title: Effect of docosahexaenoic acid on hippocampal neurons in high-glucose condition: involvement of PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways.
abstract: Accumulating evidence suggested that hyperglycemia played a critical role in hippocampus dysfunction in patients with diabetes mellitus. However, the multifactorial pathogenesis of hyperglycemia-induced impairments of hippocampal neurons has not been fully elucidated. Docosahexaenoic acid (DHA) has been shown to enhance learning and memory and affect neural function in various experimental conditions. The present study investigated the effects of DHA on the lipid peroxidation, the level of inflammatory cytokines and neuron apoptosis in the hippocampal neurons in high-glucose condition. High-glucose administration increased the level of tumor necrosis factor α (TNF-α) and IL-6, induced oxidative stress and apoptosis of hippocampal neurons in vitro. DHA treatment reduced oxidative stress and TNF-α expression, protected the hippocampal neurons by increasing AKT phosphorylation and decreasing caspase-3 and caspase-9 expression. These results suggested that high-glucose exposure induced injury of hippocampal neurons in vitro, and the principle mechanisms involved in the neuroprotective effect of DHA were its antioxidant and anti-apoptotic potential. DHA may thus be of use in preventing or treating neuron-degeneration resulting from hyperglycemia.
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab 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 Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: X-H
authors.initials: XH
authors.lastname: Hou
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: R
authors.initials: R
authors.lastname: Cao
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: F
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: H-Q
authors.initials: HQ
authors.lastname: Liu
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: A-L
authors.initials: AL
authors.lastname: Ji
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: X-N
authors.initials: XN
authors.lastname: Xu
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, The Ministry of Education Key Lab 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: nutrition@fmmu.edu.cn.
authors.forename: F
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology; D006943:Hyperglycemia / Q000188:drug therapy* / Q000276:immunology; D007328:Insulin / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000276:immunology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007328:Insulin; D015850:Interleukin-6; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D005947:Glucose
keywords: IKKβ/NF-κB; apoptosis; diabetes; docosahexaenoic acid; hippocampal neuron; lipid peroxidation