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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳小梨(Show-Li Chen) | |
| dc.contributor.author | Hao-Yu Lu | en |
| dc.contributor.author | 呂晧瑜 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:27:33Z | - |
| dc.date.available | 2022-08-31 | |
| dc.date.available | 2022-11-24T03:27:33Z | - |
| dc.date.copyright | 2021-09-16 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-26 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81040 | - |
| dc.description.abstract | BCAS2，也稱為pre-mRNA 剪接因子 (SPF27)，是一種大小為 26 kDa 的核蛋白，也是 hprp19 複合物的核心成分。 BCAS2參與pre-mRNA剪接，對細胞生長調控有很大影響。本實驗室先前的研究發現，BCAS2會參與DNA損傷修復和果蠅翅膀的發育，並且可以調節β-catenin pre-mRNA的剪接，本實驗室發現， CaMKIIα 驅動的 BCAS2 cKO 小鼠中的 β-catenin 表現量會降低。 有關β-catenin在神經元樹突生長中的調控已有大量文獻記載。在 BCAS2 cKO 小鼠中，我們觀察到 Ki67+ 細胞數量減少。Ki67 是一種常用的增殖標誌蛋白，這表明缺乏 BCAS2 可能會影響小鼠成年海馬迴神經新生。依據我們實驗室尚未發表的數據結果，透過 AAV-BCAS2 腦內注射增加 β-catenin的表現將改善 BCAS2 cKO 小鼠神經的樹突生長和學習行為測試的表現。因此，為了探究AAV target的細胞類型，我們在 WT 小鼠中進行了 AAV-DJ8 GFP 和 AAV-9 GFP 的顱內注射。結果表明，AAV 不僅可以target神經幹細胞和未成熟神經元，還可以target非神經元細胞，如星形膠質細胞和中間神經元。這些結果表示 AAV-BCAS2 可以透過自autonomous和non-autonomous effect調節神經發生。此外，我們想研究 AAV-BCAS2 是否會對 BCAS2 cKO 小鼠和阿茲海默疾病模式小鼠(APP)產生治療作用。結果表明，AAV-BCAS2 可以成功增加 cKO/BCAS2 小鼠中 Ki67+ 細胞的數量。在 APP 小鼠中，與 APP/GFP 對照小鼠相比，AAV-BCAS2 顱內注射還增加了 Ki67+ 和 DCX+ 細胞的數量。此外，與 APP/GFP 對照組相比，AAV-BCAS2 增加了 APP/BCAS2 小鼠中 β-catenin 蛋白的表現。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:27:33Z (GMT). No. of bitstreams: 1 U0001-2408202116183000.pdf: 18698042 bytes, checksum: 16bdd264702ad0f9b4a353e6f293de0c (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試委員審定書 i 致謝 ii 中文摘要 iii ABSTRACT iv TABLE OF CONTENT vi CHAPTER 1 INTRODUCTION 1 1.1 The characteristic of BCAS2 1 1.2 Canonical Wnt/ β-catenin signaling pathway 3 1.3 Adult hippocampal neurogenesis 4 1.4 Wnt/β-catenin pathway in adult hippocampal neurogenesis 6 1.5 Astrocytes and interneurons in adult hippocampal neurogenesis 8 1.6 Alzheimer’s disease 15 1.7 AimS of this study 17 CHAPTER 2 MATERIALS AND METHODS 18 2.1 Mice cohorts 18 2.2 Western blot analysis 18 2.3 Brain stereotaxic surgery 19 2.4 Tissue preparation 20 2.5 Immunohistochemistry 20 2.6 Stereological analysis 21 2.7 Statistical analysis 22 CHAPTER 3 RESULTS 23 3.1 The reduced number of Ki67+ proliferative cells in SGZ of BCAS2 cKO mice. 23 3.2 Cell proliferation reduced in hippocampus after BCAS2 knockdown. 24 3.3 AAV DJ8 virus could efficiently infect into neural stem cells, immature neurons, astrocytes and interneurons.. 26 3.4 Intracranial hippocampal injection of AAV-BCAS2 could restore cell proliferation in 8-week-old BCAS2 cKO mice. 27 3.5 AAV 9 virus could efficiently infect into neural stem cells, immature neurons, astrocytes and interneurons.. 28 3.6 Intracranial hippocampal injection of AAV-BCAS2 could rescue cell proliferation and increase the number of new born neurons in 4-month-old APP mice. 29 3.7 Intracranial hippocampal injection of AAV-DJ8-BCAS2 in APP mice rescued adult neurogenesis through β-catenin expression 31 CHAPTER 4 DISCUSSION 33 REFERENCE 44 FIGURES 53 SUPPLEMENTARY 67" | |
| dc.language.iso | en | |
| dc.subject | BCAS2 | zh_TW |
| dc.subject | β-catenin | zh_TW |
| dc.subject | BCAS2條件式基因剔除小鼠(CAMKIIα-Cre；BCAS2flox/flox) | zh_TW |
| dc.subject | 阿茲海默症 | zh_TW |
| dc.subject | APP J20阿茲海默症疾病模式小鼠 | zh_TW |
| dc.subject | 神經新生 | zh_TW |
| dc.subject | APP J20 mice | en |
| dc.subject | adult neurogenesis | en |
| dc.subject | BCAS2 | en |
| dc.subject | β-catenin | en |
| dc.subject | BCAS2 cKO mice (CAMKIIα-Cre；BCAS2flox/flox) | en |
| dc.subject | Alzheimer's disease | en |
| dc.title | AAV-BCAS2 在條件式剔除小鼠及阿茲海默症疾病模式小鼠中的治療效果 | zh_TW |
| dc.title | The therapeutic effect of AAV-BCAS2 in BCAS2 cKO and Alzheimer's disease model mice | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃祥博(Hsin-Tsai Liu),鄭菡若(Chih-Yang Tseng),黃憲松 | |
| dc.subject.keyword | 神經新生,BCAS2,β-catenin,BCAS2條件式基因剔除小鼠(CAMKIIα-Cre；BCAS2flox/flox),阿茲海默症,APP J20阿茲海默症疾病模式小鼠, | zh_TW |
| dc.subject.keyword | adult neurogenesis,BCAS2,β-catenin,BCAS2 cKO mice (CAMKIIα-Cre；BCAS2flox/flox),Alzheimer's disease,APP J20 mice, | en |
| dc.relation.page | 85 | |
| dc.identifier.doi | 10.6342/NTU202102685 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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