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系統識別號 U0026-0708201217451400
論文名稱(中文) 探討創傷性腦損傷後情緒障礙的細胞分子機制
論文名稱(英文) Investigation on the cellular and molecular mechanisms of mood disorders after traumatic brain injury
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 100
學期 2
出版年 101
研究生(中文) 鄭宜軒
研究生(英文) Yi-Hsuan Cheng
學號 s26994126
學位類別 碩士
語文別 英文
論文頁數 88頁
口試委員 指導教授-簡伯武
口試委員-司君一
口試委員-陳柏熹
中文關鍵字 創傷性腦損傷  憂鬱症 
英文關鍵字 traumatic brain injury  depression 
學科別分類
中文摘要 創傷性腦損傷是發展中國家常見的死因,也是造成小孩和青年後天損傷的主要原因。在臨床的研究中,憂鬱症好發於創傷性腦損傷的患者且為自殺的主要危險因子,但創傷性腦損傷所引發的憂鬱症其機轉至今仍不清楚。因此本實驗將探討創傷性腦損傷和憂鬱症之間的關聯。首先,透過行為試驗我們發現腦損傷大鼠的確出現憂鬱的傾向。接著,利用西方墨點法發現腦損傷會導致海馬迴組織中ERK及p38MAPK的磷酸化降低,但並不影響JNK。此外,給予選擇性血清素回收抑制劑─ fluoxetine (百憂解)後,發現能顯著改善腦傷老鼠的憂鬱,且反轉ERK與p38MAPK磷酸化降低的情形。然而, fluoxetine造成腦傷老鼠靜止不動的時間減少及反轉ERK磷酸化降低的情況會被選擇性血清素生合成抑制劑─ para-chlorophenylalanine (PCPA)消除,但p38MAPK的磷酸化卻不受影響。此外,透過強迫性游泳實驗觀察,發現在給予fluoxetine前先給予ERK的抑制劑─SL327會移除fluoxetine的抗憂鬱效果。從以上實驗結果可知,ERK在創傷性腦損傷誘發的憂鬱中可能扮演了重要的角色。
英文摘要 Traumatic brain injury (TBI) is the most common cause of death and acquired disability among children and young adults in developed countries. In clinical studies, there are higher incidence of depression, anxiety and memory impairment after TBI. Furthermore, depression is a major risk factor for suicide and the mechanisms behind the TBI-induced depression remain unclear. The purpose of this study is to investigate the relationship between TBI and depression. After 4 days of TBI, we found that TBI might result in the etiology of some forms of depression through behavioral tests. At the same time, the western blotting analysis revealed that phosphorylated levels of extracellular signal regulated kinases (ERK) and p38mitogen-activated protein kinase (p38MAPK) were decreased in hippocampus of TBI rats whereas Jun N-terminal kinases (JNK) was unaltered. Chronic administration of fluoxetine, an antidepressant of the selective serotonin reuptake inhibitor, significantly improved the depression in TBI rats and reversed phosphorylated levels of ERK and p38 MAPK to control level. Furthermore, pretreatment of para-chlorophenylalanine (PCPA), an inhibitor of serotonin biosynthesis, blocked fluoxetine-induced reduction in immobility during forced swim test (FST), and abolished the effect of fluoxetine on ERK but not on p38MAPK. In addition, through FST, we found that inhibition of ERK removed antidepressant effect of fluoxetine by SL327.Together these results suggest that ERK may have roles in TBI-induced depression.
論文目次 中文摘要 Abstract in Chinese 1
英文摘要 Abstract in English 3
Acknowledgement 5
Content 6
圖表索引 Lists of Figures and Tables 7
縮寫檢索表 Abbreviations 10
Chapter1: Introduction 12
Chapter2: Specific Aims 33
Chapter3: Materials and Methods 35
Chapter4: Results 45
Chapter5: Discussion 54
References 61
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