Cited by 288Fatty Acid Research and HealthAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 44 of the 46 references it cites were found in a registry or an index.

Chronic Administration of Docosahexaenoic Acid Ameliorates the Impairment of Spatial Cognition Learning Ability in Amyloid β–Infused Rats

Open access

Hashimoto, Michio, Tanabe, Yoko, Fujii, Yoshimi, Kikuta, Toshihiko, Shibata, Hitoshi, Shido, Osamu·2005·The Journal of Nutrition

DOI 10.1093/jn/135.3.549

Open this paper in CoChat — free account Open PDF

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1093/jn/135.3.549

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 316,394
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585
Direct transesterification of all classes of lipids in a one-step reaction.
Lepage, G., & ROY, C. C. (1986) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38861-1 · Cited by 2,385
Consumption of Fish and n-3 Fatty Acids and Risk of Incident Alzheimer Disease
Morris, M. C., Evans, D. A., Bienias, J. L., Tangney, C. C., Bennett, D. A., Wilson, R. S., Aggarwal, N., & Schneider, J. (2003) · Archives of Neurology · doi:10.1001/archneur.60.7.940 · Cited by 1,135
Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys.
Neuringer, M. D., CONNOR, W. E., Lin, D. S., Barstad, L., & Luck, S. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.11.4021 · Cited by 914
Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease
Söderberg, M., Edlund, C., Kristensson, K., & Dallner, G. (1991) · Lipids · doi:10.1007/bf02536067 · Cited by 667
Essential Fatty Acids and the Brain
Haag, M. (2003) · The Canadian Journal of Psychiatry · doi:10.1177/070674370304800308 · Cited by 421
Effect of dietary alpha-linolenate/linoleate balance on brain lipid compositions and learning ability of rats.
Yamamoto, N., Saitoh, M., Moriuchi, A., Nomura, M., & Okuyama, H. (1987) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38713-7 · Cited by 383
Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats
Hashimoto, M., Hossain, S., Shimada, T., Sugioka, K., Yamasaki, H., Fujii, Y., Ishibashi, Y., Oka, J., & Shido, O. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00905.x · Cited by 364
The role of n-3 polyunsaturated fatty acids in brain: Modulation of rat brain gene expression by dietary n-3 fatty acids
Kitajka, K., Puskás, L. G., Zvara, Á., Hackler, L., Barceló‐Coblijn, G., Yeo, Y. K., & Farkas, T. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042698699 · Cited by 328
Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats
Gamoh, S., Hashimoto, M., Sugioka, K., Hossain, S., Hata, N., Misawa, Y., & Masumura, S. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00107-4 · Cited by 307
Molecular genetics of Alzheimer’s disease
George‐Hyslop, P. S. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00301-7 · Cited by 281
Protective effects of idebenone and α‐tocopherol on β‐amyloid‐(1–42)‐induced learning and memory deficits in rats: implication of oxidative stress in β‐amyloid‐induced neurotoxicity in vivo
Yamada, K., Tanaka, T., Han, D., Senzaki, K., Kameyama, T., & Nabeshima, T. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00408.x · Cited by 238
Generation of Aggregated β-Amyloid in the Rat Hippocampus Impairs Synaptic Transmission and Plasticity and Causes Memory Deficits
Stéphan, A., Laroche, S., & Davis, S. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-15-05703.2001 · Cited by 228
Age-related changes in synaptic function: analysis of the effect of dietary supplementation with ω-3 fatty acids
McGahon, B., Martin, D. S. D., Horrobin, D. F., & Lynch, M. A. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00219-5 · Cited by 225
Chronic Administration Of Docosahexaenoic Acid Improves The Performance Of Radial Arm Maze Task In Aged Rats
Gamoh, S., Hashimoto, M., Hossain, S., & Masumura, S. (2001) · Clinical and Experimental Pharmacology and Physiology · doi:10.1046/j.1440-1681.2001.03437.x · Cited by 213
Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus
Puskás, L. G., Kitajka, K., Nyakas, C. J., Barceló‐Coblijn, G., & Farkas, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0337683100 · Cited by 176
Modification by docosahexaenoic acid of age-induced alterations in gene expression and molecular composition of rat brain phospholipids
Barceló‐Coblijn, G., Hőgyes, E., Kitajka, K., Puskás, L. G., Zvara, Á., Hackler, L., Nyakas, C. J., Penke, Z., & Farkas, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1734008100 · Cited by 166
Continuous Infusion of .BETA.-Amyloid Protein into the Rat Cerebral Ventricle Induces Learning Impairment and Neuronal and Morphological Degeneration.
Nitta, A., Fukuta, T., Hasegawa, T., & Nabeshima, T. (1997) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.73.51 · Cited by 142
Dietary Docosahexaenoic Acid Increases Cerebral Acetylcholine Levels and Improves Passive Avoidance Performance in Stroke-Prone Spontaneously Hypertensive Rats
Minami, M., Kimura, S., Endo, T., Hamaue, N., Hirafuji, M., Togashi, H., Matsumoto, M., Yoshioka, M., Saito, H., Watanabe, S., et al. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(97)00300-6 · Cited by 140
Cholesterol Modulates the Membrane- Disordering Effects of Beta-Amyloid Peptides in the Hippocampus: Specific Changes in Alzheimer’s Disease
Eckert, G. P., Cairns, N. J., Maras, A., Gattaz, W. F., & Müller, W. E. G. (2000) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017234 · Cited by 137
Antioxidative Effects of Docosahexaenoic Acid in the Cerebrum Versus Cerebellum and Brainstem of Aged Hypercholesterolemic Rats
Hossain, S., Hashimoto, M., Gamoh, S., & Masumura, S. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0721133.x · Cited by 134
