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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 胡孟君(Meng-Chun Hu) | |
dc.contributor.author | Szu-Ying Liu | en |
dc.contributor.author | 劉思穎 | zh_TW |
dc.date.accessioned | 2021-06-16T06:48:38Z | - |
dc.date.available | 2020-07-24 | |
dc.date.copyright | 2014-10-09 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-07-24 | |
dc.identifier.citation | Abraham, N. M., V. Egger, D. R. Shimshek, R. Renden, I. Fukunaga et al., 2010 Synaptic inhibition in the olfactory bulb accelerates odor discrimination in mice. Neuron 65: 399-411.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57496 | - |
dc.description.abstract | P450膽固醇側鏈截切酶 (cytochrome P450 side chain cleavage, P450scc) 為CYP11A1基因的產物,參與類固醇生成的關鍵步驟,能將膽固醇轉換為Pregnenolone,主要表現在腎上腺及性腺。CYP11A1也表現在腦中,控制神經類固醇的生成,並對腦的生理功能有所影響。由於腦中CYP11A1表現量很低,因此目前對於CYP11A1表現分布及轉錄調控尚未明瞭。本實驗室以CYP11A1啟動子驅動Cre重組酶,建立SCCmtp-Cre基因轉殖鼠,以Cre的表現探討CYP11A1啟動子在類固醇生成組織的轉錄活性。本論文利用SCCmtp-Cre與ROSAR-Td-tomato小鼠交配,分析螢光蛋白在腦的表現,以了解內生性CYP11A1可能的表現分布。我觀察到Td-tomato在腦中許多區域都有表現,包括間腦、下視丘、杏仁核以及嗅覺系統的嗅球與嗅覺上皮。我們發現Td-tomato會專一地表現在嗅球的granule cell layer (GCL),且較集中於內層。這些有螢光表現之細胞,其神經纖維會延伸至mitral cell layer (MCL) 與external plexiform layer (EPL),符合granule cells的特性。免疫螢光染色分析顯示,Td-tomato螢光細胞可表現神經元的標誌蛋白NeuN,但沒有星狀細胞的標誌蛋白GFAP之表現,說明其為分化的神經元。GCL由granule cells組成,會分泌γ-aminobutyric acid (GABA) 為神經傳導物。以GABA的生成酵素glutamic acid decarboxylase 67 (GAD67)、glutamic acid decarboxylase 65 (GAD65) 進行染色,結果發現Td-tomato螢光細胞幾乎都有這兩者的表現。有些granule cells會表現鈣離子結合蛋白calretinin或calbindin,但這兩者都沒有表現在Td-tomato螢光細胞。
我們利用Cyp11a1基因剔除鼠 (KO) 進一步探討Cyp11a1在嗅球的生理功能。Western blot分析顯示,KO中GAD65蛋白質量顯著下降,而GAD67量沒有統計差異。相反地,calretinin量在KO顯著上升,而calbindin量則沒有差異。存在於glomerular layer的蛋白olfactory marker protein (OMP),在KO的表現量也顯著上升。利用TUNEL assay觀察Cyp11a1基因剔除對細胞凋亡的影響,結果發現KO在GCL的細胞凋亡數目顯著多於野生型。這些結果說明,Cyp11a1基因在嗅球可能扮演重要功能。 | zh_TW |
dc.description.abstract | CYP11A1 encodes cholesterol side-chain cleavage enzyme (P450scc). P450scc converts cholesterone into pregnenolone, which is the key step of steroid biosynthesis. CYP11A1 is abundantly expressed in the adrenal glands and gonads. In addition, it is also expressed in the brain to control the synthesis of neurosteroids that are involved in many neural functions. Because the amount of endogenous mRNA of Cyp11a1 is very low, the expression of CYP11A1 gene in the brain has not been well characterized. We previously generated a SCCmtp-Cre transgenic mouse line in which the expression of Cre recombinase gene is under the control of human CYP11A1 promoter. To study the expression of SCC promoter activity in the brain, SCCmtp-Cre was crossed to ROSA26R Cre-dependent Td-Tomato reporter mice. Td-tomato signal was found in several brain areas including the olfactory system (olfactory bulb and olfactory epithelium), diencephalon, hypothalamus, and amygdala. In the olfactory bulb, Td-tomato signal is specifically present in the granule cell layer. We can see the process of Td-tomato extend into mitral cell layer and external plexiform layer. Immunofluoresence analysis showed that Td-tomato are NeuN-positive (neuron marker) and GFAP-negative (astrocyte marker), indicating that these cells are differentiated neurons. Granule cells release γ-aminobutyric acid (GABA) which is synthesized by glutamic acid decarboxylase 65 (GAD65) or 67 (GAD67). Our data showed that most of Td-tomato cells co-localized with these two enzymes. Some granule cells express calcium binding protein calretinin or calbindin. However, these two markers were not co-localized with Td-tomato signal.
