title: Long-term ginsenoside administration prevents memory loss in aged female C57BL/6J mice by modulating the redox status and up-regulating the plasticity-related proteins in hippocampus.
abstract: Memory impairment is considered to be one of the most prominent consequences of aging. Deterioration of memory begins in advance of old age in animals, including humans. The generation of reactive oxygen species (ROS) and/or free radicals-induced oxidative stress which is the major age-related changes, can lead to hippocampus damage and increase vulnerability to impaired learning and memory. Ginsenoside, the effective ingredient of ginseng, has been reported to have a neuron beneficial effect. In the present study, C57BL/6J mice aged 12 months were chronically treated with ginsenoside (three dose groups were given ginsenoside in drinking water for 8 months, the concentration of ginsenoside in drinking water was 0.028%, 0.056%, and 0.112% (w/v), respectively). Placebo-treated aged mice and young ones (4 months old) were used as controls. The efficacious effect of ginsenoside was manifested in the amelioration of memory impairment in aged mice by Morris water maze and step-down tests. Total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and thiobarbituric acid reactive substances (TBARS) have been used as the biomarkers of oxidative stress. In ginsenoside treated groups, the activities of T-SOD and GSH-Px markedly increased, and the levels of TBARS and the content of protein carbonyl decreased significantly in serum and in hippocampus. The activation of lipofuscin formation, disruption or loss of cristae in mitochondria, the irregular nucleus and condensed chromatin laid against the nuclear membrane in pyramidal cells of hippocampal CA1 region, which are all related to oxidative stress, were also reduced after ginsenoside treatment. Processes of memory formation and functional plasticity are associated with postsynaptic density-95 (PSD-95), protein kinase Cγ subunit (PKCγ) and brain derived neurotrophic factor (BDNF). In the present study, we found that long-term ginsenoside treatment prevented age-related reductions of PSD-95, PKCγ, and BDNF in the hippocampus. These results demonstrated that long-term ginsenoside administration may prevent memory loss in aged C57BL/6J mice by modulating the redox status and up-regulating the plasticity-related proteins in hippocampus.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China.
authors.forename: H F
authors.initials: HF
authors.lastname: Zhao
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Li
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002452:Cell Count; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D010084:Oxidation-Reduction / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011597:Psychomotor Performance / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D036145:Ginsenosides; D017392:Thiobarbituric Acid Reactive Substances; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C087857:protein kinase C gamma; D011493:Protein Kinase C