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標題: | 三重轉基因阿茲海默氏症小鼠的體重、行為、代謝及病理變化 Weight, behavior, metabolism and amyloid pathology in triple transgenic Alzheimer’s mice |
作者: | Boon-Lead Tee 鄭文立 |
指導教授: | 邱銘章(Ming-Jang, Chiu) |
關鍵字: | 阿?海默症,代謝,體重,杏仁核, Alzheimer’s disease,Metabolism,Body weight,Amygdala, |
出版年 : | 2017 |
學位: | 碩士 |
摘要: | 背景:阿兹海默病是一種神經退行性疾病並以認知功能退化著稱。然而越來越多證據顯示阿兹海默症也會表現非認知功能的症狀,例如體重改變,睡眠和精神症狀。此外,研究者發現這些非認知功能的症狀會出現於阿茲海默症的早期,甚至會早於認知功能惡化前出現。以腦部各區塊的功能性考量,與這些非認知症狀相關的部位包含了下丘腦和杏仁體。從病理學而言,典型的阿兹海默症病理學表現主要以神經原纖維纏結和澱粉樣斑塊組成。這意味著阿兹海默症的病理生理學中tau蛋白和類澱粉蛋白扮演了重要的角色。三轉基因阿茲海默症老鼠具有tau蛋白和類澱粉蛋白的基因變化,是病理上與人類阿茲海默症最相似的老鼠模型。因此透過觀察三轉基因阿茲海默症老鼠,我們希望可以更了解阿茲海默症的非認知症狀,並探討這些非認知症狀與神經病理學之間的關聯。
研究方法:首先我們監測三轉基因阿茲海默症老鼠從4週齡至40週齡的體重、食物和水攝入量。透過間接測熱量儀,獲取代謝速率和活動量的數據。最後分批犧牲小鼠以完成澱粉樣蛋白病理學的免疫組織化學。 結果:三轉基因阿茲海默症雌性小鼠於4週齡時體重較輕,然而牠們體重增加的速度較快,於40週齡時反而超過對照小鼠,比對照小鼠的體重更重。三轉基因阿茲海默症雌性小鼠表現出更高的食物攝入量及較低的活動量,這可間接解釋為何三轉基因阿茲海默症雌性小鼠的體重上升較快。除此之外,病理染色分析發現體重和攝食量與三轉基因阿茲海默症雌性小鼠的杏仁核中的凋亡神經元數呈高度正相關(ρ分別0.86,0.88)。 結論:這項研究演示了三轉基因阿茲海默症雌性小鼠中的體重增加的過程,這可能歸因於相對性的食慾過盛和較低的身體活動量。此一體重增長和攝食量上升的行為可能與杏仁核病理學的變化相關。 Background: Alzheimer’s disease (AD) is a neurodegenerative disease well recognized for its cognitive decline features. Yet increasing evidence has indicated that AD also developed noncognitive symptoms such as body weight alterations, sleep and psychiatric symptoms. Furthermore, researches suggest that these noncognitive symptoms occurs early in the clinical course of AD and may even precede the cognitive deterioration of AD. Candidate brain regions responsible for these noncognitive symptoms includes hypothalamus and amygdala. Typical AD pathology mainly composed of neurofibrillary tangles and amyloid plaques which implied a combined role of taupathy and amyloidogenesis in the pathophysiology of AD. Using triple transgenic mice of Alzheimer’s disease that possess both taupathy and amyloidogenesis characteristic, we aim to decipher the noncognitive symptoms in early AD and attempt to correlate these noncognitive symptoms with neuropathological findings. Methods: Body weight, food and water intake were repeatedly measured in triple transgenic mice of Alzheimer’s disease (3xTg AD mice) and non-transgenic control mice from 4 to 4o week-old. Metabolic rate and physical activity data was obtained via indirect calorimetry. Mice were then sacrificed for immunohistochemistry stain on amyloid pathology. Results: 3xTg AD female mice weighs lighter at 4 week-old but gain weight at a faster pace and weigh heavier than non-Tg control mice at 40 week-old. A higher intake amount and lower physical activity was noted in 3xTg AD female mice. Body weight and amount of food intake were found to be well correlated with number of pyknotic cells in amygdala (ρ= 0.86, 0.88 respectively). Lower physical activity was moderately correlated with number of amyloid cells in secondary motor cortex (ρ=0.64). Conclusion: This study demonstrated a gradual weight gain process in 3xTg AD female mice and is possibly attributed to relative hyperphagia and lower physical activity. This body weight alteration and hyperphagia behavior may be associated with amygdala pathology. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59748 |
DOI: | 10.6342/NTU201700442 |
全文授權: | 有償授權 |
顯示於系所單位: | 臨床醫學研究所 |
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