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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 劉宏輝(Horng-Huei Liou) | |
dc.contributor.author | Yun Hsu | en |
dc.contributor.author | 許筠 | zh_TW |
dc.date.accessioned | 2021-06-15T11:45:30Z | - |
dc.date.available | 2016-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-13 | |
dc.identifier.citation | Aguilar, V., and Fajas, L. (2010). Cycling through metabolism. EMBO Mol Med 2, 338-348.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49743 | - |
dc.description.abstract | 第一型電壓依賴型鈉離子通道(Nav1.1)出現異常時,會造成Dravet症候群這種嚴重的癲癇疾病,而癲癇被認為是由於異常的神經新生導致的。我們實驗室先前的研究利用SCN1A突變小鼠探討鈉離子通道對神經幹細胞發育的調控,而在其神經幹細胞球培養中,發現細胞的增生及分化能力都有增加的結果。細胞週期為影響細胞增生的重要因素之一,同時其中細胞週期中的S階段(S-phase)有縮短和G1階段(G1-phase)延長的改變則會影響細胞分化走向成熟神經細胞。因此在本實驗中,我們想要了解癲癇行為是否在SCN1A突變模型中幹細胞發育上有影響,因此利用有癲癇行為產生的六週大(6w)成鼠進行實驗,並利用兩種不同的DNA類似物(DNA analog)的標定,分析細胞週期的改變,並探討細胞週期對於神經新生的調控。我們發現SCN1A突變能造成海馬迴的齒迴中大量的神經新生,並伴隨S階段的縮短和G1階段的延長,並且發現這樣的細胞週期改變可能透過p27的表現下降和CDK2表現上升。由於這種細胞週期變化的模式,被認為會驅使神經幹細胞分化為成熟神經細胞,而我們實驗結果同樣顯示SCN1A突變促進神經幹細胞分化為神經細胞,並抑制其分化為星狀膠細胞。綜合以上結果,並配合文獻探討,認為SCN1A缺陷造成神經幹細胞內鈣離子濃度上升,抑制p27的作用,使CDK2表現上升,造成細胞週期進程改變,最終驅使神經幹細胞分化為神經細胞。 | zh_TW |
dc.description.abstract | The mutation of type I voltage-gated sodium channel (Nav1.1), encoding by SCN1A causes spontaneous seizure, cognitive impairment and autism-like behavior, indicating that sodium channel plays the important role in neuron development. According to our lab previous study, the enhanced proliferation activity and differentiation process in the neurosphere culture form SCN1A mutation. The highly proliferation activity usually is accompanied with the cell cycle process alternation. Among the cell cycle alternation, the prolonged S-phase and shortened G1-phase are the key point that promote neural stem cell differentiating into neuron. Here, we find the enhanced neurogenesis activity in SCN1A mutation in vivo. And the SCN1A mutation plays the role in prolonging S-phase and shortening G1-phase in the neural stem/ progenitor cell (NSC/NPC) itself, independent from seizure behavior. Under the alternation of cell cycle progress, the upregulation of cyclin-dependent kinase 2 (CDK2) and downregulation of p27, the cyclin-dependent kinase inhibitor (CDKi) are observed. Due to the possible role of p27 in modulating differentiation, we discover that NSC/NPC tend to differentiate into neurons but astrocytes in SCN1A mutation. These finding provide evidence that the mutation of sodium channel affects the NSC/NPC development by cell cycle alternation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T11:45:30Z (GMT). No. of bitstreams: 1 ntu-105-R03443009-1.pdf: 5583557 bytes, checksum: 944316709977c46103d5019acb1b23a8 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 摘要……………………………..……………………………..……………………..…II
Abstract…………………………………………………………………………………III 圖目錄…………………………………………………………………………………..V 第一章 緒論(Introduction)……………………………..……………………………..1 第一節 鈉離子通道……………………………..……………………………..…..1 第二節 鈉離子通道調控神經幹細胞發育……………………………..…………2 第三節 神經幹細胞發育與細胞週期的改變……………………………..……....4 第四節 細胞週期調控神經幹細胞發育……………………………..……………5 第五節 研究動機與目的……………………………………..……………………7 第二章 實驗材料與方法(Materials and Methods)…..…..…………………………8 第一節 實驗動物…………..…………………………..…………………………..8 第二節 毛果芸香鹼癲癇模型……………………………..………………………9 第三節 腦組織切片製備……………………………..……..……………………..9 第四節 免疫螢光染色……………………………………………………………10 第五節 細胞週期分析……………………………..……………………………..12 第六節 細胞週期離開指數分析…………………………………………………13 第七節 統計分析……………………………..……………………………..……14 第三章 結果(Result)………………………………………………………………….15 第一節 毛果芸香鹼引發癲癇導致神經幹細胞增生,並改變其細胞週期進…15 第二節 SCN1A突變造成神經幹細胞�前驅細胞大量增生……………………16 第三節 SCN1A突變造成神經幹細胞�前驅細胞的細胞週期中S階段時間縮短及G1階段時間延長……………………………..………………………17 第四節 SCN1A突變造成較多具有增生能力的神經幹細胞……………………18 第五節 SCN1A突變導致週期素激酶2(CDK2)表現量上升及週期素激酶抑制子p27表現量下降………………………………………………….………20 第六節 SCN1A突變導致神經幹細胞分化為神經細胞,而非星狀膠細胞……21 第四章 討論(Discussion)………………………..……………………………..……23 第一節 總述……………………………..………………………………..………23 第二節 SCN1A突變對於神經幹細胞與細胞週期的調控………………………23 第三節 p27對於神經幹細胞的調控……………………………..…………...…25 第四節 SCN1A突變於神經幹細胞分化的影響…………………………………26 第五節 細胞週期對於幹細胞發育的調控………………………………………27 第六節 結論及未來展望………………………..……………………………..…29 第五章 圖表(Figures)……………………………..………………………………….30 參考文獻……………………………..……………………………..………………….58 | |
dc.language.iso | zh-TW | |
dc.title | 細胞週期在SCN1A突變中對於神經幹細胞發育
之調控角色研究 | zh_TW |
dc.title | The Effect of Cell Cycle Regulation on Neural Stem Cell
Development in SCN1A Mutation | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 符文美(Wen-Mei Fu),林泰元(Thai-Yen Ling),李立仁(Li-Jen Lee) | |
dc.subject.keyword | Dravet症候群,Nav1.1,SCN1A,神經幹細胞,細胞週期,神經新生, | zh_TW |
dc.subject.keyword | Dravet syndrome,Nav1.1,SCN1A,neural stem cell,cell cycle,neurogenesis, | en |
dc.relation.page | 69 | |
dc.identifier.doi | 10.6342/NTU201602392 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥理學研究所 | zh_TW |
顯示於系所單位: | 藥理學科所 |
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