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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 | 張芳嘉(Fang-Chia Chang) | |
dc.contributor.author | Li-Ning Hsu | en |
dc.contributor.author | 徐莉寧 | zh_TW |
dc.date.accessioned | 2021-06-15T05:47:31Z | - |
dc.date.available | 2012-08-19 | |
dc.date.copyright | 2010-08-19 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-08-18 | |
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Drugs 65: 927-947, 2005. 69. Winokur A, Gary KA, Rodner S, Rae-Red C, Fernando AT, and Szuba MP. Depression, sleep physiology, and antidepressant drugs. Depress Anxiety 14: 19-28, 2001. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47098 | - |
dc.description.abstract | 傳統上以單胺類 (monoamine) 的失衡為憂鬱症的主因,而越來越多的報告表示,憂鬱症與腎上腺皮質軸 (hypothalamic-pituitary-adrenal axis, HPA axis) 失調具有不可忽視的相關性,環境中過度緊迫 (stressor) 導致corticotropin-releasing hormone (CRH) 升高,使個體出現憂鬱傾向,也符合了一般認知,壓力與憂鬱症密不可分的關係。CRH除了反映個體面對緊迫的正常生理機制,同時也是調控睡眠的重要因子,促進清醒的作用已廣為認同。CRH同時具備影響睡眠以及誘導憂鬱傾向之特性,似乎呼應了臨床上睡眠障礙 (sleep disturbances) 與憂鬱症之高共病性與相關性。我們假設憂鬱傾向和睡眠障礙由CRH共同媒介,以緊迫誘導的懸尾試驗 (tail suspension test, TST) 作為憂鬱模式,懸尾期間之移動距離 (moved distance) 評估大鼠之積極脫逃意圖、EEG (electroencephalogram) 判定睡眠狀態,並分為短期懸尾模式 (TST day1) 和長期懸尾模式 (TST day8),分別檢視CRH之作用。
短期懸尾模式和長期懸尾模式均無法觀察到典型的憂鬱症患者睡眠特徵。大鼠經過第 1天的懸尾,睡眠變化為NREM sleep與REM sleep於亮期 (light period) 減少、於暗期 (dark period) 增加,此現象可以HPA axis活性增加來解釋,並可用CRH receptor antagonist,astressin來阻斷。Astressin同時可增加懸尾時大鼠之掙扎運動,酵素結合免疫吸附試驗 (ELISA) 結果亦有HPA axis活性增加,表示在短期懸尾模式中,大鼠受到緊迫確實誘發了CRH增加,而同時媒介了睡眠改變和憂鬱傾向。在連續懸尾之下,睡眠變化趨緩,至懸尾第八日睡眠變化已幾近消失。行為上大鼠漸進性的增加絕望行為,但無法由astressin或是典型selective serotonin reuptake inhibitor (SSRI) 反轉,長期懸尾模式中睡眠和行為表現非同步變化,血清學可見HPA axis活化,卻不見CRH作用於睡眠及行為之證據。詳細機制仍待進一步研究。 | zh_TW |
dc.description.abstract | Since hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis is common among depression patients, corticotropin-releasing hormone (CRH) and its character in spontaneous sleep modulation are thought to be related to the depression-induced sleep disturbances. In present study, we proposed that CRH plays a role in sleep disruption in depressive rats. We used tail suspension test (TST) as a stress-induced depression model, which included short-term stress group (TST day1) and long-term stress group (TST day8), to investigate the effects of CRH. Behavior of learning helplessness, one major indication of depression in animal, was evaluated during the TST.
