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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 張芳嘉(Fang-Chia Chang) | |
dc.contributor.author | Yu-Jie Liu | en |
dc.contributor.author | 劉妤婕 | zh_TW |
dc.date.accessioned | 2021-06-17T04:24:31Z | - |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-08-20 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70228 | - |
dc.description.abstract | 人口高齡化現在已經成為全球普遍的現象,阿茲海默症 (Alzheimer’s disease, AD) 的發病率伴隨著年齡的增長而急劇增加。阿茲海默症是一種漸進性神經退化疾病,會損害記憶力和認知障礙,目前缺乏對阿茲海默症病因的完全了解,所以透過動物的主動操作或使用轉基因動物模型來模擬疾病,進行相關研究。此外,研究已指出阿茲海默症病理特徵澱粉斑塊 (Amyloid-beta, Aβ) 和神經原纖維纏結 (Neurofibrillary tangles, NFT),會促使發炎因子的釋放,例如發炎因子第一介白素 (Interleukin-1, IL-1β),其為睡眠調節物質,睡眠也在Aβ的清除中也扮演了關鍵的角色,並影響阿茲海默症的病情。NMDA受體(N-methyl-D-aspartate receptor, NMDAR) 為谷氨酸受體,對於神經元的突觸可塑性和存活至關重要,被認為是學習和記憶的基礎,在臨床上與阿茲海默症患者中認知、記憶的逐步下降以及病理性神經解剖結構的發展相關。因此,本研究藉由注射不溶性的澱粉蛋白來誘導阿茲海默症,並探討第一介白素和NMDAR與阿茲海默症誘發之睡眠障礙之關係。 本研究使用腦室注射不溶性Aβ1-42以誘發阿茲海默症,並分析辨識以及空間記憶之行為。在免疫螢光染色上可以看到Aβ的累積,且注射Aβ1-42的組別運動能力都不佳,給予低劑量Aβ的組別辨識記憶也明顯受損;而空間記憶能力則沒有看出比較明顯的差異,此結果顯示腦室注射Aβ1-42確實會造成Aβ的累積以及辨識記憶能力下降。另一方面,經由Aβ注射後,NR2B亞單位在前額葉皮質則有顯著減少,初步結果表示阿茲海默症病理學會導致NMDAR下調。 總結以上,此研究結果顯示,利用腦室注射Aβ能誘發阿茲海默症的辨識記憶障礙,並且會影響NMDAR之活化。 | zh_TW |
dc.description.abstract | Population aging has become a worldwide phenomenon. Alzheimer’s disease (AD) frequency increases strongly with age. AD is a progressive neurodegenerative disease that causes memory loss and cognitive impairment. Because the lack of full understanding of AD, simulating the disease with active operation of animals or using genetically modified animal models is commonly used to understand the pathophysiology. Evidence has demonstrated that the pathological markers of Alzheimer's disease, amyloid-beta (Aβ) deposition and neurofibrillary tangles (NFT), promote the release of pro-inflammatory cytokines, such as IL-1β. IL-1 is a sleep-regulating substance, and sleep plays a key role in the removal of Aβ and affects the progression of AD. NMDA receptor (N-methyl-D-aspartate receptor, NMDAR) is a high-density glutamate receptor and is essential for neurotransmission, neuronal synaptic plasticity and neuronal survival. NMDAR is considered to be the foundation of learning and memory which correlates clinically with the progressive decline in cognition/memory and the development of pathological neural anatomy seen in AD patients. Therefore, we studied induced-AD by injecting insoluble Aβ, and explored the relationship between interleukin-1 and NMDAR in Alzheimer's disease and AD-induced sleep disruption. In this study, the AD animal model was induced by Intracerebroventricular injection of insoluble amyloid Aβ1-42, the behaviors of identification and spatial memory were analyzed. We found that the poor locomotion activity was significant observed in the mice treated with Aβ1-42 than that treated with vehicle (NH4OH). Furthermore, the recognition memory was impairment in mice treated with Aβ1-42, but spatial memory was not altered. This result indicated the AD model caused a decline in the ability to recognize novel object and spatial memory. The expression of NR2 subunit protein of NMDAR in the prefrontal cortex was significantly lower in the mice treated with Aβ1-42. These findings suggest that amyloid-beta contributes to the down-regulation of NMDAR. In conclusion, our results indicated that the decrease of NMDAR activity by amyloid-beta may be the cause to impair memory. