title: Protective effects of prescription n-3 fatty acids against impairment of spatial cognitive learning ability in amyloid β-infused rats.
abstract: Deposition of amyloid β peptide (Aβ) into the brain causes cognitive impairment. We investigated whether prescription pre-administration of n-3 fatty acids improves cognitive learning ability in young rats and whether it protects against learning ability impairments in an animal model of Alzheimer's disease that was prepared by infusion of Aβ(1-40) into the cerebral ventricles of rats. Pre-administration of TAK-085 (highly purified and concentrated n-3 fatty acids containing eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester) at 300 mg kg(-1) day(-1) for 12 weeks significantly reduced the number of reference memory errors in an 8-arm radial maze, suggesting that long-term administration of TAK-085 improves cognitive leaning ability in rats. After pre-administration, the control group was divided into the vehicle and Aβ-infused groups, whereas the TAK-085 pre-administration group was divided into the TAK-085 and TAK-085 + Aβ groups (TAK-085-pre-administered Aβ-infused rats). Aβ(1-40) or vehicle was infused into the cerebral ventricle using a mini osmotic pump. Pre-administration of TAK-085 to the Aβ-infused rats significantly suppressed the number of reference and working memory errors and decreased the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and hippocampus of Aβ-infused rats, suggesting that TAK-085 increases antioxidative defenses. The present study suggests that long-term administration of TAK-085 is a possible therapeutic agent for protecting against Alzheimer's disease-induced learning deficiencies.
authors: Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumo, Shimane, 693-8501, Japan. michio1@med.shimane-u.ac.jp
authors: Michio
authors: M
authors: Hashimoto
authors: Ryuichi
authors: R
authors: Tozawa
authors: Masanori
authors: M
authors: Katakura
authors: Hossain
authors: H
authors: Shahdat
authors: Abdul Md
authors: AM
authors: Haque
authors: Yoko
authors: Y
authors: Tanabe
authors: Shuji
authors: S
authors: Gamoh
authors: Osamu
authors: O
authors: Shido
mesh_terms: D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D005227:Fatty Acids / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D008054:Lipid Peroxides / Q000032:analysis; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D016229:Amyloid beta-Peptides; D004338:Drug Combinations; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; C587319:TAK-085; D004281:Docosahexaenoic Acids; C035276:eicosapentaenoic acid ethyl ester; C067518:4,7,10,13,16,19-docosahexaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid