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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳俊宏(Chun-Hong Chen) | |
dc.contributor.author | Yen-Wei Lai | en |
dc.contributor.author | 賴彥瑋 | zh_TW |
dc.date.accessioned | 2021-06-15T16:30:07Z | - |
dc.date.available | 2019-08-28 | |
dc.date.copyright | 2015-08-28 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-08-13 | |
dc.identifier.citation | Agostini, M., Tucci, P., Killick, R., Candi, E., Sayan, B.S., Rivetti di Val Cervo, P., Nicotera, P., McKeon, F., Knight, R.A., Mak, T.W., et al. (2011). Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets. Proceedings of the National Academy of Sciences of the United States of America 108, 21093-21098.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52841 | - |
dc.description.abstract | 神經退化 (neurodegeneration) 的機制可能是藉由不正常的蛋白質堆積和/或壓力引起的細胞死亡 (cell death) 所造成的。可是,在昆蟲的變態過程中細胞死亡會自然地發生以去調節神經的完整性,透過神經再塑性 (neural remodeling) 的其中一個機制叫作計畫性的細胞死亡 (programmed cell death)。目前尚未清楚神經再塑性和神經退化是否可能經由類似的調控機制去決定神經細胞的命運,另外一個神經再塑性的例子就是果蠅的 gamma 神經元的修剪 (gamma neuron pruning)。
在果蠅的蘑菇體 (mushroom body) 中,包含了三種不同形式的神經元:gamma、alpha'/beta' 和 alpha/beta,它們掌管了果蠅的學習與記憶。當果蠅進入蟲蛹的階段時, gamma神經元的軸突 (axons) 與樹突 (dendrites) 進行修剪與重新生長,以便在成蟲時期產生新的神經網絡,而這個過程是受到TGF-beta 訊息傳遞以及類固醇賀爾蒙:ecdysone訊息傳遞 (TGF-beta signaling and steroid hormone ecdysone signaling) 所調控的。另外,軸突與樹突的修剪只發生在昆蟲的變態過程中並不會發生在成蟲階段。然而,TGF-beta 訊息傳遞以及類固醇賀爾蒙:ecdysone訊息傳遞共同協調 gamma神經元在精確的時間下進行修剪,依然尚未清楚。 先前的一篇研究指出果蠅的miR-34主要表現在果蠅成蟲的腦中,而且對於神經退化性以及壽命 (life span) 的調控扮演著重要的角色,miR-34被指出說它會降低 E74基因的表現量。在miR-34突變之下加速果蠅腦神經退化性的發生,這顯示出miR-34扮演著不可缺少的角色去減少神經細胞的死亡以便延緩腦部老化的現象發生。在這裡,我們將miR-34提早表現在果蠅神經發育時期的蘑菇體,觀察到 gamma 神經元的修剪被抑制住,因而提供了一個線索對於神經修剪與miR-34彼此間可能的分子連結,所以推測神經再塑性與神經退化的之間的連結可能是透過類似的機制而調控的,並且受到miR-34的阻擋。我們進一步證實miR-34 造成EcR-B1的表現量下降,可能是藉由抑制調控EcR-B1表現量的上游基因所導致的結果,再引入 EcR-B1 可以挽救miR-34所產生的神經元修剪的缺陷。miR-34的結合對象包括E74、Yem-alpha和Hr4都不是調控 gamma 神經元的修剪,可是miR-34可能調控TGF-beta 訊息傳遞將成為未來實驗上的一個新的方向。 最後,本篇研究提供了一個新方向,探討果蠅的miRNA在不同時期的表現量有所不同,以去調節神經退化性和神經再塑性之間的平衡。 | zh_TW |
dc.description.abstract | The mechanisms of neurodegeneration may go through abnormal protein aggregation and/or stress-induced cell death. Yet, cell death is occurred during insect metamorphosis to modulate neural integrity by programmed cell death (PCD) that is one of neural remodeling. It is unclear whether neural remodeling and neurodegeneration may share similar mechanisms to determine neuron cell fate. Another neural remodeling mode is Drosophila gamma neuron pruning.
