title: Prescription n-3 fatty acids, but not eicosapentaenoic acid alone, improve reference memory-related learning ability by increasing brain-derived neurotrophic factor levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.
abstract: Metabolic syndrome is implicated in the decline of cognitive ability. We investigated whether the prescription n-3 fatty acid administration improves cognitive learning ability in SHR.Cg-Lepr(cp)/NDmcr (SHR-cp) rats, a metabolic syndrome model, in comparison with administration of eicosapentaenoic acid (EPA, C20:5, n-3) alone. Administration of TAK-085 [highly purified and concentrated n-3 fatty acid formulation containing EPA ethyl ester and docosahexaenoic acid (DHA, C22:6, n-3) ethyl ester] at 300 mg/kg body weight per day for 13 weeks reduced the number of reference memory-related errors in SHR-cp rats, but EPA alone had no effect, suggesting that long-term TAK-085 administration improves cognitive learning ability in a rat model of metabolic syndrome. However, the working memory-related errors were not affected in either of the rat groups. TAK-085 and EPA administration increased plasma EPA and DHA levels of SHR-cp rats, associating with an increase in EPA and DHA in the cerebral cortex. The TAK-085 administration decreased the lipid peroxide levels and reactive oxygen species in the cerebral cortex and hippocampus of SHR-cp rats, suggesting that TAK-085 increases antioxidative defenses. Its administration also increased the brain-derived neurotrophic factor levels in the cortical and hippocampal tissues of TAK-085-administered rats. The present study suggests that long-term TAK-085 administration is a possible therapeutic strategy for protecting against metabolic syndrome-induced learning decline.
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: Takayuki
authors: T
authors: Inoue
authors: Masanori
authors: M
authors: Katakura
authors: Yoko
authors: Y
authors: Tanabe
authors: Shahdat
authors: S
authors: Hossain
authors: Satoru
authors: S
authors: Tsuchikura
authors: Osamu
authors: O
authors: Shido
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000097:blood / Q000627:therapeutic use*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005227:Fatty Acids / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D024821:Metabolic Syndrome / Q000188:drug therapy*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004338:Drug Combinations; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D008054:Lipid Peroxides; C587319:TAK-085; D004281:Docosahexaenoic Acids; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid
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