Study On Hyperphosphorylation Of TAU Protein In Hippocampus Of Insulin-resistant Rats

Abjectives:Establishing insulin resistance rats model to observe the influentces of the fasting bloodglucose, insulin, insulin resistance on hyperphosphorylation of TAU protein in hippocampus, aswell as learning and memory,discussing the possible effect of insulin resistance in ADpathogenesis in order to provide a theoretical evidences for the early prevention and treatmentAlzheimer’s disease.Methods:301-month old healthy male Wistar rats, weighing120-150g, were randomly divided into threegroups, normal control group (NC)10, fed with normal diet; insulin resistance group (IR)10, givenhigh-sugar high-protein high-fat diet.Three months after the glucose oxidase in Rat Plasmaglucose values were measured by radioimmunoassay of plasma insulin, insulin resistanc index,compared with the normal group was statistically significant namely the model for success;Alzheimer’s disease group (AD)10,given high-sugar high-protein high-fat diet, after insulinresistance were injected streptozotocin(STZ) by stereotaxic method to intracerebroventricular; NCand IR group were given the same dose of citrate buffer intracerebroventricular injection.21dayspostoperative detection of rats behavior change, using Morris water maze test to detect thelearning and memory changes in rats; using the Morris water maze test, immunohistochemicaldetection pathological changes; Using Western blotting method analysis some phosphorylationlevel on tau protein (Ser199, Thr205, Thr212, Thr217, Ser396) were investigated. Results:1, the general research data of rats shows: Rats fasting blood glucose, insulin, plasma insulinresistance index IR, AD group was significantly higher than the normal control group (P <0.05),the difference was statistically significant which indicating that the model is successful.2, The results of rats’ learning and memory ability: Compared with NC group, Rats IR, AD groupsare significantly decreased in learning and memory ability, The time to escape from the watermaze was significantly prolonged (P <0.05). There is significant statistical meaning betweengroups (P <0.05).3, Hippocampal CA1region TAU immunohistochemical positive cells observed in the IR, the ADhippocampal CA1region more TAU immunoreactive cells, the cytoplasmic stain, brown color,while the NC group, cell staining lighter, the number of positive cellsless; compared with thecontrol group, the increase in the average gray value of cells, P <0.05, the difference wasstatistically significant.4, Rat hippocampal CA1Chief TAU and TAU phosphorylation by Western blot, showing that theNC group with a fine in the IR, the AD group. Using image analysis software for quantitativeanalysis of the imprinting, compared with the control group, NC gray value is significantly lower(P <0.05) the difference was statistically significant.Conclusion1, Injecting small doses of STZ into intracerebroventricular can simulate behavioral andpathological characteristics of AD, such as learning and memory impairment, the TAU proteinover-expression and so on. AD animal models were successfully established.2, Alzheimer-like disease in insulin resistance rats indicates that the failure insulin signal transduction may affect rats’ cognition, memory and other senior brain function.3, The increasing hyperphosphorylation expression in parts of the TAU protein in hippocampalCA1region indicating that the IR may be involved in adjusting TAU proteinhyperphosphorylation of the main component of neurofibrillary tangles, worsening ADpathological changes; IR may play an important role in alzheimer’s disease pathogenesis.