中国病理生理杂志2013，Vol.29Issue(3)：462-468,7.DOI:10.3969/j.issn.1000-4718.2013.03.014
侧脑室注射链脲佐菌素致大鼠脑内胰岛素通路障碍和认知水平降低
Intracerebroventricular injection of streptozotocin induces dysfunction of insulin signaling in brain and cognitive deficits in rats
杨文青 1马晶 1刘争 1芦永良 1余华荣1
作者信息
摘要
Abstract
AIM; To investigate the effect of insulin signaling on the development of Alzheimer disease (AD) and to explore its potential mechanisms. METHODS; The rats were treated with streptozotocin (STZ, 3 mg/kg) intrace-rebroventricularly (ICV) at the 1st day and the 3rd day of the experiment to induce dementia model. Twenty-one days after the injection of STZ at the 1st day, spatial learning and memory of the rats were determined by Morris water maze test. The expression levels of insulin-degrading enzyme (IDE), glycogen synthase kinase 3β (GSK-3β) , phosphorylated GSK-3β (p-GSK-3β) , tau and phosphorylated tau (p-tau) were measured by Western blotting. The levels of amyloid p-proteins ( Aβ1-40and Aβ1-42) in the brain of the rats were detected by the method of immunohistochemistry. The mRNA levels of insulin, insulin receptor, tau and IDE were measured by real-time RT-PCR. RESULTS: ICV-STZ deteriorated the abilities of spatial learning and memory of the rats and reduced the activity of IDE and the mRNA levels of insulin and insulin receptor. STZ treatment enhanced GSK-3p activity and tau phosphorylation. The levels of Aβ1-40 and Aβ1-42 in cerebral cortex were significantly increased in the rats treated with STZ. CONCLUSION: ICV-STZ results in AD-like behaviors and pathological changes via damaging the brain insulin signaling, indicating that insulin signaling may play important roles in the AD pathogenesis.关键词
阿尔茨海默病/胰岛素/淀粉样β蛋白/Tau蛋白质/胰岛素降解酶/糖原合成酶激酶3βKey words
Alzheimer disease/ Insulin/ Amyloid beta-protein/ Tau proteins/ Insulin-degrading enzyme/ Glycogen synthase kinase 3β分类
医药卫生引用本文复制引用
杨文青,马晶,刘争,芦永良,余华荣..侧脑室注射链脲佐菌素致大鼠脑内胰岛素通路障碍和认知水平降低[J].中国病理生理杂志,2013,29(3):462-468,7.
