Senile Degeneration in the Brain of Octogon Degus

阿尔茨海默病（Alzheimer disease，AD）是最常见的神经退行性疾病，其特征在于进行性痴呆， 记忆丧失和大脑皮层大量细胞死亡关于AD的原因的一个主要观点是， 淀粉样蛋白积累是导致神经变性的基本事件。这一假设得到了支持 通过对表达人类淀粉样前体蛋白（APP）家族突变的转基因小鼠的研究， 和早老素。这些动物复制疾病的关键方面，包括淀粉样蛋白斑块， 认知任务和负责学习的突触可塑性机制异常， 记忆然而，这些小鼠很少发生神经bibrillary缠结，并且几乎没有突触和神经元 损失，AD的标志。此外，这些家族性AD模型的研究意义可能较小， AD的散发（非家族性）形式，其代表约95%的AD病例。我们会研究 使用啮齿类动物作为模型来研究AD的散发形式。德古斯，是一个昼夜， 视觉和高度社会化的啮齿类动物，其自然发展为AD样病理，包括淀粉样斑块， 神经纤维缠结随着年龄的增长而积累。Dedon degus也表现出明显的年龄相关性下降， 区分新奇事物和熟悉事物的能力，这是一项工作视觉记忆任务。我们假设 在O.degus中AD样病理的发展改变了突触可塑性并损害视觉记忆。测试 这个假设，我们建议确定在个人O。degus是否认知障碍的程度 与突触可塑性和Ab沉积的缺陷相关。这些调查可以建立一个 散发性AD的动物模型，将补充现有的家族性AD模型。

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.