Effects Of Recombinant Human NAMPT Intravenous Injection On Physiological/biochemical Indexes And Brain Structure Of Normal Mice

Objective:To observe the effect of plasma nicotinamide phosphoribosyltranserase (NAMPT) multiple intravenous injection on physiological/biochemical indexes and brain structure of normal mice.Methods:Plasma NAMPT was increased by intravenous injection of wild type human recombinant NAMPT (1,3and10μg/kg) or H247A mutant NAMPT(with very weak enzymatic activity) once every3days and totally for32days. Then, the change of body weight, blood pressure, heart rate, serum glucose, serum total cholesterol and triglyceride were determined, and the morphology of neuron, astrocyte and microglia in hippocampus was detected.Result:The injection of both NAMPT had no significant effect on body weight, blood pressure, heart rate, blood glucose, total cholesterol and triglyceride. The injection of two kinds of NAMPT protein also did not affect the morphology of neuron, astrocyte and microglia in hipppocampus.Conclusion:The elevation of plasma NAMPT had no influence on physiological/biochemical indexes of normal mice as well as the morphology of neuron, astrocyte and microglia in normal mice brain, which implies that the elevation of plasma NAMPT may not induce metabolic and neuronal dysfunction in normal individual. The independently risk for such dysfunction induced by elevated serum NAMPT could be low. Objective:To observe the role of NAMPT on neurological behavior performance, and to explore the underlined mechanisms.Methods:by using icv, FK866(10-7M,3×10-7M,5×10-7M, total volume10μl) or lentivirus carried NAMPT shRNA/NAMPT full length was administrated to inhibit the enzymatic of NAMPT or to down expression/over-expression NAMPT. The behavioral change (open field, learning and memory), the morphology change (neuron, astrocyte and microglia in hippocampus and cortex), and the biochemical change (expression of GFAP, cytokines, transporters and NAD) was observed.Results:The administration of FK866dose-dependently decreased the activity of mice in open field, and decreased the exploration to the center region in open field. The administration of FK866did not affect the density and morphology of neuron and microglia. However, using immunofluoroscence staining, we found that FK866significantly increased the density of astrocyte in the hippocampus of mice but not in the cortex. Using western blot and immunofluoroscence staining, we found that FK866significantly and dose-dependently increased GFAP expression.The other studies are still on going.Conclusion:NAMPT could be involved in the neurological behavior performance of mice through regulation the cross-talk between neuron and astrocyte.