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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 歐展言 | zh_TW |
| dc.contributor.advisor | Chan-Yen Ou | en |
| dc.contributor.author | 王荷昱 | zh_TW |
| dc.contributor.author | Ho-Yu Wang | en |
| dc.date.accessioned | 2021-07-11T15:21:19Z | - |
| dc.date.available | 2024-08-16 | - |
| dc.date.copyright | 2019-03-11 | - |
| dc.date.issued | 2019 | - |
| dc.date.submitted | 2002-01-01 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78814 | - |
| dc.description.abstract | 神經(neuron)為生物體中用來接收、傳遞訊息的細胞，主要結構為細胞本體(cell body)、接收訊息的樹突(dendritie)以及送出訊息的軸突(axon)。粒線體(mitochondrion)為細胞最主要用來生成能量的胞器，當粒線體能量供給出問題，會造成神經發育異常或功能受損而導致神經退化性疾病，例如帕金森氏症。先前研究指出，PTEN-誘導激酶1(PINK1)和E3泛素連接酶(Parkin)調控粒線體自噬作用(mitophagy)來清除細胞中受損的粒線體，而PINK1或Parkin異常是導致帕金森氏症的主要原因之一。然而，目前仍然沒有一個適合的活體模式系統來研究PINK1、Parkin以及他們的下游因子對於粒線體的調控與神經樹突形態之間的關係。在我的研究中，我首先證明在線蟲PVD神經元中粒線體的分布以及分裂融合均會影響神經樹突的型態生長，且粒線體的存在可以穩定生長中的樹突不進行無謂的分支。進一步，我發現缺乏PINK1或Parkin均會造成樹突長度和分支的減少。另一方面，在粒線體的觀察中我發現，缺乏Parkin的情況下，許多軸突中的粒線體會變小且模糊化，細胞本體也會出現許多不正常的粒線體顆粒，而這些顆粒的產生需要發動相關蛋白1(Drp1)，同時也部分需要PINK1。然而，缺乏粒線體Rho GTP酶1 (Miro1)會更加促進這些不正常顆粒的產生。最後，我發現缺乏粒線體融合蛋白(mitofusin)會造成粒線體細碎化並且亮度與數量均會減少，而同時缺乏Parkin能夠稍微回復粒線體的亮度與數量，代表去除Parkin有助於細碎的粒線體聚集。總而言之，我在活體生物中一個特定的神經細胞檢驗粒線體與神經樹突的關係，並觀察到了缺乏PINK1、Parkin和其下游因子對於粒線體型態的影響，以及造成樹突在生長上的缺陷。 | zh_TW |
| dc.description.abstract | Neuron is a cell type that functions in receiving signals, integrating incoming signals and sending signals to target cells, and its compartments include cell body, dendritie and axon. Mitochondrion is an organelle which generates most of ATP, as source of chemical energy. Defect of generating energy in mitochondria may affects neuronal morphology and function, and causes neurodegerative diseases, such as Parkinson’s disease. Previous studies reported that PINK1 and Parkin regulate mitophagy to eliminate damaged mitochondria, deficiency of PINK1 or Parkin cause Parkinson’s disease. However, there is still no robust model to study how PINK1, Parkin and their substrates regulate mitochondria and affect dendritic morphology in vivo. In my study, I confirmed that both mitochondrial localization and dynamics affect dendritic morphogenesis in C. elegan PVD neuron, and mitochondrial can stabilize dendritic branching. Next, I found the decrease of dendritic length and branches in mutation of PINK1/pink-1 and Parkin/pdr-1. In my observation, I found numbers of small and blurred mitochondria in axon and abnormal mitochondrial puncta in cell body in pdr-1 mutant. The abnormal puncta in cell body require Drp1 and also partially require PINK1. Furthermore, loss of Miro1 enhances the generating of abnormal mitochondrial puncta. Finally, mutation of mitofusin/fzo-1 caused mitochondrial fragmentation and decrease of mitochondrial intensity and number, however, the defects were slightly rescued in pdr-1; fzo-1 mutant, indicating that loss of Parkin promotes fragmented mitochondria to aggregate. Taken together, I established a platform which allows us to examine the relationship between mitochondria and dendrite in a specific neuron in vivo, and found that impairment of PINK1, Parkin or their substrates affect mitochondrial and dendritic morphology. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:21:19Z (GMT). No. of bitstreams: 1 ntu-108-R03442026-1.pdf: 9736481 bytes, checksum: 240196e21e0eca9ef3b809e566079615 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 中文摘要............................................................................................................................i
ABSTRACT....................................................................................................................iii CONTENTS.....................................................................................................................v I. INTRODUCTION........................................................................................................1 1.1 The relationship between mitochondria and neuronal morphology........................1 1.2 The mechanism of mitochondrial dynamics and transport......................................2 1.3 Parkinson’s disease and the role of PINK1/Parkin pathway....................................4 1.4 The relationship between PINK1/Parkin pathway and mitochondrial dynamics or transport...................................................................................................................5 II. MATERIALS AND METHODS...............................................................................8 2.1 Strains and Genetics................................................................................................8 2.2 Designing an integrated line to observe mitochondria and neuronal morphology in PVD neuron.............................................................................................................8 2.3 Constructs and transgenic worms............................................................................8 2.4 Protocol of generating transgenic integrated line..................................................11 2.5 Combination of different genotypes......................................................................12 2.6 Worm lysis for genomic DNA...............................................................................13 2.7 Imaging and