INHIBITORY ACTION OF （-） CLAUSENAMIDE ON HYPERPHOSPHORYLATION OF TAU PROTEIN IN EXPERIMENTAL DIABETIC MICE

作     者：Yong CHENG Jun-Tian ZHANG Department of Pharmacology, Institute of Material Medica, Peking Union Medical college & Chinese Academy of Medical Sciences, Beijing 100050, China 

会议名称：《2004 National Meeting on Pharmacology of Young Pharmacologists》

会议日期：2004年

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

关 键 词：Alzheimer’s disease (-)clausenamide tau protein hyperphosphorylation microtubule 

摘      要：正 AIMS: Neurofibrillary tangles （NFTS） are histopathological lesions in Alzheimer’s disease（AD）. The core component of PHFs, which make up NFTs, results from abnormalhyperphosphorylated of microtubule-associated protein tau. The microtubule stabilizingfunction of tau is greatly diminished by its hyperphosphorylation to PHF-tau, which bindspoorly to tubulin and leads to cytoskeletal loss and cell death. The diabetes mice which wereinduced by streptozotocin （STZ）, the insulin-secreting β-cell killer, appeared tau proteinhyperphosphorylation at Ser 199/202 sites in the central nervous system. （-） Clausenamide, anew compound isolated from clausena lausium （lour） skeel, which showed neuroprotectiveeffects in the central nervous system in previous studies. The Aim in present study is todetect the effects of （-） clausenamide on inhibiting tau protein hyperphosphorylation in theseexperimental diabetic ***: The mice were injected STZ at 200 mg/kg, once, i.p. The successful diabeticmodels were divided into model （DM） group, （-） clausenamide 7.5、15、30mg/kg groups, andthe mice untreated with STZ as control group. The Morris water maze and step-through testwere performed at 7 weeks after STZ was given. After behavior assays, mice were *** in neuron of CA1 of hippocampus were detected by electron microscope andimmunohistochemistry was performed with AT-8、tau-1、GSK-3、CDK-5、PP-1 and ***: The diabetic mice showed neuropathological lesions such as impaired ability oflearning and memory, hyperphosphorylation of tau protein at Ser199/202 sites, fragmentationand dissolution of microtubules, the expression of kinases （GSK-3 and CDK-5） increasingand phosphatase （PP-1） decreasing in hippocampal neuron. While in the mice which hadreceived （-） clausenamide, the microtubule structure showed morphology improvement at7.5-15mg/kg, morphology was almost normal at 30mg/kg. In immunohistochemistry fortubulin antibody, there was also gradual increase i