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研究生:羅凱仁
研究生(外文):Kai-Ren Luo
論文名稱:兩種憂鬱症大鼠動物模式之血清及區域腦組織腦源神經滋養因子和S100B的濃度變化
論文名稱(外文):Serum and Regional Brain BDNF and S100B Level Changes in Two Depression Animal Models of Rats
指導教授:黃銀河黃銀河引用關係黃銀河黃銀河引用關係
指導教授(外文):Yn-Ho HuangYn-Ho Huang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:解剖暨細胞生物學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:78
中文關鍵詞:憂鬱症腦源神經滋養因子嗅球摘除慢性不可預測壓力
外文關鍵詞:depressionbrain-derived neurotrophic factor(BDNF)olfactory bulbectory (OBX)chronic unpredictable stress (CUS)
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背景: 憂鬱症是一種複合症狀的心理疾病。目前憂鬱症的致病成因仍不清楚,然而一些臨床研究發現,憂鬱症病人的血清顯示有較高的S100B濃度以及有較低的腦源神經滋養因子(BDNF)的濃度。這項研究主要探討這兩種分子在不同憂鬱症動物模式上周圍與中樞神經的改變。方法: 雄性SD大鼠隨機分組為(1) 嗅球摘除組(2) sham組(嗅球摘除組之對照組) (3) 慢性不可預測壓力組(4) 正常控制組(慢性不可預測壓力組之對照組)。手術後兩周sham及嗅球摘除組進行開放空間測試。持續壓力三周或不作任何處理三周,不可預測壓力組及正常控制組進行開放空間測試,蔗糖偏好測試及強迫游泳測試。行為測試後一天,所有大鼠進行心臟採血以獲取血清。之後大腦被立即從頭骨取出並解剖為前額葉皮質區,紋狀體及海馬迴。結果:與其對照組比較,開放空間測試顯示嗅球摘除組有較高的活動力及不可預測壓力組仍保持正常的活動力。此外,與其對照組比較,不可預測壓力組表現出對蔗糖溶液較低的興趣以及在強迫游泳測試有較長時間靜止不動。與其對照組比較,血清中S100B濃度在嗅球摘除組及不可預測壓力組有較高的濃度,然而後者卻在前額葉皮質區有較低的濃度。相同地,我們發現血清中BDNF在嗅球摘除組有較高的濃度,而在不可預測壓力組則是在海馬迴有較高的濃度。無論任何一組在血清與區域腦組織間S100B濃度變化都沒有顯著相關性,然而BDNF在正常控制組與sham組則顯示血清與腦前額皮質呈現顯著的負相關性。推論:在血清中的S100B變化量可能無法直接反應前額葉皮質區,紋狀體及海馬迴的S100B變化,而血清與腦前額皮質BDNF可能存在負相關性。血清中的S100B濃度變化在憂鬱症動物模式與臨床發現相似,但血清或海馬迴BDNF濃度變化在憂鬱症動物模式卻與臨床發現相反。這些結果顯示SD大鼠適合作為探討憂鬱症病人的血清S100B濃度改變之憂鬱症動物模式。
Backgrounds: Major depression is a mental disorder that includes many symptoms. In present, the pathology of depression is not clear, however, some clinical studies have found that there are higher level on S100B and lower level on brain-derived neurotrophic factor (BDNF) in the serum of patients with depression. The aim of the study is to investigate the changes of the two proteins, BDNF and S100B, in serum and specific brain area in two animal models of depression. Methods: Male Sprague–Dawley (SD) rats were divided into: (1) olfactory bulbectory (OBX) group (n=12); (2) sham group (control group for OBX group) (n=12); (3) chronic unpredictable stress (CUS) group (n=12); (4) normal group (control group for CUS group) (n=12). Two weeks after surgery, sham and OBX groups received open field test. Three weeks after persistent unpredictable stress or no stress in the home cage, CUS and normal groups received open field test, sucrose preference test and forced swimming test (FST). Next day after behavioral tests, all rats were scarified for blood collection by intracardiac puncture and, after that, brains were removed off and dissected into prefrontal cortex, striatum and hippocampus. S100B and BDNF levels were measured by ELISA for serum, prefrontal cortex, striatum and hippocampus. Results: Open field test showed that there was higher activity on OBX group compared with sham group. Besides, CUS group expressed lower interesting to sucrose solution and longer time immobility in FST compared with its control group. Significant increase in serum S100B level was found in OBX and CUS groups compared with their control groups, however, S100B decreased in prefrontal cortex in CUS group. Similarly, BDNF significantly increased in serum of OBX group and in the hippocampus of CUS group compared with their control groups. No significant correlation between serum and regional brain S100B was found in any group, but significant negative correlation between serum and prefrontal cortex BDNF was noted in normal and sham groups. Conclusion: S100B level change in serum could not directly reflect its changes in three regional brains (prefrontal cortex, striatum and hippocampus), however, there may exist a negative correlation between serum and regional BDNF levels. Depression animal models showed similar changes in serum S100B levels as the findings in depressed patients, however, contrast findings were found in the serum or hippocampal BDNF levels between depression animal models and previous clinical findings. Our findings suggest that rats could be used as a good model to study S100B changes in depressed patients.
論文審定同意書..........................................Ⅰ
論文電子檔審定證明書....................................Ⅱ
誌謝...................................................III
目 錄...................................................V
Abstract................................................VI
中文摘要..............................................VIII
緒言.....................................................1
一. 憂鬱症...............................................1
二. 腦部衍生蛋白質.......................................1
三. 憂鬱症動物模式.......................................4
四. 似憂鬱症行為.........................................6
五. 憂鬱症相關的腦區.....................................7
研究目的.................................................9
材料與方法..............................................10
一. 實驗動物............................................10
二. 嗅球摘除手術........................................10
三. 慢性不可預測壓力....................................11
四. 行為測試............................................12
五. 犧牲與樣本處理......................................15
六. 蛋白質分析..........................................15
七. S100B ELISA.........................................16
八. BDNF ELISA..........................................17
九. 統計分析............................................18
結果....................................................19
一. 似憂鬱症大鼠的體重變化..............................19
二. 似憂鬱症大鼠的活動力變化............................20
三. 慢性不可預期壓力大鼠的蔗糖偏好性降低................21
四. 慢性不可預期壓力大鼠強迫游泳測試不掙扎的時間增加....21
五. 似憂鬱症大鼠血清與區域腦組織S100B 表現量的差異......22
六. 似憂鬱症大鼠血清與區域腦組織BDNF表現量的差異........24
七. 血清與腦區域的相關性................................26
討論....................................................28
結論....................................................35
圖表....................................................36
參考文獻................................................66
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