臺灣大學: 食品科技研究所孫璐西邱博恩Chiu, Po-EnPo-EnChiu2013-03-212018-06-292013-03-212018-06-292011http://ntur.lib.ntu.edu.tw//handle/246246/248407阿滋海默症(Alzheimer’s disease)是失智症所有類型中最廣泛發生的一型，是一種會導致認知能力下降以及情緒與行為產生改變的神經退化性疾病。阿滋海默症的主要病理特徵主要包含細胞外的類澱粉胜肽沉積以及細胞內的Tau蛋白過磷酸化產生神經糾結而進一步造成記憶喪失。老化促進小鼠(Senescence-accelerated mouse prone-8, SAMP8)模式是一種以年齡為發展基礎而非基因轉殖的動物模式。就阿滋海默症的類型而言，SAMP8小鼠更加貼近以年齡為危險因子的晚發型阿滋海默症。此外，SAMP8小鼠也會隨著老化產生認知能力下降以及類澱粉胜肽的沉積。因此，本研究的目的為藉由在飲食中添加芝麻酚或槀本內酯以探討其對於SAMP8小鼠是否具有延緩學習與記憶能力損傷以及降低阿滋海默症病理特徵之潛力。本研究藉由餵食老化促進小鼠十二週芝麻酚與槀本內酯，並發現其對於鞏固SAMP8小鼠之恐懼記憶有顯著的效果，並且也能夠促進空間的學習記憶能力。進一步使用酵素連結免疫分析法，餵食槀本內酯與芝麻酚具有使類澱粉胜肽下降的趨勢，而在組織免疫染色中也可以看到類似的結果。以肝臟過氧化產物分析SAMP8小鼠的氧化壓力，也發現餵食槀本內酯與芝麻酚有下降氧化壓力的趨勢。進行認知行為時間結果、類澱粉胜肽含量、氧化壓力進行交叉比較，可進一步發現認知行為的損傷與類澱粉胜肽並沒有顯著的高度相關性；氧化壓力與類澱粉胜肽也無顯著相關性。由本研究可推測類澱粉胜肽與氧化壓力在SAMP8小鼠模式中，並非是造成認知能力損傷的主要原因。Alzheimer’s disease is the most common form of dementia. It is a neurodegenerative disorder characterized by impairment in cognitive functions and changing in mood and behavior. The hallmarks of this disease are the presence of extracellular beta-amyloid deposition and intracellular hyperphosphorylated tau protein. Senescence-accelerated mouse prone-8 (SAMP8) is an age-accelerated mice model rather than gene-mutated mice model. In addition, SAMP8 mice also show the cognitive impairment and beta amyloid deposition. The objectives of this study were to investigate the potentials of sesamol and Z-ligustilide to ameliorate learning / memory impairment and Alzheimer’s disease pathophysiology in SAMP8 mice. Our results demonstrated that a 12-week oral administration of Z-ligustilide or sesamol could consolidate the fear-conditioning memory of SAMP8 mice and also slightly improved the spatial learning and memory. Using immunohistochemical (IHC) staining for certain brain sections of mice, we found that there was a decreasing trend in the deposition of beta amyloid after administration of sesamol and Z-ligustilide. Using ELISA to detect beta amyloid, the results were similar to IHC staining; however the treatment groups were not significantly different from the control group. To evaluate the oxidative stress status of the mice, liver TBARS were determined. We found that treatment groups had lower TBARS level. To correlate the results of behavior tests, beta amyloid content, and oxidative stress status, we concluded that there was neither strong correlation between cognitive impairment and beta amyloid, nor oxidative stress and beta amyloid. These results suggested that beta amyloid and oxidative stress may not be the crucial factors to influence cognitive ability in SAMP8 mice.11712783 bytesapplication/pdfen-US阿滋海默症老化促進小鼠SAMP8小鼠學習記憶能力損傷薑黃素?本內酯芝麻酚莫氏水迷津被動迴避試驗senescence-accelerated mouse prone-8 (SAMP8) micelearning and memory impairmentcurcuminZ-ligustilidesesamolMorris water mazeinhibitory avoidance taskthesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/248407/1/ntu-100-R98641011-1.pdf