We used Cyp11a1 knockout mice (KO) to explore the function of Cyp11a1 in the olfactory bulb. Western blot analysis showed that the protein levels of GAD 65, but not GAD67 are significantly decreased in KO mice. In contrast, the protein levels of calretinin, but not calbindin are significantly increased in KO mice. Olfactory marker protein in glomerulus is also significantly increased in KO mice. In addition, TUNEL assays showed that KO mice have more apoptotic cells in GCL compared to wild-type mice. These results suggested that Cyp11a1 may play a critical role in the olfactory bulb. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T06:48:38Z (GMT). No. of bitstreams: 1 ntu-103-R01441012-1.pdf: 1697047 bytes, checksum: ade0c62f00684a3cd7f6f1f8c7a5439d (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 誌謝 I
目錄 III 表次 V 圖次 V 中文摘要 VI Abstract VIII 第一章 導論 1 一、類固醇荷爾蒙之生成 1 二、神經類固醇 1 1. 神經類固醇之發現 1 2. 神經類固醇之作用方式與功能 2 三、Cyp11a1基因在腦部的表現 3 1. Cyp11a1於神經系統內分布 3 2. 人類CYP11A1啟動子於神經系統的調控 4 四、嗅覺系統 5 1. 構造與神經迴路 6 2. 嗅覺系統的神經元新生 (neurogenesis) 與凋亡 (apoptosis) 7 五、研究目的 9 第二章 材料與方法 11 一、基因轉殖鼠之產生 11 二、小鼠基因型檢測 11 三、灌流 13 四、冷凍組織切片 13 五、嗅球與嗅覺上皮之total RNA萃取 14 六、反轉錄-聚合酵素鏈鎖反應 14 七、免疫組織螢光染色 15 八、西方墨點法 16 九、石蠟組織切片 17 十、嗅球細胞凋亡之分析 17 十一、統計分析 18 第三章 結果 19 一、SCCmtP-Cre轉殖基因於腦中表現 19 二、內生性Cyp11a1 mRNA於嗅覺系統表現 20 三、SCCmtP-Cre轉殖基因於嗅球的表現分布 20 四、SCCmtP-Cre轉殖基因於嗅球表現的細胞型態 21 1. NeuN 21 2. GFAP 21 3. GAD67、GAD65 21 4. Calretinin 22 5. Calbindin 22 五、Cyp11a1基因剔除對嗅球之影響 22 1. Cyp11a1基因剔除鼠之產生 22 2. Cyp11a1基因剔除對蛋白質表現之影響 23 3. Cyp11a1基因剔除對細胞凋亡之影響 23 第四章、討論 25 一、Cyp11a1於嗅球中表現 25 二、以SCCmtp-Cre/T小鼠螢光表現預測內生性Cyp11a1在腦內表現分布 25 1. Cre重組酶在不同轉殖鼠腦內表現結果一致 26 2. Cre重組酶在上視丘、視丘、下視丘與內生性Cyp11a1的分布結果相同 26 三、嗅球標誌蛋白 26 四、嗅球標誌蛋白的變化對於嗅球的影響 27 1. GAD表現量減少 27 2. Calretinin標誌蛋白表現量上升 28 3. OMP標誌蛋白表現量上升 29 五、嗅球細胞凋亡 29 Reference: 31 | |
dc.language.iso | zh-TW | |
dc.title | Cyp11a1基因在嗅球表現功能之探討 | zh_TW |
dc.title | Analysis of Cyp11a1 expression and function in olfactory bulb | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 李立仁,王慈蔚,周申如 | |
dc.subject.keyword | 嗅球, | zh_TW |
dc.subject.keyword | Cyp11a1,olfactory bulb, | en |
dc.relation.page | 57 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-07-24 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生理學研究所 | zh_TW |
顯示於系所單位: | 生理學科所 |
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