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研究生:沈哲緯
研究生(外文):Jhe-Wei Shen
論文名稱:Alpha1HT型鈣離子通道基因剔除小鼠之依賴海馬迴學習
論文名稱(外文):Hippocampal-dependent learning of micedeficient in α1H T-type calcium channel
指導教授:劉怡均劉怡均引用關係
指導教授(外文):Ingrid Y.-C. Liu
學位類別:碩士
校院名稱:慈濟大學
系所名稱:人類遺傳研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
畢業學年度:95
語文別:中文
論文頁數:59
中文關鍵詞:Alpha1H T 型鈣離子通道
外文關鍵詞:α1H T-type calcium channel
相關次數:
  • 被引用被引用:1
  • 點閱點閱:351
  • 評分評分:
  • 下載下載:2
  • 收藏至我的研究室書目清單書目收藏:0
鈣離子通道的開啟,會引發許多細胞內生物化學的反應,例
如肌肉的收縮、基因表達、賀爾蒙與神經傳導素的分泌等等。其
中鈣離子通道家族裡的α1H T 型鈣離子通道,在海馬迴腦區中高
度表達,而目前研究指出,海馬迴又跟情境學習與空間記憶有所
關聯,所以α1H T 型鈣離子通道在學習與記憶上,應扮演著著某
種程度的重要性。
為了探討研究α1H T 型鈣離子通道與學習記憶的關連性,我
們將異型接合基因剔除小鼠(heterozygous knockout mice)、同
型接合基因剔除小鼠(homozygous knockout mice)與野生型的小
鼠(wild-type mice),進行依賴海馬迴訓練的學習測驗,包含痕
跡恐懼制約實驗(Trace fear conditioning test)、被動躲避學
習試驗(Step-through and Step-down passive avoidance test)
等。目前初步的結果顯示α1H 基因剔除的小鼠在經過上述的行為
測試後,的確有出現學習不良的現象。
為了更進一步確定α1H T 型鈣離子通道是否是由腦部直接影
響而造成依賴海馬迴相關學習的缺陷,於是使用T 型鈣離子通道
抑制劑mibefradil 與ethosuximide 對腦部進行局部性功能抑制
的實驗,結果顯示使用抑制劑的組別也一樣造成學習障礙的現
象,證實α1H T 型鈣離子通道確實在依賴海馬迴學習試驗上扮演
一個重要的角色。
Voltage-dependent calcium channels trigger many intracellular
biochemical events, including muscle contraction, gene expression and
secretion of hormones and neurotransmitters. Of all the voltage-gated
calcium channels, the 1H T-type Ca2+ channel (Cav3.2) is highly
expressed in the hippocampus, where is correlated with contextual
learning and spatial memory. Therefore, we hypothesize that Cav3.2
plays a critical role in hippocampal-dependent learning. In order to
investigate the functional role of the 1H channel in learning and
memory, we performed hippocampal-dependent behavior tests
including trace fear conditioning and passive avoidance task on 1H
homozygous knock-out mice, 1H heterozygous knockout mice and
wild type mice. Results showed that 1H-/- mice are impaired in
contextual fear learning, step-down and step-through tasks.
Subsequently, we infused T type Ca2+ channel blockers (mibefradil
and ethosuximide) to locally knock down the function of 1H T-type
Ca2+ channel. Results showed that mice received blockers displaying
deficits in contextual fear learning. The data indicate that 1H
influences hippocampal-dependent learning via the central nervous
system directly.
致謝 ………………………………………Ⅰ
英文摘要 ………………………………………Ⅱ
中文摘要 ………………………………………Ⅲ
縮寫全名對照表 ………………………………………Ⅳ
目錄 ………………………………………Ⅴ
緒論 ………………………………………1
材料與方法 ………………………………………10
結果 ………………………………………20
討論 ………………………………………24
圖表 ………………………………………29
參考文獻 ………………………………………51
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