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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉宏輝 | |
| dc.contributor.author | Ju-Hsuan Hsu | en |
| dc.contributor.author | 許茹絢 | zh_TW |
| dc.date.accessioned | 2021-06-17T02:42:57Z | - |
| dc.date.available | 2017-09-13 | |
| dc.date.copyright | 2017-09-13 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-16 | |
| dc.identifier.citation | Bading, H., G. E. Hardingham, C. M. Johnson and S. Chawla (1997). 'Gene regulation by nuclear and cytoplasmic calcium signals.' Biochem Biophys Res Commun 236(3): 541-543.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68935 | - |
| dc.description.abstract | 神經幹細胞（NSCs）以及神經前驅細胞（NPCs）是有自我更新能力（self-renewal）和分裂能力的細胞。神經幹細胞的分化主要有三種型態，分別是神經細胞(neuron)、星狀膠細胞(astrocyte)或寡突細胞(oligodendrocyte)。神經幹細胞分化過程主要是受到轉錄因子或是生長因子的調控，目前已有相關研究發現這個過程中，鈣離子會參與並影響基因轉錄的調控表現。在神經幹細胞分化過程中也發現，活化鈣離子通道或者是影響鈣離子通道的表現，會使神經幹細胞分化命運的改變。而在過去的研究中也顯示calcium transients會使未分化的神經細胞較有能力分化成神經細胞。因此在本實驗中，利用C57BL/6小鼠進行體外幹細胞球培養，再利用fura-2來觀察並分析其分化期間的細胞內鈣離子濃度變化以及calcium transients的三個parameter變化，探討細胞內鈣離子濃度和calcium transients在神經細胞和星狀膠細胞的不同。實驗結果顯示神經細胞內的鈣離子濃度較高，calcium transients的特色為amplitude和AUC較高，星狀膠細胞內鈣離子濃度較低，calcium transients的特色為amplitude和AUC較低。為了瞭解細胞內鈣離子濃度和calcium transient是否會影響神經幹細胞的命運，我們使用藥物EGTA/AM在分化期間加入減少細胞內的鈣離子濃度來觀察是否會影響到神經幹細胞的分化命運。實驗結果顯示，降低細胞內鈣離子濃度以及降低amplitude，會使神經幹細胞的分化命運走向星狀膠細胞，而且影響的時間點為分化前四天。同時我們也使用另一種不同機轉藥物來驗證這個結果，我們使用ryanodine receptor抑制劑ruthenium Red來觀察神經幹細胞的分化命運，實驗結果顯示相同，ruthenium Red會使神經幹細胞分化走往星狀膠細胞的命運，顯示影響細胞內的鈣離子濃度高低以及影響calcium transients的amplitude會影響神經幹細胞分化命運，同時也代表鈣離子在神經幹細胞分化的過程中扮演著重要的角色。 | zh_TW |
| dc.description.abstract | Neural stem cells (NSCs) and neural progenitor cells (NPCs) are multipotent cells which have the capacity for self-renewal and differentiation into neurons, astrocytes and oligodendrocytes in the mammalian central nervous system. Maturation of NSCs is known to be regulated by both cell intrinsic and extrinsic factors. In the present study, we used primary neural stem cell culture from C57BL/6 newborn mice to study the calcium level and calcium transients in neurogenesis cell fate determination. We found the basal calcium level of neuron was higher than astrocyte. Moreover, we also found that the calcium transients amplitude of neuron was higher than astrocyte. To define the critical time window of calcium transient that is required for NSCs fate determination, we used the Ca2+ chelator EGTA-AM to reduce the intracellular Ca2+ concentration [Ca2+]i at different time point after differentiation induction. Our results showed that inhibition of [Ca2+]i within 4 days after seeding caused the NSCs tended toward a glial lineage. Furthermore, blocking ryanodine receptor by ruthenium red also caused the NSCs differentiation tended toward a glial lineage. These results indicated that the intracellular calcium level and amplitude may play an important role in NSCs fate determination during the neurogenesis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T02:42:57Z (GMT). No. of bitstreams: 1 ntu-106-R04443015-1.pdf: 2549586 bytes, checksum: 0ddbbe96d4cdb4167635f30ae9fe8109 (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 目錄
摘要 I Abstract III 第一章 緒論(Introduction) 1 第一節 神經幹細胞的神經新生 1 第二節 鈣離子參與在生長因子和轉錄因子調控神經幹細胞的分化 1 第三節 鈣離子通道活化及表現對神經幹細胞的分化影響 3 第四節 Calcium transients影響神經分化過程 4 第五節 Calcium transients在老鼠神經發育中的角色 5 第六節 研究動機與目的 6 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 神經幹細胞培養 8 第三節 神經幹細胞分化 9 第四節 Fura-2/AM偵測胞內鈣離子 10 第五節 免疫細胞染色法（Immunocytochemistry） 11 第六節 細胞座標對應 11 第七節 過濾雜訊方式 12 第八節 分析訊號 12 第九節 實驗藥品 12 第十節 MTT試驗 12 第十一節 統計分析 13 第三章 結果（Result） 14 第一節 分化期間calcium transients在神經細胞和星狀膠細胞的特色 14 第二節 藉由EGTA/AM改變細胞內鈣離子濃度和calcium transients 15 第三節 藉由抑制ryanodine receptor改變細胞內鈣離子濃度和calcium transient 16 第四節 利用thapsigargin改變細胞內鈣離子濃度和calcium transients 18 第四章 討論（Discussion） 20 第一節 總述 20 第二節 神經細胞和星狀膠細胞內的鈣離子濃度不同 20 第三節 細胞內鈣離子濃度影響細胞的命運分化之可能機轉 21 第四節 其他影響分化的可能機轉 22 第五節 未來展望 23 第五章 圖表（Figures） 24 第六章 附錄 51 第一節 免疫細胞染色的抗體 51 第二節 實驗流程 52 第三節 MTT assay of thapsigargin 1nM 54 第四節 分析程式表 55 1. 分析細胞fura-2訊號 55 2. 分析每顆細胞的fura-2 ratio及細胞座標 64 3. 分析fura-2訊號之量化calcium transients參數 66 參考文獻（References） 72 | |
| dc.language.iso | zh-TW | |
| dc.subject | 神經幹細胞 | zh_TW |
| dc.subject | 分化 | zh_TW |
| dc.subject | 細胞分化命運 | zh_TW |
| dc.subject | 鈣離子濃度 | zh_TW |
| dc.subject | 鈣離子 | zh_TW |
| dc.subject | differentiation | en |
| dc.subject | neural stem cell | en |
| dc.subject | calcium transients | en |
| dc.subject | calcium level | en |
| dc.subject | cell fate determination | en |
| dc.title | 鈣離子在神經幹細胞分化過程中的角色 | zh_TW |
| dc.title | Role of Ca2+ in the neural stem cell differentiation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 蔡丰喬 | |
| dc.contributor.oralexamcommittee | 林琬琬,符文美 | |
| dc.subject.keyword | 神經幹細胞,分化,細胞分化命運,鈣離子濃度,鈣離子, | zh_TW |
| dc.subject.keyword | neural stem cell,differentiation,cell fate determination,calcium level,calcium transients, | en |
| dc.relation.page | 77 | |
| dc.identifier.doi | 10.6342/NTU201703202 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-16 | |
| 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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