长期丰富环境对阿尔兹海默病转基因小鼠大脑结构的影响

发布时间：2018-03-23 01:09

  本文选题：阿尔兹海默病　切入点：APP/PS1转基因小鼠　出处：《中国科学院研究生院（武汉物理与数学研究所）》2013年硕士论文　论文类型：学位论文

【摘要】：阿尔兹海默病(Alzheimer's disease, AD)是老年痴呆病中较常见的一种,其最为显著的病理特征是神经元纤维缠结和老年斑的沉积,典型的早期临床症状是记忆衰退。AD患者的病情一般随年龄的增长而加剧,最终出现记忆丧失、思维等认知功能障碍等症状。磁共振成像(magnetic resonance imaging, MRI)等影像手段检测发现AD患者海马萎缩,且与其认知功能障碍有显著的相关性。AD的病程缓慢且不可逆,目前尚不可治愈。AD患者生活无法自理,需要有专人照顾,给家庭和日渐老龄化的社会带来巨大压力。AD的致病机制以及有效的治疗方法已经成为医学界不可忽视的研究热点。 丰富环境(enriched environment, EE)是指在生存环境和社会交往两个方面相对于标准环境更加复杂的环境,具体表现为多感官刺激、自愿物理运动、社会性刺激及相互交往机会的增多。大量前人的实验室研究发现,丰富环境干预可以做为一种简便、有效的手段,增加智力,延缓衰老,减缓神经退行性病变的进程,促进受损后大脑的恢复。丰富环境刺激也已被证明能促进海马神经元的发生和突触的可塑性,增加海马新生神经元数量,缓解AD转基因动物的认知损伤。 本论文工作旨在研究长期丰富环境饲养对野生型和APPswe/PS1dE9转基因小鼠大脑结构的影响。实验采集了不同年龄段野生型及转基因小鼠脑部的高分辨结构像和扩散加权像,并采用基于形变的形态测量学(DBM)、基于体素的形态测量学(VBM)对结构像数据进行处理,采用基于体素的分析方法(VBA)、基于纤维束的空间统计方法(TBSS)对扩散加权数据进行处理,探究长期丰富环境对野生型及APPswe/PS1dE9转基因小鼠全脑体积、灰质(grey matter, GM)体积、白质(white matter, WM)体积、白质纤维束微结构(microstructure)的影响。 实验发现长期的丰富环境饲养能够增大APPswe/PS1dE9小鼠(≥6月龄)海马CA1和CA3区的体积,增加其外囊白质纤维束的各向异性分数(fractional anisotropy, FA)值。我们的结果提示,丰富环境能够改善APPswe/PS1dE9转基因小鼠的海马及外囊的受损情况,并能在一定程度上修复其额叶-颞叶、额叶-顶叶的功能联络,进而解释丰富环境刺激为什么能够缓解AD转基因动物的认知损伤。
[Abstract]:Alzheimer's disease (ADD) is one of the most common diseases in Alzheimer's disease. The most prominent pathological features are neuronal fibrillary tangles and the deposition of senile plaques. A typical early clinical symptom is memory decline. The condition of patients with AD generally increases with age, leading to memory loss. Magnetic resonance imaging (MRI) and other imaging methods showed that the hippocampus atrophy in AD patients was significantly correlated with cognitive dysfunction. The course of AD was slow and irreversible. At present, the patients who can not be cured can not take care of themselves, need special care, bring great pressure to the family and aging society, the pathogenic mechanism of AD and effective treatment methods have become a research hotspot that can not be ignored in the field of medicine. Rich environment (EEE) refers to a more complex environment than the standard environment in terms of living environment and social interaction, which is manifested in multi-sensory stimulation and voluntary physical movement. Increasing opportunities for social stimulation and interaction. A large number of previous laboratory studies have found that rich environmental intervention can be used as a simple and effective means to increase intelligence, delay aging and slow down the progress of neurodegenerative diseases. Rich environmental stimuli have also been shown to promote the development of hippocampal neurons and synaptic plasticity, increase the number of hippocampal neonate neurons and alleviate cognitive impairment in AD transgenic animals. The purpose of this paper is to study the effects of long-term enriched environment on the brain structure of wild type and APPswe/PS1dE9 transgenic mice. The high-resolution and diffusion-weighted images of brain of wild type and transgenic mice of different ages were collected. The structural image data were processed by deformation-based morphometry (DBM), voxel based morphometry (VBM), voxel based analysis (VBAA) and fiber bundle based spatial statistics (TBSS) to process diffusion-weighted data. To explore the effects of long-term rich environment on the whole brain volume, grey grey matter volume, white matter white matter volume and microstructureof white matter bundles in wild-type and APPswe/PS1dE9 transgenic mice. It was found that long-term enrichment could increase the volume of CA1 and CA3 in hippocampus of APPswe/PS1dE9 mice (鈮，

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