Wurtman, RichardSakamoto, Joshimasa2021-11-092021-11-092008-01Cansev, M. vd. (2008). ''Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses''. Alzheimers & Dementia, 4(1), Supplement 1, S153-S168.1552-52601552-5279https://www.sciencedirect.com/science/article/abs/pii/S1552526007006280https://doi.org/10.1016/j.jalz.2007.10.005http://hdl.handle.net/11452/22588Although cognitive performance in humans and experimental animals can be improved by administering omega-3 fatty acid docosahexaenoic acid (DHA), the neurochemical mechanisms underlying this effect remain uncertain. In general, nutrients or drugs that modify brain function or behavior do so by affecting synaptic transmission, usually by changing the quantities of particular neurotransmitters present within synaptic clefts or by acting directly on neurotransmitter receptors or signal-transduction molecules. We find that DHA also affects synaptic transmission in mammalian brain. Brain cells of gerbils or rats receiving this fatty acid manifest increased levels of phosphatides and of specific presynaptic or postsynaptic proteins. They also exhibit increased numbers of dendritic spines on postsynaptic neurons. These actions are markedly enhanced in animals that have also received the other two circulating precursors for phosphatidylcholinc, uridine (which gives rise to brain uridine diphosphate and cytidine triphosphate) and choline (which gives rise to phosphocholine). The actions of DHA acre reproduced by eicosapentaenoic acid, another omega-3 compound, but not by omega-6 fatty acid arachidonic acid. Administration of circulating phosphatide precursors can also increase neurotransmitter release (acetylcholine, dopamine) and affect animal behavior. Conceivably, this treatment might have use in patients with the synaptic loss that characterizes Alzheimer's disease or other neurodegenerative diseases or occurs after stroke or brain injury.eninfo:eu-repo/semantics/openAccessPhosphatideUridineDocosahexaenoic acidPrecursorSynaptic membraneDendritic spineAlzheimer's diseasePolyunsaturated fatty-acidsCtp-phosphocholine cytidylyltransferaseDependent nucleoside transportPhospholipase-c treatmentLong-term potentiationRat-liver microsomesHamster ovary cellsCdp-choline levelsDocosahexaenoic acidDendritic spinesNeurosciences & neurologyAdministrationOralAnimalsBrainBrain diseasesCell membraneCholineDocosahexaenoic acidsHumansMembrane lipidsPhospholipidsProdrugsSynapsesSynaptic transmissionUridineArticle0002526997000272-s2.0-380491161181531684118631994Clinical neurologyCholine Phosphate Cytidylyltransferase; Phosphatidylcholines; CiticolineAcetylcholineArachidonic acidBeta tubulinCholineCholine kinaseCholine phosphate cytidylyltransferaseCholinephosphotransferaseCytidine diphosphateCytidine triphosphateDocosahexaenoic acidDopamineGlutamate receptor 1Icosapentaenoic acidNeurofilament proteinNeurotransmitterNeurotransmitter receptorOmega 3 fatty acidPhospholipidPostsynaptic density protein 95Synapsin ISyntaxinSyntaxin 3Unclassified drugUridineUridine phosphateAcetylcholine releaseAlzheimer diseaseAnimal behaviorBehavior modificationBrain cellBrain functionBrain injuryDegenerative diseaseDendritic spineDiet supplementationDopamine releaseDrug bioavailabilityDrug dose comparisonDrug metabolismDrug uptakeEditorialGerbilGumanMammal cellNerve cell plasticityNeurochemistryNeurotransmitter releaseNonhumanPhospholipid synthesisPriority journalSignal transductionStrokeSynapseSynaptic transmissionSynaptogenesis