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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王培育 | |
| dc.contributor.author | Ya-Yun Cheng | en |
| dc.contributor.author | 鄭雅云 | zh_TW |
| dc.date.accessioned | 2021-06-08T02:27:06Z | - |
| dc.date.copyright | 2015-09-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19919 | - |
| dc.description.abstract | 卡路里節制(Calorie Restriction, CR)在許多不同物種上已被發現能有效降低與老化相關疾病發生的風險，以及增進認知功能的效果。然而，飲食成分中，哪一種營養成分扮演了主要的角色，藉由卡路里的節制調控了認知功能的可塑性。在本篇論文中，在不同營養成分下，本實驗利用物體辨認測驗(Novel Object Recognition, NOR)評估小鼠的記憶功能以及利用廣場測驗(Open Field Test)檢視小鼠自發性活動能力。發現飲食成分中的蛋白質(Protein)，其中的必需胺基酸-色胺酸(Tryptophan) 在卡路里節制的情況下扮演了主要的角色促使記憶的增強。本研究結果更進一步顯示: 卡路里節制能調控認知記憶功能，且需要藉由海馬迴(Hippocampus)裡的腺苷單磷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)活化的參與。另外，實驗結果發現AMPK的促進劑，Metformin，可以有效地增強小鼠的記憶表現；然而，AMPK的抑制劑，Compound C(CC)，能有效地反轉因卡路里節制而增強記憶的好處。綜合以上所有結果顯示: 本篇論文鑑定出小鼠在卡路里節制的情況下，飲食成分中的色胺酸，為最主要能調控並促進記憶增強的營養成分，且其過程必須透過海馬迴內AMPK的活化。該研究結果強烈顯示，其結果在臨床治療與老化相關的腦功能障礙上具有重要意義。 | zh_TW |
| dc.description.abstract | Calorie restriction (CR) has been shown to reduce the incidence of age-related diseases and improve cognitive functions in a variety of species. However, it remains unknown as to whether specific nutrient primarily works to mediate CR-induced cognitive plasticity. In this study, I evaluated the memory functions of mice under different dietary conditions by novel object recognition (NOR) tasks and the spontaneous motor activity by open field test. I found that protein derived essential amino acid-tryptophan played a major role in CR-induced memory enhancement. My results further revealed that hippocampal AMPK activation is essential for CR-mediated cognitive memory regulation since AMPK activation. I found that metformin, an AMPK activator, could significantly enhance the memory performance of mice, while CR-induced memory enhancement was attenuated by Compound C (CC), an AMPK inhibitor. Taken together, this study identified tryptophan as a critical nutrient that could mediate improved recognition memory essentially through AMPK activation under CR condition in mice. This study may have a critical implication in treating age-related brain dysfunctions in a clinical setting. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T02:27:06Z (GMT). No. of bitstreams: 1 ntu-104-R02454013-1.pdf: 3028140 bytes, checksum: 4a6e521ab3d1847bf08a2063b42a3e17 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | Acknowledgement……………………………………………………………………i 中文摘要………………………………………………………………………………ii Abstract……………………………………………………………..……………...…iii Chapter 1 Introduction…………………………………..…...………………1 1-1 Caloric restriction……………………………………………...……..……………1 1-2 Nutrient restriction…………………………………………...……..……………..2 1-3 Metabolisms…………………………………………...……..……………………3 Chapter 2 Materials and Methods…………...……...……..………………5 2-1. Animals………………...……..……………………………..……..……………5 2-2. Diets………………...……..……………………………..…..……..……………5 2-2-1. Caloric restriction diet……………………………..…..……..………...…5 2-2-2. nutritional manipulation……………………………..…..……..…………6 2-2-3. metformin diet…………………………...…………..…..……..…………6 2-3. Drug treatments………………..……………...…………..…..……..…………6 2-4. Behavioral Tests………………..……………...……...…..…...……..…………6 2-4-1. Open Field Test………………..………...……….....…...……..…………7 2-4-2. Novel Object Recognition Test………...……….....…...…………………7 2-5. Western Blot………...……….....…...…………………………………………..9 2-6. Statistical analysis………...……….....…...………………...…………………10 Chapter 3 Results…...……….....…...………………………………...………11 3-1. CR improves recognition memory in mice……………………..………………11 3-2. The duration of CR effects on the memory performance of mice……………...14 3-3. Protein mediates CR-induced memory enhancement………………..…….…...15 3-4. Tryptophan mediates CR-induced memory enhancement…………..……..…...16 3-5. HTR6 KO mice do not respond to tryptophan supplementation……..……..….17 3-6. AMPK mediates CR-induced memory enhancement……..…………….…..….18 Chapter 4 Discussion……..………………………………….…...….…..…...20 List of Figures……..………………………………….………………….…..…...25 Fig.1 Chronic CR improves memory but not affects motor activity in mice. …..…...25 Fig. 2 Appetite may not affect the memory performance of mice. …..…...................27 Fig. 3 The duration of CR effects on the memory performance of mice. ...................29 Fig. 4 Protein mediates CR-induced memory enhancement. ......................................30 Fig. 5 Tryptophan mediates CR-induced memory enhancement. ...............................32 Fig. 6 HTR6 KO mice do not respond to tryptophan supplementation. .....................34 Fig. 7 Nutritional manipulation induces AMPK activation in mouse hippocampus. .36 Fig8. Hippocampal AMPK activation enhances memory performance in mice. .......37 Fig9. AMPK activation is required for CR-induced memory enhancement in mice. .39 Reference……..……………………………………………….….…….….....…....41 | |
| dc.language.iso | en | |
| dc.title | 飲食操弄對於小鼠記憶的影響 | zh_TW |
| dc.title | Effects of nutritional manipulations on memory in mice | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蔡亭芬,梁庚辰,廖瑞銘 | |
| dc.subject.keyword | 卡路里節制,再認記憶,蛋白質,色胺酸,AMPK,物體辨認測驗, | zh_TW |
| dc.subject.keyword | calorie restriction,protein,tryptophan,AMPK,memory,NOR, | en |
| dc.relation.page | 46 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2015-08-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 腦與心智科學研究所 | zh_TW |
| 顯示於系所單位： | 腦與心智科學研究所 | |
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