Chronic administration of DHA and UMP improves the impaired memory of environmentally impoverished rats
Open accessAbstract
Living in an enriched environment (EC) during development enhances memory function in adulthood; living in an impoverished environment (IC) impairs memory function. Compounds previously demonstrated to improve memory among IC rats include CDP-choline and uridine monophosphate (UMP). Brain phosphatidylcholine (PC) synthesis utilizes both the uridine formed from the metabolism of exogenous CDP-choline and UMP, and the choline formed from that of CDP-choline. It also uses the polyunsaturated fatty acid (PUFA) DHA, a precursor for the diacylglycerol incorporated into PC. DHA administration also improves cognition in young and aged rodents and humans; its effects on cognitively impaired IC rats have not been characterized. We have thus examined the consequences of administering DHA (300 mg/kg) by gavage, UMP (0.5% in the diet), or both compounds on hippocampal- and striatal-dependent forms of memory among rats exposed to EC or IC conditions for 1 month starting at weaning, and consuming a choline-containing diet. We observe that giving IC rats either dietary UMP or gavaged DHA improves performance on the hidden version of the Morris water maze (all P<0.05), a hippocampal-dependent task; co-administration of both phosphatide precursors further enhances the IC rats' performance on this task (P<0.001). Neither UMP nor DHA, nor giving both compounds, affects the performance of EC rats on the hidden version of the Morris water maze (P>0.05), nor the performance by IC or EC rats on the visible version of the Morris water maze (all P>0.05), a striatal-dependent task. We confirm that co-administration of UMP and DHA to rats increases brain levels of the phosphatides PC, PE, SM, PS, PI, and total brain phospholipid levels (all P<0.05), and show that rearing animals in an enriched environment also elevates brain PC, PS, and PI levels (all P<0.01) and total brain phospholipids (P<0.01) compared with their levels in animals reared in an IC environment. These findings suggest that giving DHA plus UMP can ameliorate memory deficits associated with rearing under impoverished conditions, and that this effect may be mediated in part through enhanced synthesis of brain membrane phosphatides.
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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 Holguin et al., 2008
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“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).”
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- Authors
- Holguin, S., Huang, Y., Liu, J., & Wurtman, R.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Wurtman, Richard
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 191
- Issue
- 1
- Pages
- 11-16
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC2478743
- OpenAlex
- W2003682910
- Cited by
- 57
- References
- 69
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 7 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 8 · 2012: 2
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R37MH028783, MH 28783, R01MH028783)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- docosahexaenoic acid, uridine monophosphate, environmental enrichment, impoverished environment, memory impairment, hippocampal-dependent memory, phosphatidylcholine synthesis, brain phospholipids, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, sphingomyelin, choline, cognitive enhancement, developmental environment
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Brain, Docosahexaenoic Acids, Dose-Response Relationship, Drug, Drug Interactions, Environment, Male, Memory Disorders, Phospholipids, Uridine Monophosphate, Rats, Sprague-Dawley, Maze Learning, Rotarod Performance Test, Rats
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