lignans and Learning-Disabilities

Topics: Animals; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p19; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Galactose; Gene Expression; Hippocampus; Humans; Learning Disabilities; Lignans; Male; Memory; Memory Disorders; Mice; Mice, Inbred ICR; Retinoblastoma Protein; rho GTP-Binding Proteins; Schisandra; Tumor Suppressor Protein p53

To observe the effects of schizandrins on the learning and memory disorder in mice, and explore its mechanism.. The memory impairment model was established by using the pentobarbital sodium (20 mg x kg(-1)) intraperitoneally injected in mice. Schizandrins (0.5, 1.0, 2.0 g x kg(-1)) were administered through intragavage for consecutive 14 days. Morris Water Maze test was used to evaluate the impairment of learning and memory. The energy of superoxide dismutase (SOD), nitric oxide (NO) and catalase (CAT) of brain tissue were measured. And the positive expression of nuclear transcription factor-kappaB p65 (NF-kappaB p65), caspase-3 in the hippocampus CA1 region were determined by immunohistochemical analysis. At the cellular level, 24 h after schizandrins (0.062 5, 0.125, 0.25 g x L(-1)) were pre-administered, the apoptosis model of PC12 cell was induced by H2O2, and activity of PC12 cell was detected by MTT colorimetric assay, the energy of NO in cell serum were measured. The expression of Bcl-2 was determined by the combination of immunocytochemical staining and image analysis software.. Morris Water Maze test showed that the model group mice took shorter searching time and distance on the previous flat area than those in the control group (P < 0.05), which could be prolonged after schizandrins treatment (P < 0.05, P < 0.01). Compared with the control group, the level of NO increased while the activity of SOD, CAT decreased in the model group (both P < 0.01). After treated with schizandrins, the level of NO significantly decreased (P < 0.01), while the activity of SOD increased (P < 0.01). Immunohistochemistry analysis showed that the protein expression of NF-kappaB p65, Caspase-3 in the hippocampal CA1 region significantly increased after modeling, while schizandrins (1.0 g x kg(-1)) can significantly inhibit the protein expression of NF-kappaB p65, Caspase-3 (P < 0.05, P < 0.01). Compared with the H2O2, model group, schizandrins (0.125, 0.25 g x L(-1)) can significantly increased PC12 cell activity and decreased the NO level (P < 0.05, P < 0.01), the expression of Bcl-2 in the schizandrins group (0.125, 0.25 g x L(-1)) was up-regulated.. Schizandrins could improve the learning-memory dysfunction induced by the sodium pentobarbital in mice, and its protective mechanism is related to the lowering oxidative damage and inhibiting the cell apoptosis through up-regulating the expression of Bcl-2.

Topics: Animals; Apoptosis; Behavior, Animal; CA1 Region, Hippocampal; Caspase 3; Cell Line; Cyclooctanes; Disease Models, Animal; Drugs, Chinese Herbal; Female; Learning Disabilities; Lignans; Male; Memory Disorders; Mice; Nitric Oxide; Oxidative Stress; PC12 Cells; Polycyclic Compounds; Proto-Oncogene Proteins c-bcl-2; Rats; Superoxide Dismutase; Transcription Factor RelA

Previous studies have shown that macelignan has anti-inflammatory and neuroprotective effects. Subsequently, in the current study, we demonstrate that oral administrations of macelignan reduce the hippocampal microglial activation induced by chronic infusions of lipopolysaccharide (LPS) into the fourth ventricle of Fisher-344 rat brains. A Morris water maze was used to evaluate the status of the hippocampal-dependent spatial learning in control rats with an artificial cerebrospinal fluid infusion, rats with chronic LPS infusions, and rats with chronic LPS infusions and oral administrations of macelignan. The rats with chronic LPS infusions showed spatial memory impairments relative to the control rats in the performance of the memory task. Daily administration of macelignan reduced the spatial memory impairments induced by the chronic LPS infusions. The results indicate that macelignan may possess therapeutic potential for the prevention of Alzheimer's disease.

Topics: Analysis of Variance; Animals; Avoidance Learning; Behavior, Animal; Histocompatibility Antigens Class II; Inflammation; Learning Disabilities; Lignans; Lipopolysaccharides; Male; Maze Learning; Microglia; Rats; Rats, Inbred F344; Reaction Time; Space Perception