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T04:24:31Z (GMT). No. of bitstreams: 1 U0001-1708202015033000.pdf: 4048526 bytes, checksum: d09e77130f4103518a079157814a1de0 (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 口試委員會審定書 ii 誌謝 iii 中文摘要 iv 英文摘要 v 目錄 vi 圖目錄 x 表目錄 xii 第一章、前言 1 1.1 阿茲海默症(Alzheimer's disease, AD) 1 1.1.1 流行病學 1 1.1.2 發病原因 1 1.1.3 病理機制 2 1.2 第一介白素(Interleukin-1, IL-1) 4 1.2.1 簡介 4 1.2.2 IL-1受體在阿茲海默症之作用 5 1.2.3 IL-1參與睡眠的調節 6 1.3 N-甲基-D-天門冬氨酸受體 (N-methyl-D-aspartate receptor, NMDAR) 7 1.3.1 簡介 7 1.3.2 NMDA受體與阿茲海默症 8 1.4 清除機制 8 1.4.1 睡眠和Aβ的關係 8 1.4.2 β澱粉蛋白的清除機制 10 1.5 研究目的 11 第二章、材料與方法 12 2.1 實驗動物 12 2.1.1 簡介 12 2.1.2 飼養條件 12 2.2 實驗方法-藥物測試 12 2.2.1 手術 12 2.2.2 實驗流程 13 2.3 實驗方法-行為測試 14 2.3.1 曠野實驗 (Open field test, OFT) 14 2.3.2 新奇事物認知測試( Novel object recognition test, NOR ) 15 2.3.3 空間事物認知測試 ( Spatial object recognition test, SOR ) 16 2.3.4 巴恩斯迷宮 (Barnes maze) 16 2.3.5 莫里斯水迷宮(Morris water maze, MWM) 17 2.4實驗方法-睡眠測試 18 2.4.1 手術 18 2.4.2 實驗流程 19 2.5實驗方法-蛋白表現測試 20 2.5.1 實驗流程 20 2.5.2 蛋白質濃度分析 21 2.5.3 SDS-聚丙烯醯胺膠體電泳 22 2.6實驗方法-免疫螢光染色 24 2.6.1 實驗流程 24 2.6.2 腦組織切片 24 2.6.3 免疫螢光染色 25 2.7 EEG紀錄分析 25 2.7.1 紀錄 25 2.7.2 分析 25 2.8數據統計 26 第三章、結果 27 3.1低劑量藥物注射對老鼠造成之影響 27 3.1.1 給予低劑量Aβ後腦內斑塊累積之情形 27 3.1.2 給予低劑量Aβ後老鼠活動力狀況 27 3.1.3 給予低劑量Aβ後老鼠物體辨識的能力 28 3.1.4 給予低劑量Aβ後老鼠空間中物體位移辨識的能力 29 3.1.5 給予低劑量Aβ後老鼠空間記憶的能力 29 3.2給予低劑量/高劑量藥物注射對老鼠造成之影響 31 3.2.1 給予低劑量/高劑量Aβ後老鼠游泳活動力的狀況 31 3.2.2 給予低劑量/高劑量Aβ後老鼠空間記憶的能力 32 3.3給予高劑量藥物注射對老鼠造成之影響 34 3.3.1 給予低劑量/高劑量Aβ後腦內斑塊累積之情形 34 3.3.2 給予高劑量Aβ後老鼠的活動力狀況 34 3.3.3 給予高劑量Aβ後老鼠物體辨識的能力 35 3.3.4 給予高劑量Aβ後老鼠空間中物體位移辨識的能力 36 3.3.5 給予高劑量Aβ後老鼠空間記憶的能力 37 3.4阿茲海默症動物模型蛋白表現量 39 3.4.1 給予高劑量Aβ後NR1的蛋白表現量 39 3.4.2 給予高劑量Aβ後NR2的蛋白表現量 40 3.4.3 給予低劑量Aβ後NR2的蛋白表現量 41 3.5阿茲海默症動物模型睡眠之變化 42 3.5.1 給予高劑量Aβ後NREM睡眠變化 42 第四章、討論 44 4.1分析ICV注射Aβ誘導之動物模型 44 4.1.1 Scramble Aβ對於老鼠的影響 44 4.1.2 高劑量Aβ對於老鼠的影響 45 4.1.3 注射Aβ對於老鼠空間記憶的影響 45 4.1.4 注射Aβ對於NMDAR的影響 46 4.1.5 注射Aβ對於老鼠睡眠的影響 46 第五章、結論 47 第六章、參考資料 48 第七章、附錄 55 | |
dc.language.iso | zh-TW | |
dc.title | 探討第一介白素與NMDA受體於Aβ誘發阿茲海默氏症動物模型中所扮演的角色 | zh_TW |
dc.title | The Role of IL-1β and NMDA Receptor in Aβ-induced Animal Model of Alzheimer’s Disease | en |
dc.type | Thesis | |
dc.date.schoolyear | 109-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 周碩彬(Shuo-Bin Jou),尹珮璐(Pei-Lu Yi),蕭逸澤(Yi-Tse Hsiao) | |
dc.subject.keyword | 阿茲海默症,澱粉蛋白,第一介白素,NMDA受體,睡眠障礙, | zh_TW |
dc.subject.keyword | Alzheimer's disease,Aβ,IL-1,NMDA receptors,Sleep disorders, | en |
dc.relation.page | 59 | |
dc.identifier.doi | 10.6342/NTU202003760 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-08-20 | |
dc.contributor.author-college | 獸醫專業學院 | zh_TW |
dc.contributor.author-dept | 獸醫學研究所 | zh_TW |
顯示於系所單位: | 獸醫學系 |
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