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Development of animal models for Alzheimer's disease

阿尔茨海默病动物模型的开发

基本信息

批准号：
07557009
负责人：
NABESHIMA Toshitaka
金额：
$ 4.03万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

We have investigated to develop animal models for Alzheimer's disease (AD) by continuous infusion of beta-amyloid protein (Abeta) into the cerebral ventricle of rats. The results obtained during the aid are as follows :In rats continuously infused Abeta,1 impairments of learning and memory were observed.2 deposition, of Abeta and decrease of choline acetyltransferase activity were observed in the cerebral cortex and hippocampus which play key roles in learning and memory.3 expression of glial fibrillary acidic protein, an index of gliosis, was increased in the hippocampus.4 ciliary neurotrophic factor content was increased in the cerebral cortex and hippocampus.5 nicotine- or high-K-evoked release of acetylcholine and dopamine in the cortex/hippocampus and striatum, respectively, was decreased.6 less electrophysiologicalresponse against nicotine in the hippocampal CAl pyramidal cells was observed.7 disability on induction of long-term potentiation in the hippocampal CAl pyramidal cells was observed.8 decrease of nicotine-induced enhancement of paired-pulse facilitation in the hippocampal CAl pyramidal cells was observed.9 administration of cognitive enhancers such as nefiracetam, propentofylline, arginine-vasopressin derivatives, idebenone and alpha-tocopherol, improves impairments of learning and memory induced by Abeta infusion.These results suggest that continuous infusion of Abeta is a good method to prepare the animal model of AD,which exhibits similar features observed in human AD patients. Moreover, this model is useful to evaluate the novel compounds for treatment of AD.

我们通过向大鼠脑室持续输注β -淀粉样蛋白（Abeta）来研究建立阿尔茨海默病（AD）动物模型。实验结果如下：连续输注β后，大鼠的学习记忆功能出现了明显的损伤。在学习和记忆中起关键作用的大脑皮层和海马区，观察到β - 2沉积和胆碱乙酰转移酶活性降低。3 .海马胶质纤维化指标胶质原纤维酸性蛋白表达增加。4 .大脑皮层和海马睫状体神经营养因子含量升高。5尼古丁或高钾诱发的乙酰胆碱和多巴胺在皮质/海马和纹状体的释放分别减少。海马锥体细胞对尼古丁的电生理反应减弱。观察海马CAl锥体细胞长期增强诱导的失能。8观察到尼古丁诱导的海马CAl锥体细胞配对脉冲促进的增强减弱。认知增强剂如奈非拉西坦、丙烯茶碱、精氨酸-抗利尿素衍生物、地地苯酮和α -生育酚可改善由β输注引起的学习和记忆障碍。这些结果表明，持续输注Abeta是一种制备AD动物模型的良好方法，该动物模型具有与人类AD患者相似的特征。此外，该模型可用于评估治疗AD的新化合物。