Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides
dc.contributor.author | Wurtman, Richard | |
dc.contributor.buuauthor | Cansev, Mehmet | |
dc.contributor.buuauthor | Ulus, İsmail Hakkı | |
dc.contributor.department | Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı. | tr_TR |
dc.contributor.researcherid | D-5340-2015 | tr_TR |
dc.contributor.researcherid | M-9071-2019 | tr_TR |
dc.contributor.scopusid | 8872816100 | tr_TR |
dc.contributor.scopusid | 7004271086 | tr_TR |
dc.date.accessioned | 2021-11-11T06:43:52Z | |
dc.date.available | 2021-11-11T06:43:52Z | |
dc.date.issued | 2009-03 | |
dc.description.abstract | Objective: The loss of cortical and hippocampal synapses is a universal hallmark of Alzheimer's disease, and probably underlies its effects on cognition. Synapses are formed from the interaction of neurites projecting from "presynaptic" neurons with dendritic spines projecting from "postsynaptic" neurons. Both of these structures are vulnerable to the toxic effects of nearby amyloid plaques, and their loss contributes to the decreased number of synapses that characterize the disease. A treatment that increased the formation of neurites and dendritic spines might reverse this loss, thereby increasing the number of synapses and slowing the decline in cognition. Design setting, Participants, Intervention, Measurements and Results: We observe that giving normal rodents uridine and the omega-3 fatty acid docosahexaenoic acid (DHA) orally can enhance dendritic spine levels (3), and cognitive functions (32). Moreover this treatment also increases levels of biochemical markers for neurites (i.e., neurofilament-M and neurofilament-70) (2) in vivo, and uridine alone increases both these markers and the outgrowth of visible neurites by cultured PC-12 cells (9). A phase 2 clinical trial, performed in Europe, is described briefly. Discussion and Conclusion: Uridine and DHA are circulating precursors for the phosphatides in synaptic membranes, and act in part by increasing the substrate-saturation of enzymes that synthesize phosphatidylcholine from CTP (formed from the uridine, via UTP) and from diacylglycerol species that contain DHA: the enzymes have poor affinities for these substrates, and thus are unsaturated with them, and only partially active, under basal conditions. The enhancement by uridine of neurite outgrowth is also mediated in part by UTP serving as a ligand for neuronal P2Y receptors. Moreover administration of uridine with DHA activates many brain genes, among them the gene for the m-1 metabotropic glutamate receptor [Cansev, et al, submitted]. This activation, in turn, increases brain levels of that gene's protein product and of such other synaptic proteins as PSD-95, synapsin-1, syntaxin-3 and F-actin, but not levels of non-synaptic brain proteins like beta-tubulin. Hence it is possible that giving uridine plus DHA triggers a neuronal program that, by accelerating phosphatide and synaptic protein synthesis, controls synaptogenesis. If administering this mix of phosphatide precursors also increases synaptic elements in brains of patients with Alzheimer's disease, as it does in normal rodents, then this treatment may ameliorate some of the manifestations of the disease. | en_US |
dc.description.sponsorship | Center for Brain Sciences and Metabolism Charitable Trust | en_US |
dc.description.sponsorship | United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) (R37MH028783) | en_US |
dc.identifier.citation | Wurtman, R. J. vd. (2009). "Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides". Journal of Nutrition Health & Aging, 13(3), 189-197. | en_US |
dc.identifier.endpage | 197 | tr_TR |
dc.identifier.issn | 1279-7707 | |
dc.identifier.issue | 3 | tr_TR |
dc.identifier.pubmed | 19262950 | tr_TR |
dc.identifier.scopus | 2-s2.0-63249114054 | tr_TR |
dc.identifier.startpage | 189 | tr_TR |
dc.identifier.uri | https://doi.org/10.1007/s12603-009-0056-3 | |
dc.identifier.uri | https://link.springer.com/article/10.1007%2Fs12603-009-0056-3 | |
