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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 王培育(Pei-Yu Wang) | |
| dc.contributor.author | I-Ya Lin | en |
| dc.contributor.author | 林儀雅 | zh_TW |
| dc.date.accessioned | 2021-06-17T09:06:33Z | - |
| dc.date.available | 2025-03-13 | |
| dc.date.copyright | 2020-03-13 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-12-31 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74725 | - |
| dc.description.abstract | 飲食節制 (Dietary restriction) 在老化過程中扮演重要角色，許多實驗結果都證明了小鼠能夠透過飲食節制達到增強記憶以及延長壽命的效果。我們的實驗指出，補充人體所需必須胺基酸之一的色胺酸 (tryptophan) 會藉由通過血清素第六型受體 (serotonin receptor 6, HTR6) 進而消除飲食節制造成的記憶增強效果，以上
數據顯示 HTR6 的缺乏會誘導神經狀態改變並與飲食節制的結果相似。 本研究欲探討 HTR6 在老化過程中的作用，將以小鼠作為模式生物進行一系列的行為與代謝分析。我們發現在年輕小鼠上剔除 HTR6 基因並不影響體重、飲食和飲水量，而在肥胖小鼠和老年小鼠則會使體重下降。另外，與飲食節制小鼠相同的結果是，三組 HTR6 基因剔除小鼠均有記憶增強的效果，但並不影響運動、嗅覺以及其他認知功能。其他研究也發現 HTR6 基因剔除小鼠出現代謝上的改變；然而，海馬迴中被 HTR6 所調控之控管營養代謝的訊號分子－mammalian target of rapamycin complex 1 (mTORC1) 在周圍組織中並沒有受到 HTR6 基因剔除的影響。 為了進一步研究 HTR6 對壽命的潛在影響，我們使用生命週期較短的果蠅作為模式生物，並使用 GeneSwitch-Gal4 系統研究過度表達 HTR6 對於壽命的影響。實驗結果顯示過度表達 HTR6 會造成 TOR 訊號的增強，進而誘導果蠅壽命縮短。我們同時也觀察過度表達 HTR6 的果蠅的生理狀態，發現運動活性和耐飢餓能力皆顯著降低。此外，過度表達 HTR6 不會影響其他生理狀態，如食物的攝取、體重和繁殖力。 綜上所述，我們的結果證實剔除 HTR6 可延緩小鼠老化。相反的，過度表達HTR6 則會加速果蠅的老化。 | zh_TW |
| dc.description.abstract | Dietary restriction (DR) plays an important role in aging process and has been shown to induce memory enhancement and extend lifespan in mice. Our previous results showed that a single amino acid tryptophan, supplementation reverses the DR effects of memory enhancement through 5-hydroxytyptamine receptor 6 (HTR6). These findings suggested that HTR6 deficiency might induce a neurological state that mimics DR.
In this study, we aim to investigate the role of HTR6 during the aging process. Several experimental approaches including behavioral tests and metabolic profiles of wild-type and HTR6 knockout mice were examined. There was no difference in body weight, food and water intake in young mice, whereas reduced body weight was observed in the obese HTR6 KO mice and aged HTR6 KO mice without the alteration of food and water intake. Similar to the DR mice, HTR6 KO mice showed enhanced memory performance independent of age and diet, but we did not observe significant difference in motor, olfactory and other connective functions. In addition, we found altered metabolism in HTR6 KO mice, but HTR6 did not affect mTORC1 signaling in peripheral tissues. To further investigate the potential impact of HTR6 on lifespan, we used Drosophila to investigate the effect of HTR6 overexpression using GeneSwitch-Gal4 system (GS system). We observed shortened lifespan upon HTR6 overexpression in flies which were induced by TOR pathway. We observed reduced locomotor activity and reduced resistance to starvation in HTR6 overexpression flies. We observed no difference in food intake, body weight and fecundity between the control and HTR6 overexpression flies. In conclusion, our results suggest that loss of HTR6 prevents aging in mice. In contrast, overexpression of HTR6 accelerated aging by TOR pathway in flies. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T09:06:33Z (GMT). No. of bitstreams: 1 ntu-108-R06454003-1.pdf: 4752803 bytes, checksum: d1211e608147fdb2b8112eaacb91bf7d (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 口試委員會審定書 #
誌謝 i 中文摘要 ii Abstract iii Abbreviations iv Contents v Chapter 1 Introduction 1 1.1 The benefits of dietary restriction and the underlying mechanisms 1 1.2 Obesity accelerates the aging process 2 1.3 5-hydroxytyptamine receptor 6 (HTR6) 3 1.4 The relation between HTR6 and aging 4 Chapter 2 Materials and Methods 5 2.1 Animals 5 2.2 Behavioral tests 5 2.2.1 Open Field Test 5 2.2.2 Novel Object Recognition Test 6 2.2.3 Three-Chamber Social Test 6 2.2.4 Buried food test 7 2.2.5 Rotarod test 7 2.2.6 Tail suspension test 8 2.2.7 Forced swim test 8 2.3 Metabolic measurement 8 2.4 Glucose and insulin tolerance test 9 2.5 Fly stock 9 2.6 RU486 (Mifepristone) induction 10 2.7 Lifespan assays 10 2.8 Physiological measurements 10 2.8.1 Body weight and feeding assays 10 2.8.2 Fecundity assays 10 2.8.3 Locomotor activity 11 2.8.4 Starvation assays 11 2.9 Immunoblotting 11 2.10 Antibodies 12 2.11 RNA extraction and quantitative real-time PCR 12 2.12 Statistical analysis 13 Chapter 3 Results 14 3.1 HTR6 KO reduced body weight without the alteration of food and water intake in obese mice and aged mice 14 3.2 HTR6 KO mice have better memory performance 14 3.3 HTR6 KO does not impair motor, olfactory and other cognitive functions 15 3.4 The alterations of metabolism in HTR6 KO mice 15 3.5 HTR6 KO does not alter the expression of mTOR downstream signaling in peripheral tissues 17 3.6 HTR6 overexpression induced shorten lifespan in Drosophila melanogaster 17 3.7 HTR6 overexpression reduced locomotor activity and significantly less resistant to starvation in flies 18 Chapter 4 Discussion 19 Chapter 5 Figures 22 Chapter 6 References 39 | |
| dc.language.iso | zh-TW | |
| dc.subject | 代謝 | zh_TW |
| dc.subject | 老化 | zh_TW |
| dc.subject | 記憶 | zh_TW |
| dc.subject | 血清素受體 | zh_TW |
| dc.subject | aging | en |
| dc.subject | memory | en |
| dc.subject | metabolism | en |
| dc.subject | serotonin receptor | en |
| dc.title | 血清素受體 HTR6 在老化過程中的角色 | zh_TW |
| dc.title | The role of serotonin receptor HTR6 in aging | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 范守仁(Shou-Zen Fan),汪宏達(Horng-Dar Wang) | |
| dc.subject.keyword | 老化,記憶,代謝,血清素受體, | zh_TW |
| dc.subject.keyword | aging,memory,metabolism,serotonin receptor, | en |
| dc.relation.page | 44 | |
| dc.identifier.doi | 10.6342/NTU201902650 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-01-02 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 腦與心智科學研究所 | zh_TW |
| Appears in Collections: | 腦與心智科學研究所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-108-1.pdf Restricted Access | 4.64 MB | Adobe PDF |
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