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系統識別號 U0026-2407201518215800
論文名稱(中文) 早期生活經驗對於壓力感受性與適應性的影響
論文名稱(英文) Early life experiences determine stress susceptibility and adaptation
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 103
學期 2
出版年 104
研究生(中文) 蕭詠名
研究生(英文) Young-Ming Hsiao
電子信箱 ckwin789@hotmail.com
學號 S26024044
學位類別 碩士
語文別 中文
論文頁數 63頁
口試委員 口試委員-姜學誠
口試委員-張雅雯
指導教授-許桂森
中文關鍵字 壓力  早期生活經驗  下視丘-腦下垂體-腎上腺軸 
英文關鍵字 stress  early life experience  HPA axis 
學科別分類
中文摘要 所謂的壓力,是指一個反應會去干擾身體的既有平衡。當人體感受到壓力時,會調控體內荷爾蒙分泌、中樞神經改變並與身體下視丘-腦下垂體-腎上腺軸 (HPA axis) 有高度相關性。但為何每個人對相同壓力時卻會有不一樣反應,其中的原因與機轉仍然不明。先前研究發現,早期生活經驗對於大腦發育扮演重要角色,後天生活經驗不同可能影響個體對於壓力有不一樣的感受性與適應性。因此本實驗主要探討目的:早期生活經驗是否會影響個體對壓力的感受性與適應性。我們實驗使用C57BL/6 mic,並分成”控制組”,”早期生活壓力暴露組”,” 豐富環境暴露組”三個組別進行實驗。實驗結果發現早期生活壓力暴露組別 [ELS, 限制減少cage 內巢片數量 (P2- P9)] 對於慢性社交挫敗壓力與急性壓力 都有較佳的調適能力。而豐富環境暴露組別 [EE, 豐富環境生長 (P1-P12)] 則與對照組無顯著差異。此外,我們也發現ELS組小鼠血液中皮質酮 (corticosterone) 濃度較對照組還高,並且在經歷30 分鐘束縛性壓力後血中皮質酮濃度ELS 組上升幅度較低,因此我們推測經歷ELS的小鼠其HPA axis 對壓力感受性較低。之後我們也去測量其在經歷過一個急性壓力刺激後的處理壓力能力的表現(強迫性游泳試驗、尾巴懸吊試驗),發現早期生活壓力暴露組也有較佳的調適能力。我們也去測量實驗小鼠在經歷一急性壓力刺激後的c-fos活性與葡萄醣皮質素、礦物質皮質素從細胞質轉移至細胞核的比例以確認小鼠對於壓力的反應,依然發現早期生活壓力暴露組對於壓力有較高的耐受性。在情緒方面,早期生活壓力暴露組並無顯著改變 (開放性空間試驗、十字迷宮試驗、糖水偏好性試驗)當我們把ELS小鼠利用手術將腎上腺移除 (adrenalectomy),其對於海馬迴 (hippocampus) CA1腦區之長期增益效應 (LTP) 與長期抑制效應 (LTD)的影響皆能被反轉。綜合以上結果,我們推論個體幼兒時期在高壓力環境下生活,會增加其對於壓力的耐受性,整體較為傾向錯位假說(Mismatch hypothesis)。此等結果也再次證明,早期生活經驗會影響個體大腦發育,對於壓力調控扮演重要角色。
英文摘要 Stress is a response that will disturb physiological homeostasis. Stimuli that disturbed originally physical homeostasis would modulate hormone secretion and had high correlation to hypothalamus-pituitary-adrenal axis (HPA axis). However, some individuals showed different resistance in same stress. Previous studies had reported that experiences showed a critical factor in stress response. Thus, the objective of this proposal is to evaluate the role of early life experiences in stress adaption and susceptibility. We found early life stress (ELS) mice model showed inoculation in chronic stress and acute stress, but enriched environment (EE) mice model did not. In addition, ELS mice model had higher basal level corticosterone and lower c-fos activity after stress stimulation. We also found ELS mice model glucocorticoid receptor and mineralocorticoid receptor rarely translocated from cytosol to nucleus after stress. Moreover, we also demonstrated the reason why ELS mice had stress resistance was high related to HPA axis. In coping behavior, ELS mice had high ability to modulate the second stress. These results suggest that ELS mice showed higher stress resistance that could be resulted from HPA axis alterations.
論文目次 目錄
中文摘要…………………………………………………………………I英文延伸摘要要………………………………………………………IV誌謝………………………………………………………………………VII目錄………………………………………………………………………..IX圖目錄……………………………………………………………………X縮寫檢索表……………………………………………………………XI 第一章 緒論………………………………………………………………1第二章 材料與方法………………………………………………………10
1.實驗動物…………………………………………………………………………11
2.早期生活經驗動物處理模式……………………………………………………11
3.海馬迴腦切片製備………………………………………………………………12
4.西方點墨法………………………………………………………………………14
5.免疫組織螢光染色……………………………………………………………18
6.腎上腺切除手術…………………………………………………………………20
7.小鼠壓力處理模式………………………………………………………………20
8.皮質固醇測定……………………………………………………………….…22
9.腎上腺皮質激素測定……………………………………………………………22
10.動物行為實驗……………………………………………………………………22
11.統計與分析………………………………………………………………………24
第三章 實驗結果……..…………………………………………………….25
第四章 討論………………………………………………………………35
第五章 圖表………………………………………………………………45
第六章 參考文獻…………………………………………………………59
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