quantification....................................................................................13 2.8 Time lapse imaging................................................................................................14 2.9 Airyscan imaging...................................................................................................15 III. RESULTS.................................................................................................................16 3.1 Mitochondrial localization affects dendritic growth and branching......................16 3.2 Not only localization, mitochondrial dynamics also affect dendritic morphogenesis.......................................................................................................18 3.3 Mitochondria stabilize 2° dendritic growth...........................................................19 3.4 Examining parkinson’s disease related genes, pink-1 and pdr-1, in mitochondria and dendritic morphology......................................................................................20 3.5 Drp1 is required for the abnormal mitochondrial puncta in cell body of pdr-1....23 3.6 Loss of Miro1 enhances the occurrence rate of abmormal mitochondrial puncta in cell body.................................................................................................................24 3.7 Loss of Parkin promotes fragmented mitochondria to aggregate in deficiency of mitofusin................................................................................................................24 IV. DISSCUSION...........................................................................................................27 4.1 PINK1 might have several different function to regulate mitochondria in Parkin- independent pathway…………………...………...........………………………...28 4.2 Loss of Miro1 may be an initial step of mitophagy which promotes generating of mitochondrial buddings.........................................................................................29 4.3 Mitofusin is not the only Parkin substrate which regulate mitochondrial aggregation..........................................................................................................30 V. FIGURES...................................................................................................................31 5.1 Designing an integration line to investigate the relationship between mitochondria and neuronal morphology in PVD neuron..............................................................31 5.2 Mitochondrial localization affects dendritic growth and branching........................33 5.3 Not only localization, mitochondrial dynamics also affect dendritic morphogenesis………………………...............………….......….........................36 5.4 Mitochondria stabilize 2° dendritic growth............................................................38 5.5 Many small and blurred mitochondria occurred in axon in deficiency of Parkin.....................................................................................................................41 5.6 Loss of Parkin promotes fragmented mitochondria to aggregate in deficiency of mitofusin................................................................................................................45 5.7 Observation of mitochondria in cell body...............................................................48 5.8 Observation of neuronal morphology.....................................................................53 VI. REFFERENCES......................................................................................................57 VII. APPENDIX.............................................................................................................66 7.1 Constructs and transgenic worms...........................................................................66 7.2 Primers for genotyping...........................................................................................69 7.3 Images for quantification........................................................................................71 | - |
| dc.language.iso | en | - |
| dc.subject | E3泛素連接? | zh_TW |
| dc.subject | PTEN-誘導激?1 | zh_TW |
| dc.subject | 樹突型態 | zh_TW |
| dc.subject | 帕金森氏症 | zh_TW |
| dc.subject | 神經退化性疾病 | zh_TW |
| dc.subject | neurodegenerative diseases | en |
| dc.subject | Parkinsin’s disease | en |
| dc.subject | Parkin | en |
| dc.subject | dendritic morphogenesis | en |
| dc.subject | PINK1 | en |
| dc.title | 探討PINK1/Parkin如何影響粒線體動態與神經的發育 | zh_TW |
| dc.title | The role of PINK1/Parkin pathway in mitochondrial dynamics and neuronal morphogenesis | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 107-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 林敬哲;蔡欣祐 | zh_TW |
| dc.contributor.oralexamcommittee | Jing-Jer Lin;Hsin-Yue Tsai | en |
| dc.subject.keyword | 神經退化性疾病,帕金森氏症,樹突型態,PTEN-誘導激?1,E3泛素連接?, | zh_TW |
| dc.subject.keyword | neurodegenerative diseases,Parkinsin’s disease,dendritic morphogenesis,PINK1,Parkin, | en |
| dc.relation.page | 97 | - |
| dc.identifier.doi | 10.6342/NTU201900293 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2019-02-13 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | - |
| dc.date.embargo-lift | 2024-03-11 | - |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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