甲基安非他命所引發的黑質紋狀體多巴胺神經毒性已知可受到蛋白質合成抑制劑所阻斷。這顯示了蛋白質的合成在甲基安非他命毒性的產生上扮演著關鍵性的角色。本研究的目的在於尋找這些涉及甲基安非他命神經毒性的蛋白質（特別是神經毒性蛋白）。在本研究中我們利用二維蛋白質電泳以及質譜儀的技術分離並鑑定出特定的蛋白質。實驗組是連續注射三劑甲基安非他命的小鼠，每劑的劑量是每公斤十毫克；控制組則是注射生理食鹽水的小鼠。所用以進行前述實驗步驟的組織為小鼠腦部的兩側紋狀體。經過電腦軟體以及統計分析之後我們發現，於實驗組當中有五個蛋白質的強度表現較控制組為強，另外有十五個蛋白質的強度表現則較控制組為弱，我們經由質譜儀鑑定出其中十一個蛋白質的身分。從上述實驗中，我們得以確認出與甲基安非他命所引發多巴胺神經毒性相關的蛋白質。接下去的研究重點將放在進一步去確立這些蛋白質在毒性機制中所扮演的角色。

　　Methamphetamine (MA)-induced nigrostriatal dopamine neurotoxicity can be reversed by protein synthesis inhibitor treatment, indicating the pivotal role of protein synthesis in this MA-induced dopaminergic neurotoxicity paradigm. This study aims to identify the specific neurotoxic proteins responsible for such nigrostriatal dopaminergic toxicity. Employing the two-dimensional gel electrophoresis (2-DE) technique, followed by mass spectrometry (MS), I obtained those proteins involved in such toxicity by contrasting the protein expression profiles of striatal samples dissected from MA-treated against them from saline-treated mice. To avoid necrotic and apoptotic confounds, striata were dissected out thirty minutes after the third dose of MA (10mg/kg for each dose) or saline administration. Approximately 300 spots were visualized by silver stain and analyzed on an ImagerMaster Labscan software for the quantitation of protein expression. Comparing the striatal protein expression profiles, five protein spots exhibited a significant increase in intensities and fifteen spots revealed a decrease in intensities in MA-treated group. Subsequent MS analysis results revealed and identified eleven among above protein spots with altered levels. By using this approach we are capable of identifying the candidates of neurotoxic and neuroprotective proteins involved in the MA-induced nigrostriatal dopamine neurotoxicity.

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