Senile Degeneration in the Brain of Octogon Degus

描述（由申请人提供）：阿尔茨海默病（AD）是最常见的神经退行性疾病，以进行性记忆丧失和大脑皮层大量细胞死亡为特征。阿尔茨海默病的主要原因是淀粉样蛋白的积累是导致神经变性的基本事件。对表达人类淀粉样蛋白前体蛋白（APP）和早老素家族突变的转基因小鼠的研究支持了这一假设。这些动物复制了该疾病的关键方面，包括淀粉样斑块、认知任务缺陷和负责学习和记忆的突触可塑性机制异常。然而，这些小鼠很少出现神经束缠结，也很少表现出突触和神经元的损失，这是阿尔茨海默病的特征。此外，这些家族性阿尔茨海默病模型可能对散发性（非家族性）阿尔茨海默病的研究意义不大，散发性阿尔茨海默病占阿尔茨海默病病例的95%左右。我们将研究使用啮齿动物章鱼作为模型研究散发性阿尔茨海默病的可行性。章鱼是一种昼行性、视觉性和高度社会性的啮齿动物，随着年龄的增长，自然会出现ad样病变，包括淀粉样斑块和神经丛缠结的积累。章鱼在区分新奇事物和熟悉事物的能力上也表现出明显的与年龄相关的衰退，这是一项有效的视觉记忆任务。我们推测，这种ad样病理的发展改变了神经突触的可塑性，损害了视觉记忆。为了验证这一假设，我们建议在个体中确定认知障碍的程度是否与突触可塑性和Ab沉积的缺陷相关。这些研究可以建立散发性阿尔茨海默病的动物模型，补充现有的家族性阿尔茨海默病模型。

DESCRIPTION (provided by applicant): Alzheimer disease (AD) is the most common neurodegenerative disease, characterized by progressive memory loss and massive cell death in the cerebral cortex. A predominant view of the cause of AD is that the amyloid accumulation is the essential event leading to neurodegeneration. This hypothesis is supported by research on transgenic mice expressing familial mutations of the human amyloid precursor protein (APP) and presenilins. These animals reproduce key aspects of the disease, including amyloid plaques, deficits in cognitive tasks and abnormalities in the mechanisms of synaptic plasticity responsible for learning and memory. However, these mice rarely develop neurobibrillary tangles and exhibit little synaptic and neuronal loss, hallmarks of AD. In addition, these models of familial forms of AD might be less significant to study sporadic (non-familial) forms of AD, which represent about 95% of AD cases. We will examine the feasibility of using the rodent Octodon degus as a model to study sporadic forms of AD. Octodon degus, is a diurnal, visual and highly social rodent that naturally develop AD-like pathologies including amyloid plaques and neurobrillary tangles accumulation with age. Octodon degus also exhibit a marked age-related decline in the ability to discriminate novel from familiar objects, a working visual memory task. We hypothesize that the development of AD-like pathologies in O.degus alters synaptic plasticity and impairs visual memory. To test this hypothesis, we propose to determine in individual O. degus whether the degree of cognitive impairments correlates with deficits in synaptic plasticity and the Ab deposits. These investigations could establish an animal model for sporadic AD that will complement existing models of familial forms of the disease.