Evidence for the Involvement of Docosahexaenoic Acid in Cholinergic Stimulated Signal Transduction at the Synapse
Jones, C. R., Arai, T., & Rapoport, S. I. (1997) · Neurochemical Research · doi:10.1023/a:1027341707837 · Cited by 119
The Antioxidant Vitamin E Modulates Amyloid β-Peptide-Induced Creatine Kinase Activity Inhibition and Increased Protein Oxidation: Implications for the Free Radical Hypothesis of Alzheimer's Disease
Yatin, S. M., Aksenov, M. Y., & Butterfield, D. A. (1999) · Neurochemical Research · doi:10.1023/a:1020997903147 · Cited by 112
Social environment alters both ontogeny of dopamine innervation of the medial prefrontal cortex and maturation of working memory in gerbils (Meriones unguiculatus)
Winterfeld, K. T., Teuchert, G., & Dawirs, R. R. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19980415)52:2 · Cited by 110
Docosahexaenoic acid improves long‐term potentiation attenuated by phospholipase A2 inhibitor in rat hippocampal slices
Fujita, S., Ikegaya, Y., Nishikawa, M., Nishiyama, N., & Matsuki, N. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703970 · Cited by 109
DHA-enriched phospholipid diets modulate age-related alterations in rat hippocampus
Favrelière, S., Perault, M. C., Huguet, F., de Javel, D., Bertrand, N., Piriou, A., & Durand, G. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00064-7 · Cited by 107
Docosahexaenoic acid supplementation improves the moderately severe dementia from thrombotic cerebrovascular diseases
Terano, T., Fujishiro, S., Ban, T., Yamamoto, K., Tanaka, T., Noguchi, Y., Tamura, Y., Yazawa, K., & Hirayama, T. (1999) · Lipids · doi:10.1007/bf02562338 · Cited by 105
The chronic administration of docosahexaenoic acid reduces the spatial cognitive deficit following transient forebrain ischemia in rats
Okada, M., Amamoto, T., Tomonaga, M., Kawachi, A., Yazawa, K., Mine, K., & Fujiwara, M. (1996) · Neuroscience · doi:10.1016/0306-4522(95)00427-0 · Cited by 101
Oxidative Injury of Synapse and Alteration of Antioxidative Defense Systems in Rats, and Its Prevention by Vitamin E
Urano, S., Asai, Y., Makabe, S., Matsuo, M., Izumiyama, N., OHTSUBO, K., & Endō, T. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00064.x · Cited by 96
The Hypotensive Effect of Docosahexaenoic Acid Is Associated with the Enhanced Release of ATP from the Caudal Artery of Aged Rats
Hashimoto, M., Shinozuka, K., Gamoh, S., Tanabe, Y., Hossain, S., Kwon, Y. M., Hata, N., Misawa, Y., Kunitomo, M., & Masumura, S. (1999) · Journal of Nutrition · doi:10.1093/jn/129.1.70 · Cited by 91
Amyloid β Protein (Aβ) Starts to Deposit As Plasma Membrane-Bound Form in Diffuse Plaques of Brains from Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type, Alzheimer Disease and Nondemented Aged Subjects
Yamaguchi, H., Maat–Schieman, M. L. C., van Duinen, S. G., Prins, F. A., Neeskens, P., Natté, R., & Roos, R. A. C. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.8.723 · Cited by 91
Changes in antioxidant enzymes activities, aggregability and malonyldialdehyde concentration in blood platelets from patients with coronary heart disease
Buczyński, A., Wachowicz, B., Kędziora–Kornatowska, K., Tkaczewski, W., & Kȩdziora, J. (1993) · Atherosclerosis · doi:10.1016/0021-9150(93)90208-c · Cited by 87
Differential effects of dietary fish oil on myocardial prostaglandin I2 and thromboxane A2 production
Abeywardena, M. Y., McLennan, P. L., & Charnock, J. S. (1991) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1991.260.2.h379 · Cited by 71
Chronic dietary n‐3 polyunsaturated fatty acids deficiency affects the fatty acid composition of plasmenylethanolamine and phosphatidylethanolamine differently in rat frontal cortex, striatum, and cerebellum
Favrelière, S., Barrier, L., Durand, G., Chalon, S., & Tallineau, C. (1998) · Lipids · doi:10.1007/s11745-998-0221-y · Cited by 67
Influence of docosahexaenoic acid on cerebral lipid peroxide level in aged rats with and without hypercholesterolemia
Hossain, S., Hashimoto, M., & Masumura, S. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00147-5 · Cited by 65
Docosahexaenoic acid–A new therapeutic approach to peroxisomal‐disorder patients
Martínez, M., Pineda, M., Vidal, R., Conill, J., & Martin, B. (1993) · Neurology · doi:10.1212/wnl.43.7.1389 · Cited by 64
Effects of docosahexaenoic acid on annular lipid fluidity of the rat bile canalicular plasma membrane
Hashimoto, M., Hossain, S., Shimada, T., Yamasaki, H., Fujii, Y., & Shido, O. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31607-2 · Cited by 56
Fish Consumption and the Risk of Alzheimer Disease
Friedland, R. P. (2003) · Archives of Neurology · doi:10.1001/archneur.60.7.923 · Cited by 53
Distinctive inhibitory activity of docosahexaenoic acid against sphingosine-induced apoptosis
Kishida, E., Yano, M., Kasahara, M., & Masuzawa, Y. (1998) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/s0005-2760(98)00015-0 · Cited by 49
Effect of DHA Oil Supplementation on Intelligence and Visual Acuity in the Elderly
Suzuki, H., Morikawa, Y., & Takahashi, H. (2000) · KARGER eBooks · doi:10.1159/000059767 · Cited by 46
Continuous Infusion of β-Amyloid Protein into the Rat Cerebral Ventricle Induces Learning Impairment and Neuronal and Morphological Degeneration
Nitta, A., Fukuta, T., Hasegawa, T., & Nabeshima, T. (1997) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.60.51 · Cited by 40
Synaptic plasma membrane-bound acetylcholinesterase activity is not affected by docosahexaenoic acid-induced decrease in membrane order
Shahdat, H., Hashimoto, M., Shimada, T., & Shido, O. (2004) · Life Sciences · doi:10.1016/j.lfs.2003.10.028 · Cited by 25