The Drosophila mushroom bodies (MB) composed of three different types of neurons: gamma, alpha'/beta' and alpha/beta regulate the learning and memory. During the pupal formation, gamma axons and dendrites are pruned and regrow to establish the new neural network in adult stage. This process is controlled by TGF-beta signaling and steroid hormone ecdysone signaling. This axon and dendrite pruning process is only held during metamorphosis but not in adult stage. However, how TGF-beta and steroid hormone ecdysone signaling to be coordinated the precise timing of gamma neuron pruning is still elusive. A previous study showed that Drosophila miR-34 is mainly expressed in the brain during adult stage and plays an important role in neurodegeneration and life span by downregulating E74. miR-34 mutant flies showed accelerated neurodegeneration phenotype in the adult brain. It implies the important role of miR-34 to mitigate brain aging through decreasing neuron cell death. Here we report up-regulation of miR-34 in MB during neural developmental stage suppresses gamma neuron pruning in Drosophila MB, providing a possible molecular link between neural pruning and miR-34. It is suggested that the link between neural remodeling and neurodegeneration is regulated through similar machinery which is blocked by miR-34. We further demonstrated that miR-34 downregulating ecdysone receptor-B1 (EcR-B1) results in pruning defect and suggested that miR-34 knockdowns upstream genes which regulate EcR-B1 expression. Reintroduction of EcR-B1 can rescue this pruning defect caused by overexpression of miR-34. The E74, Yem-alpha and Hr4, which are targets of miR-34 are not key factors to regulate gamma neuron pruning but a new direction reveals miR-34 may regulate TGF-beta signaling. This study raises a new research direction that different miRNA expression level in distinct stages may regulate the balance between neurodegeneration and neural remodeling. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T16:30:07Z (GMT). No. of bitstreams: 1 ntu-104-R01b43022-1.pdf: 2055757 bytes, checksum: cd2634a1de3b0884034f26404a651fc4 (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | 口試委員會審定書 1
致謝 2 ABBREVIATIONS 3 中文摘要 4 ABSTRACT 6 TABLE of CONTENTS 8 TABLE of FIGURES 10 INTRODUCTIONS 12 1. miRNAs 12 1.1 The relationship of miRNAs, aging and neurodegeneration 13 1.2 Drosophila miR-34 15 2. Drosophila mushroom body 15 3. Neural remodelong 16 3.1 gamma neuron pruning in mushroom body 17 4. The purpose of this thesis 19 MATERIALS and METHODS 20 1. Flies stocks 20 2. Induction of mosaic analysis with a repressible cell marker 21 3. Immunostaining 21 4. Immunoblot (western blot) 22 RESULTS 24 1. Enforced miR-34 overexpression abolishes gamma neuron pruning in the mushroom body 24 2. miR-34 generates the defect phenotype of gamma neuron pruning in differentiated stage 25 3. miR-34 overexpression decreases endogenous EcR-B1 expression and restoring EcR-B1 expression can rescue gamma neuron pruning defect 26 4. E74, Hr4 and Yem-alpha, as miR-34 targets, do not involve in gamma neuron pruning but miR-34 may regulate TGF-beta signaling. 27 DISCUSSIONS and CONCLUSIONS 29 1. Regulation of miR-34 expression in adult brains 29 2. The role of miR-34 regulating neurodegeneration and neural development 30 3. The function of miR-34 compared Drosophila miR-34 to mammalian miR-34. 32 REFERENCES 35 FIGURES 50 | |
dc.language.iso | en | |
dc.title | 果蠅微小核醣核酸-34 的大量表現造成蘑菇體伽馬神經元的神經修剪的缺失 | zh_TW |
dc.title | Drosophila miR-34 overexpression results in neural pruning defect of mushroom body neurons | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 游宏祥(Hung-Hsiang Yu) | |
dc.contributor.oralexamcommittee | 孫以瀚(Y. Henry Sun),高智飛(Chih-Fei Kao) | |
dc.subject.keyword | 黃果蠅,微小核醣核酸-34,神經退化,蘑菇體,gamma神經元的修剪, | zh_TW |
dc.subject.keyword | Drosophila melanogaster,miR-34,neurodegeneration,mushroom body,gamma neuron pruning, | en |
dc.relation.page | 62 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2015-08-13 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
顯示於系所單位: | 分子與細胞生物學研究所 |
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