Senile Degeneration in the Brain of Octogon Degus

描述(申请人提供)：阿尔茨海默病(AD)是最常见的神经退行性疾病，其特征是进行性记忆丧失和大脑皮层大量细胞死亡。对阿尔茨海默病病因的一个主要观点是，淀粉样蛋白堆积是导致神经退行性变的重要事件。对表达人类淀粉样前体蛋白(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的异常。然而，这些小鼠很少出现神经生物膜缠结，并且几乎没有突触和神经元丢失，这是AD的特征。此外，这些家族性AD模型对于研究散发性(非家族性)AD可能意义不大，因为散发性(非家族性)AD约占AD病例的95%。我们将研究以啮齿类动物Ocdon decus作为模型研究散发性AD的可行性。Ocdon decus，是一种昼夜活动、视觉和高度社会性的啮齿动物，随年龄增长自然发展为AD样病理，包括淀粉样斑块和神经纤维缠结堆积。奥特登·德格斯还表现出与年龄相关的明显下降，即区分小说和熟悉物体的能力，这是一项工作视觉记忆任务。我们推测，类AD病理的发展改变了突触的可塑性，损害了视觉记忆。为了验证这一假说，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抗体沉积的缺陷有关。这些研究可以为散发性阿尔茨海默病建立动物模型，补充现有的家族性疾病模型。

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.