本文選題：阿爾茲海默病　切入點(diǎn)：APP/PS1轉(zhuǎn)基因小鼠　出處：《中國科學(xué)院研究生院（武漢物理與數(shù)學(xué)研究所）》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：阿爾茲海默病(Alzheimer's disease, AD)是老年癡呆病中較常見的一種,其最為顯著的病理特征是神經(jīng)元纖維纏結(jié)和老年斑的沉積,典型的早期臨床癥狀是記憶衰退。AD患者的病情一般隨年齡的增長而加劇,最終出現(xiàn)記憶喪失、思維等認(rèn)知功能障礙等癥狀。磁共振成像(magnetic resonance imaging, MRI)等影像手段檢測發(fā)現(xiàn)AD患者海馬萎縮,且與其認(rèn)知功能障礙有顯著的相關(guān)性。AD的病程緩慢且不可逆,目前尚不可治愈。AD患者生活無法自理,需要有專人照顧,給家庭和日漸老齡化的社會帶來巨大壓力。AD的致病機(jī)制以及有效的治療方法已經(jīng)成為醫(yī)學(xué)界不可忽視的研究熱點(diǎn)。 豐富環(huán)境(enriched environment, EE)是指在生存環(huán)境和社會交往兩個方面相對于標(biāo)準(zhǔn)環(huán)境更加復(fù)雜的環(huán)境,具體表現(xiàn)為多感官刺激、自愿物理運(yùn)動、社會性刺激及相互交往機(jī)會的增多。大量前人的實(shí)驗(yàn)室研究發(fā)現(xiàn),豐富環(huán)境干預(yù)可以做為一種簡便、有效的手段,增加智力,延緩衰老,減緩神經(jīng)退行性病變的進(jìn)程,促進(jìn)受損后大腦的恢復(fù)。豐富環(huán)境刺激也已被證明能促進(jìn)海馬神經(jīng)元的發(fā)生和突觸的可塑性,增加海馬新生神經(jīng)元數(shù)量,緩解AD轉(zhuǎn)基因動物的認(rèn)知損傷。 本論文工作旨在研究長期豐富環(huán)境飼養(yǎng)對野生型和APPswe/PS1dE9轉(zhuǎn)基因小鼠大腦結(jié)構(gòu)的影響。實(shí)驗(yàn)采集了不同年齡段野生型及轉(zhuǎn)基因小鼠腦部的高分辨結(jié)構(gòu)像和擴(kuò)散加權(quán)像,并采用基于形變的形態(tài)測量學(xué)(DBM)、基于體素的形態(tài)測量學(xué)(VBM)對結(jié)構(gòu)像數(shù)據(jù)進(jìn)行處理,采用基于體素的分析方法(VBA)、基于纖維束的空間統(tǒng)計方法(TBSS)對擴(kuò)散加權(quán)數(shù)據(jù)進(jìn)行處理,探究長期豐富環(huán)境對野生型及APPswe/PS1dE9轉(zhuǎn)基因小鼠全腦體積、灰質(zhì)(grey matter, GM)體積、白質(zhì)(white matter, WM)體積、白質(zhì)纖維束微結(jié)構(gòu)(microstructure)的影響。 實(shí)驗(yàn)發(fā)現(xiàn)長期的豐富環(huán)境飼養(yǎng)能夠增大APPswe/PS1dE9小鼠(≥6月齡)海馬CA1和CA3區(qū)的體積,增加其外囊白質(zhì)纖維束的各向異性分?jǐn)?shù)(fractional anisotropy, FA)值。我們的結(jié)果提示,豐富環(huán)境能夠改善APPswe/PS1dE9轉(zhuǎn)基因小鼠的海馬及外囊的受損情況,并能在一定程度上修復(fù)其額葉-顳葉、額葉-頂葉的功能聯(lián)絡(luò),進(jìn)而解釋豐富環(huán)境刺激為什么能夠緩解AD轉(zhuǎn)基因動物的認(rèn)知損傷。
[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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