known to be concentrated within synaptic membranes (e.g., PSD-95; synapsin-1). In addition, numbers of dendritic spines are enhanced after treatment with membrane phosphatide precursors. Since new brain synapses form when a dendritic spine interacts with a presynaptic terminal, it is therefore reasonable to assume that enhancing synaptogenesis is at least one of the mechanisms by which this treatment enhances learning and memory. Additional evidence supporting this hypothesis comes from studies which demonstrated enhanced release of such neurotransmitters as acetylcholine and dopamine. This review summarizes the findings on experimental and human studies of enhanced cognitive function following chronic administration of membrane phosphatide precursors and the mechanism by which brain biochemistry and structure are altered in order to enhance learning and memory.
KeywordsDendritic Spine Choroid Plexus Synaptic Protein Synaptic Membrane Choline Kinase
Polyunsaturated fatty acid
Data presented here are derived from studies in Prof. Richard Wurtman’s laboratory. The authors thank Prof. Wurtman for his support during preparation of this review.
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