純物質AG對阿茲海默症基因轉殖模式小鼠之影響

Abstract

截至2015年，全世界已累計約4,800萬人罹患阿茲海默症，其為最常見之神經退化性疾病之一。然而，此疾病目前仍無法治癒，因此相關藥物的發展刻不容緩。實驗室先前建立的篩藥平台已篩選約莫12種中草藥單方，其中部分單方具有降低神經細胞去極化的潛力。研究也探索了其中一種，我們暫時將其命名為AG的純物質，在神經細胞上的作用機制。本研究即延伸AG在AD疾病模式鼠中可能的作用。小鼠分為四組：正常對應AD模式鼠以及是否給予AG，我們在小鼠皮下注射AG一個月後，肝、腎組織切片之H&E染色顯示注射溶劑之控制組與實驗組之間並無明顯改變。以阿茲海默模式小鼠 (簡稱J20小鼠) 進行行為實驗，研究發現，在開放空間測試與Y形迷宮的研究中，AG尚無逆轉J20小鼠活動亢進、短期記憶下降的作用。進一步以莫氏水迷津探討後卻發現，AG雖無法防止此種模式鼠記憶的下降，卻顯著強化了野生型小鼠之長期、短期記憶力。綜合上述，以目前給藥時程設計，尚無法確定AG對於改善記憶喪失是否有效，但對於正常小鼠之記憶行為可能有所助益，從這面向來看，AG仍具有發展成增進記憶之健康食品之潛力。

There were approximately 48 million people developing Alzheimer’s disease (AD), one of the mostcommon neurodegenerative diseases. Nevertheless, there is no cure for this disease so that the related drug development becomes warranted. We have previously found 6 out of 12 Chinese herbal medicines (CHMs) have the potential to ameliorate abnormally neuronal depolarization by using our drug screening platform. One of the pure compounds, temporarily named AG, has also been investigated its cellular mechanism on the primary neurons. Therefore, the efficacy of AG on AD mice model, J20, is further investigated. Mice were divided into four groups, wild type or J20 were injected with or without AG. AG were injected into mice subcutaneously for a month. The H&E staining of liver and kidney tissues showed no significant change compared to the ones injected by vehicle. AG doesn’t recover the hyperactivity and temporary memory in J20 mice assayed by using open field test and Y-maze analysis. AG can’t alleviate the memory loss in the mouse model analyzed by utilizing Morris water maze. However, AG can enhance the short-term and long-term memory on wild-type mice. Taken together, current format/timing of giving AG to mice shows inconclusive effect on memory deterioration of J20 mice. It has the benefit on enhancing memory of normal mice. Hence, it could still has the potential to develop into a dietary supplement on enhancing memory.