- 學位論文
探討芳樟醇對MPP+/MPTP誘導帕金森氏症實驗模式之保護作用
The protective effects of linalool on MPP+/MPTP-induced experimental models of Parkinson’s disease
摘要
帕金森氏症是常見的中樞神經退化性疾病之一，其致病機轉為中腦黑質的多巴胺神經退化，造成大腦紋狀體的多巴胺不足，最終導致運動及非運動症狀。帕金森氏症的病因及分子機轉極為複雜，目前研究顯示氧化壓力及細胞凋亡是造成多巴胺神經損傷的重要原因。芳樟醇是許多芳香植物的主要成分，許多研究指出它具有抗氧化、抗發炎、抗憂鬱及抗焦慮等作用。本論文之研究目的將探討芳樟醇對於多巴胺神經細胞的保護作用，以及觀察它對於帕金森氏症小鼠之運動、憂鬱及焦慮的改善作用。本研究以MPP＋誘發多巴胺SH-SY5Y細胞及大鼠初代胚胎神經細胞產生氧化性損傷，並以MPTP誘導小鼠產生類帕金森氏症狀。研究結果顯示，對於MPP＋處理的神經細胞，芳樟醇能降低其氧化壓力及細胞凋亡相關蛋白表現，增加神經滋養因子表現，減少神經軸突短縮及增加細胞存活率。此外，在帕金森氏症小鼠模式中，芳樟醇不僅減少中腦黑質的多巴胺神經損失，也明顯促進小鼠運動功能並改善其憂鬱及焦慮症狀。基於上述發現，我們證實芳樟醇具有多巴胺神經細胞的保護作用及改善帕金森氏症的運動及非運動症狀之潛在益處。
並列摘要
Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases which caused by progressive degeneration of dopaminergic neurons in the substantia nigra and depletion of dopamine in the striatum, eventually leading to motor and non-motor symptoms. The pathogenesis and molecular mechanism of PD is extremely complicated. Current studies show that oxidative stress and apoptosis are important causes of dopaminergic neuronal damage. Linalool is a common ingredient in aromatic plants, and many studies have indicated that it has antioxidant, anti-inflammatory, anti-depressant and anti-anxiety effects. The aim of this thesis was to investigate the protective effects of linalool on dopaminergic neurons and its effects on motor function, depression and anxiety in PD-like mice. In this study, MPP+ was used to induce oxidative damage in dopaminergic SH-SY5Y cells and rat primary embryonic neurons, and MPTP was used to induce Parkinson's-like symptoms in mice. For MPP+ treated neurons, linalool downregulated oxidative stress- and apoptosis-related proteins, upregulated neurotrophic factor expression, reduced neurite retraction and increased cell viability. Moreover, in PD-like mice, linalool not only attenuated the loss of dopamine neurons in substantia nigra but it also improved the motor activity and the symptoms of depression and anxiety of mice. Based on the above findings, we demonstrate that linalool has the protective effects on dopaminergic neurons and has the potential benefits for improving the motor and non-motor symptoms of Parkinson's disease.