Research works printed but not linked: 3

Miyanaga, 1995, Clinical effects of DHA in demented patients, J. Clin. Ther. Med., 11, 881
Kotchabhakdi, 2003, Effects of different dosages of docosahexaenoic acid (DHA) intake on maze-learning ability and dendritic spines in rats, Soc. Neurosci. Abstracts Program No. 941.17.
Lim, 2003, Diets enriched with polyunsaturated DHA (docosahexaenoic acid) can lower amyloid levels and plaque burden in an Alzheimer’s disease mouse model, Soc. Neurosci. Abstracts Program No. 201.25.

Sorted by citations

Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942
Brain foods: The effects of nutrients on brain function.
Gómez-Pinilla, F. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2421 · Cited by 1,372
A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease
Lukiw, W. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25420 · Cited by 897
Essential Fatty Acids: Biochemistry, Physiology and Pathology
Das, U. N. (2006) · Biotechnology Journal · doi:10.1002/biot.200600012 · Cited by 650
Alpha-linolenic acid and its conversion to longer chain n−3 fatty acids: Benefits for human health and a role in maintaining tissue n−3 fatty acid levels
Barceló‐Coblijn, G., & Murphy, E. J. (2009) · Progress in Lipid Research · doi:10.1016/j.plipres.2009.07.002 · Cited by 605

See all 288

Authors: Hashimoto, M., Tanabe, Y., Fujii, Y., Kikuta, T., Shibata, H., & Shido, O.
Affiliations: Shimane University (JP)
Corresponding author: Hashimoto, Michio
ORCID: Hashimoto, Michio
Tanabe, Yoko
Venue: The Journal of Nutrition
Publisher: Elsevier BV
Published: 2005-03
Volume: 135
Issue: 3
Pages: 549-555
ISSN: 0022-3166 (ISSN-L)
DOI: 10.1093/jn/135.3.549
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6547 d)
Locations: Journal of Nutrition (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Chronic Administration of Docosahexaenoic Acid Ameliorates the Impairment of Spatial Cognition Learning Ability in Amyloid β–Infused Rats

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks