Chronic Administration of Docosahexaenoic Acid Ameliorates the Impairment of Spatial Cognition Learning Ability in Amyloid β–Infused Rats
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We investigated whether administration of docosahexaenoic acid (DHA), a major (n-3) fatty acid of the brain, ameliorates the impairment of learning ability in an animal model of Alzheimer's disease (AD), rats infused with amyloid-beta (Abeta) peptide (1-40) into the cerebral ventricle. Inbred 3rd generation male rats (20 wk old) fed a fish oil-deficient diet were randomly divided into 4 groups: a vehicle group, an Abeta peptide-infused group (Abeta group), a DHA group, and an Abeta + DHA group. A mini-osmotic pump filled with Abeta peptide or vehicle was implanted in the rats, and they were tested for learning ability-related reference and working memory in an 8-arm radial maze. The rats were then orally fed DHA dissolved in 5% gum Arabic solution at 300 mg/(kg . d) (DHA and Abeta + DHA groups) or vehicle alone (vehicle and Abeta groups) and tested again for learning ability. DHA administered for 12 wk significantly reduced the increase in the number of reference and working memory errors in the Abeta-infused rats, and increased both the cortico-hippocampal level of DHA and the molar ratio of DHA/arachidonic acid, suggesting an amelioration of the impaired spatial cognition learning ability. Furthermore, DHA suppressed the increases in the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and the hippocampus of Abeta-infused rats, suggesting that DHA increases antioxidative defenses. DHA is thus a possible therapeutic agent for ameliorating learning deficiencies due to Alzheimer's disease.
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DHA attenuates lipid peroxides and reactive oxygen species in the cerebral cortex and the hippocampus of Aβ-infused rats.
“DHA attenuates lipid peroxides and reactive oxygen species in the cerebral cortex and the hippocampus of Aβ-infused rats, suggesting that DHA elicits neuroprotection by blocking Aβ40/Aβ42 neurotoxicity (Calon et al., 2004; Hashimoto et al., 2005)”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Hashimoto et al., 2005
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- Authors
- Hashimoto, M., Tanabe, Y., Fujii, Y., Kikuta, T., Shibata, H., & Shido, O.
- Affiliations
- Shimane University (JP)
- Corresponding author
- Hashimoto, Michio
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 135
- Issue
- 3
- Pages
- 549-555
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2111757144
- Cited by
- 288
- References
- 46
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 10 · 2020: 10 · 2019: 10 · 2018: 12 · 2017: 7 · 2016: 20 · 2015: 25 · 2014: 18 · 2013: 13 · 2012: 17
- FWCI
- 18.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- docosahexaenoic acid, Alzheimer's disease, amyloid-beta, spatial learning, memory impairment, omega-3 fatty acids, hippocampus, cerebral cortex, oxidative stress, lipid hydroperoxides, antioxidant defense, reference memory, working memory, 8-arm radial maze
- MeSH terms
- Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Docosahexaenoic Acids, Learning, Space Perception, Amyloid beta-Peptides, Rats, Wistar, Reactive Oxygen Species, Rats
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