慢性新治疗代理改进内存管理的阿尔茨海默病小鼠模型τ沉积。

阿尔茨海默病(AD)的临床特征是进步的认知能力下降,最终导致死亡,通常在10年内诊断。据估计,目前全世界有超过1800万人的广告,和影响个体的数量到2025年预计将翻一番。异常τhyperphosphorylation及其积累到intra-neuronal神经原纤维缠结与阿尔茨海默氏症的神经退化疾病和tauopathies相似。一个策略来减少τ积累可以通过药物治疗学。本研究的目的是测试一种慢性的影响政府的新治疗小鼠模型的代理τ沉积(Tg4510老鼠)影响大脑的认知障碍和τ病理学。Tg4510老鼠,带着转基因对人类four-repeatτ与P301L突变(4 r0n tauP301L)以及转基因钙/ calmodulin-dependent蛋白激酶II型(CAMK-II)四环素控制反式激活因子的蛋白质。人类P301L突变导致常染色体继承居多的痴呆称为额颞叶痴呆和帕金森症与17号染色体(FTDP-17)。老鼠(Tg4510;n = 12 /组,平衡对性别和垃圾)收到测试代理或控制(车辆)到啮齿动物食物的饮食治疗口腔交付期间3个月。一群12未经处理的非转基因小鼠(FVB / 129年代F1杂交背景)是用来测量基线行为表现和胶质激活测量。 All animals were 3 months old at the start of the study. Mice were maintained on a twelve-hour light/dark cycle. Water and food were provided ad libitum throughout the experiment. 2 weeks before the termination of the study, the mice were subjected to behavioral testing including open field, Y maze, radial arm water maze (RAWM) and novel object recognition by an observer blind to the treatment/genotype of the mice in order to evaluate learning, memory and general activity. Mice were euthanized with Somnasol®. Blood was drawn by cardiac puncture. Brains were collected following transcardial perfusion with 0.9% normal saline solution. Brains were sectioned with a freezing microtome and free-floating sections were stained for various molecular forms of tau. Differences between treatment conditions were assessed statistically using two-way ANOVA or student t-test when appropriate, with StatView version 5.0 (SAS institute Inc, Cary NC).

Tg4510老鼠的饮食包含测试代理显示显著改善学习和记忆在摇臂水迷宫因为他们相比大大减少错误Tg4510控制饮食。如前所述,一个基因型效应体现在空旷的田野,rotarod和新奇物体的识别,但是没有治疗效果。包含测试代理的饮食没有影响大脑体重或体重。初步数据似乎表明没有区别在τ病理学评估免疫印迹和免疫组织化学。慢性管理测试代理Tg4510小鼠诱导显著改善摇臂水迷宫期间在学习和记忆中与τ寡聚物的减少海马匀浆。没有影响的观察饮食等行为测试开放的领域,rotarod和小说对象识别。饮食没有影响大脑重量和体重。