title: Fish oil improves learning impairments of diabetic rats by blocking PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways.
abstract: Previous research has demonstrated that diabetes induces learning and memory deficits. However, the mechanism of memory impairment induced by diabetes is poorly understood. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown to enhance learning and memory and prevent memory deficits in various experimental conditions. The present study investigated the effects of fish oil supplementation on the lipid peroxidation, inflammation and neuron apoptosis in the hippocampus of streptozotocin (STZ)-induced diabetes rats. The effects of diabetes and fish oil treatment on the spatial learning and memory were also evaluated using the Morris Water Maze. STZ-induced diabetes impaired spatial learning and memory of rats, which was associated with the inflammation, oxidative stress and apoptosis of hippocampal neurons. Fish oil administration ameliorated cognitive deficit, reduced oxidative stress and tumor necrosis factor α (TNF-α), protected the hippocampal neurons by increasing Protein Kinase B (AKT) phosphorylation and decreasing caspase-9 expression. These results suggested that the principle mechanisms involved in the antidiabetic and neuroprotective effect of fish oil were its antioxidant, anti-inflammatory and anti-apoptosis potential, supporting a potential role for fish oil as an adjuvant therapy for the prevention and treatment of diabetic complications.
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: D
authors.initials: D
authors.lastname: Jia
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: L-J
authors.initials: LJ
authors.lastname: Heng
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: fmmur.young@gmail.com.
authors.forename: R-H
authors.initials: RH
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, PR China. Electronic address: ggaoguodong@gmail.com.
authors.forename: G-D
authors.initials: GD
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D005395:Fish Oils / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
chemical_list: D005395:Fish Oils; D016328:NF-kappa B; D018697:Nootropic Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C506435:Casp9 protein, rat; D053453:Caspase 9
keywords: AKT; ANOVA; DHA; DM; EDTA; ELISA; EPA; FO; IKKβ; IKKβ/NF-κB; IL-1β; IκB kinase β; MDA; NF-κB; PCR; PI3K; PUFAs; Protein Kinase B (PKB); SDS; SOD; STZ; TNF-α; analysis of variance; cognitive impairments; diabetes; diabetes mellitus; docosahexaenoic acid; eicosapentaenoic acid; enzyme-linked immunosorbent assay; ethylenediaminetetraacetic acid; fish oil; inflammation; interleukin-1β; lipid peroxidation; malondialdehyde; nuclear factor-κB; phosphoinositide 3-kinase; polymerase chain reaction; polyunsaturated fatty acids; sodium dodecyl sulfate; streptozotocin; superoxide dismutase; tumor necrosis factor α