dc.identifier.uri | http://hdl.handle.net/11452/22618 | |
dc.identifier.volume | 13 | tr_TR |
dc.identifier.wos | 000265941200005 | tr_TR |
dc.indexed.pubmed | Pubmed | en_US |
dc.indexed.scopus | Scopus | en_US |
dc.indexed.wos | SCIE | en_US |
dc.language.iso | en | en_US |
dc.publisher | Springer | en_US |
dc.relation.collaboration | Yurt dışı | tr_TR |
dc.relation.journal | Journal of Nutrition Health & Aging | tr_TR |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi | tr_TR |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.subject | Ctp-phosphocholine cytidylyltransferase | en_US |
dc.subject | Dependent nucleoside transport | en_US |
dc.subject | Polyunsaturated fatty-acids | en_US |
dc.subject | Phospholipase-c treatment | en_US |
dc.subject | Long-term potentiation | en_US |
dc.subject | Hamster ovary cells | en_US |
dc.subject | Adult rat-brain | en_US |
dc.subject | Docosahexaenoic acid | en_US |
dc.subject | Dendritic spines | en_US |
dc.subject | Arachidonic-acid | en_US |
dc.subject | Geriatrics & gerontology | en_US |
dc.subject | Nutrition & dietetics | en_US |
dc.subject | Rodentia | en_US |
dc.subject.emtree | Amyloid | en_US |
dc.subject.emtree | Beta tubulin | en_US |
dc.subject.emtree | Cervonic acid | en_US |
dc.subject.emtree | Cytidine triphosphate | en_US |
dc.subject.emtree | Diacylglycerol | en_US |
dc.subject.emtree | F actin | en_US |
dc.subject.emtree | Gene product | en_US |
dc.subject.emtree | Metabotropic receptor | en_US |
dc.subject.emtree | Neurofilament M protein | en_US |
dc.subject.emtree | Neurofilament protein | en_US |
dc.subject.emtree | Phosphatidylcholine | en_US |
dc.subject.emtree | Phospholipid | en_US |
dc.subject.emtree | Postsynaptic density protein 95 | en_US |
dc.subject.emtree | Purinergic P2Y receptor | en_US |
dc.subject.emtree | Synapsin I | en_US |
dc.subject.emtree | Syntaxin | en_US |
dc.subject.emtree | Uridine | en_US |
dc.subject.emtree | Uridine triphosphate | en_US |
dc.subject.emtree | Alzheimer disease | en_US |
dc.subject.emtree | Article | en_US |
dc.subject.emtree | Brain cortex | en_US |
dc.subject.emtree | Cell strain | en_US |
dc.subject.emtree | Clinical trial | en_US |
dc.subject.emtree | Cognition | en_US |
dc.subject.emtree | Dendrite | en_US |
dc.subject.emtree | Enzyme substrate complex | en_US |
dc.subject.emtree | Gene activation | en_US |
dc.subject.emtree | Hippocampus | en_US |
dc.subject.emtree | Human | en_US |
dc.subject.emtree | In vivo study | en_US |
dc.subject.emtree | Nerve fiber growth | en_US |
dc.subject.emtree | Neurite | en_US |
dc.subject.emtree | Nonhuman | en_US |
dc.subject.emtree | Phospholipid synthesis | en_US |
dc.subject.emtree | Postsynaptic membrane | en_US |
dc.subject.emtree | Presynaptic nerve | en_US |
dc.subject.emtree | Priority journal | en_US |
dc.subject.emtree | Protein synthesis | en_US |
dc.subject.emtree | Senile plaque | en_US |
dc.subject.emtree | Synapse | en_US |
dc.subject.emtree | Synaptic membrane | en_US |
dc.subject.emtree | Synaptogenesis | en_US |
dc.subject.mesh | Administration, oral | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Biological markers | en_US |
dc.subject.mesh | Brain | en_US |
dc.subject.mesh | Brain chemistry | en_US |
dc.subject.mesh | Clinical trials as topic | en_US |
dc.subject.mesh | Cognition | en_US |
dc.subject.mesh | Docosahexaenoic acids | en_US |
dc.subject.mesh | Gerbillinae | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Neurites | en_US |
dc.subject.mesh | Phospholipids | en_US |
dc.subject.mesh | Synapses | en_US |
dc.subject.mesh | Uridine | en_US |
dc.subject.scopus | Choline Phosphate Cytidylyltransferase; Phosphatidylcholines; Citicoline | en_US |
dc.subject.wos | Geriatrics & gerontology | en_US |
dc.subject.wos | Nutrition & dietetics | en_US |
dc.title | Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides | en_US |
dc.type | Review | |
dc.wos.quartile | Q3 | en_US |
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