Oral supplementation with docosahexaenoic acid and uridine-5’-monophosphate increases dendritic spine density in adult gerbil hippocampus
Open accessAbstract
Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, is an essential component of membrane phosphatides and has been implicated in cognitive functions. Low levels of circulating or brain DHA are associated with various neurocognitive disorders including Alzheimer's disease (AD), while laboratory animals, including animal models of AD, can exhibit improved cognitive ability with a diet enriched in DHA. Various cellular mechanisms have been proposed for DHA's behavioral effects, including increases in cellular membrane fluidity, promotion of neurite extension and inhibition of apoptosis. However, there is little direct evidence that DHA affects synaptic structure in living animals. Here we show that oral supplementation with DHA substantially increases the number of dendritic spines in adult gerbil hippocampus, particularly when animals are co-supplemented with a uridine source, uridine-5'-monophosphate (UMP), which increases brain levels of the rate-limiting phosphatide precursor CTP. The increase in dendritic spines (>30%) is accompanied by parallel increases in membrane phosphatides and in pre- and post-synaptic proteins within the hippocampus. Hence, oral DHA may promote neuronal membrane synthesis to increase the number of synapses, particularly when co-administered with UMP. Our findings provide a possible explanation for the effects of DHA on behavior and also suggest a strategy to treat cognitive disorders resulting from synapse loss.
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Co-administration of uridine, docosahexaenoic acid, and choline can increase the amount of phospholipids, synaptic proteins, dendritic spine density and neurite outgrowth in rodents.
“Several studies in rodents showed that co-administration of uridine, DHA, and choline can increase the amount of phospholipids, synaptic proteins, dendritic spine density and neurite outgrowth (Holguin et al., 2008;Sakamoto et al., 2007;Wurtman et al., 2006).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Sakamoto et al., 2007
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- Authors
- Sakamoto, T., Cansev, M., & Wurtman, R. J.
- Affiliations
- Massachusetts Institute of Technology (US)
- Bursa Uludağ Üni̇versi̇tesi̇ (TR)
- Corresponding author
- Wurtman, Richard J.
- ORCID
- Cansev, Mehmet
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 1182
- Pages
- 50-59
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC2140951
- OpenAlex
- W1997280956
- Cited by
- 188
- References
- 53
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 7 · 2017: 14 · 2016: 10 · 2015: 21 · 2014: 10 · 2013: 16 · 2012: 9
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Bursa Uludag University - AVESIS (submittedVersion)
- Funders
- National Institute of Mental Health (R37MH028783, R01MH028783, MH028783)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- docosahexaenoic acid, uridine 5'-monophosphate, dendritic spine density, hippocampus, omega-3 fatty acids, synaptic structure, CTP, Alzheimer's disease, synaptic loss, gerbils, dietary supplementation
- MeSH terms
- Actins, Administration, Oral, Animals, Docosahexaenoic Acids, Dose-Response Relationship, Drug, Drug Interactions, Gerbillinae, Hippocampus, Male, Membrane Proteins, Models, Biological, Time Factors, Uridine Monophosphate, Glycerophospholipids, Dendritic Spines
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