In the first day after TST, both NREM sleep and REM sleep significantly decreased in the light period, and increased during the dark period. As TST continuously performed, sleep alterations gradually diminished while behavioral despair was progressively observed. By intracerebroventricular (ICV) injection of the CRH receptor antagonist, astressin, prior to the TST in the first day, we found that blocking CRH increased the struggling behavioral during TST and reversed the sleep alterations caused by short-term TST, indicating the involvement of CRH in short-term TST. ELISA results of corticosterone had shown the hyperactivity of HPA axis in rats suffered both from short-term and long-term TST. However, the behavioral despair in rats suffered from long-term TST was neither reversed by astressin nor by typical SSRI, fluoxetine. We also found that astressin had no effect on long-term TST-induced sleep alterations, while fluoxetine had shown slightly suppression of REM sleep during the light period. This observation is consistent with the effect of typical antidepressants. These results suggest that CRH may participate in the initiation of stressed behavior and the consequent sleep alterations but is not dominant in maintenance phase. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T05:47:31Z (GMT). No. of bitstreams: 1 ntu-99-R97629026-1.pdf: 3725518 bytes, checksum: e5b9518429be018a4f6e421608b8fe18 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 目錄
圖目錄 V 中文摘要 VII 英文摘要 IX 壹、 實驗背景與文獻回顧 1 憂鬱症與睡眠失調 1 憂鬱症-內在因及外在因 2 1. CRH (corticotropin-realeasing hormone) 影響血清素之證據 3 2. 邊緣系統 —腎上腺皮質軸之交互作用 (Limbic-HPA axis interactions) 3 3. 神滋經養物質失調 4 憂鬱傾向下之睡眠變化 5 抗憂鬱藥物對於睡眠之影響 6 憂鬱症之動物模式 8 習得無助理論 8 研究動機與假設 10 貳、 材料與方法 12 一、 實驗動物 12 1. 手術 12 2. 裝置電腦波電極 (Electroencephalogram electrodes ; EEG) 12 3. 側腦室導管 (Intracerebroventricular cannulae ; ICV) 12 4. 術後照顧與適應 (habituation) 13 二、 憂鬱症模式 13 三、 實驗用藥 13 四、 實驗設計 14 1. 睡眠紀錄 14 2. 樣本採取 14 五、 睡眠分析:EEG腦波紀錄 15 六、 行為分析:EthoVision® 行為分析軟體 16 七、 酵素結合免疫吸附試驗 (Enzyme-linked immunosorbent assay ; ELISA) 16 1. CRH: 16 2. Corticosterone: 17 八、 統計學分析 17 參、 實驗結果 18 一、 短期懸尾模式 (TST day1) 18 1. 睡眠百分比值變化: 18 2. 睡眠結構: 18 二、 長期懸尾模式 (TST day8) 19 1. 睡眠百分比值變化: 19 2. 睡眠結構: 19 3. 移動距離: 20 三、 Astressin應用於懸尾模式 20 1 .短期懸尾模式 (TST day1): 20 2 .長期懸尾模式 (TST day8): 21 四、 Fluoxetine應用於懸尾模式 22 1. 長期懸尾模式 (TST day8): 22 五、 ELISA結果 23 1. CRH: 23 2. Corticosterone: 23 肆、 討論 24 以短期懸尾模式為例 (TST day1) 24 以長期懸尾模式為例 (TST day8) 25 CRH之作用 26 Fluoxetine之作用 27 檢討與展望 28 伍、 結論 32 陸、 參考文獻 49 柒、 附錄 58 | |
dc.language.iso | zh-TW | |
dc.title | Corticotropin - Releasing Hormone (CRH) 在懸尾模式誘發睡眠改變所扮演的角色 | zh_TW |
dc.title | The Role of Corticotropin - Releasing Hormone (CRH) in the Tail Suspension Test (TST) - induced
Sleep Alterations | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 李立仁,黃玉書,詹東榮,羅孝穗 | |
dc.subject.keyword | corticotropin - releasing hormone (CRH),憂鬱模式,懸尾試驗,睡眠,fluoxetine, | zh_TW |
dc.subject.keyword | corticotropin - releasing hormone (CRH),depression model,tail suspension test,fluoxetine, | en |
dc.relation.page | 59 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-08-19 | |
dc.contributor.author-college | 獸醫專業學院 | zh_TW |
dc.contributor.author-dept | 獸醫學研究所 | zh_TW |
顯示於系所單位: | 獸醫學系 |
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