飲食操弄對於小鼠記憶的影響

Abstract

卡路里節制(Calorie Restriction, CR)在許多不同物種上已被發現能有效降低與老化相關疾病發生的風險，以及增進認知功能的效果。然而，飲食成分中，哪一種營養成分扮演了主要的角色，藉由卡路里的節制調控了認知功能的可塑性。在本篇論文中，在不同營養成分下，本實驗利用物體辨認測驗(Novel Object Recognition, NOR)評估小鼠的記憶功能以及利用廣場測驗(Open Field Test)檢視小鼠自發性活動能力。發現飲食成分中的蛋白質(Protein)，其中的必需胺基酸-色胺酸(Tryptophan) 在卡路里節制的情況下扮演了主要的角色促使記憶的增強。本研究結果更進一步顯示: 卡路里節制能調控認知記憶功能，且需要藉由海馬迴(Hippocampus)裡的腺苷單磷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)活化的參與。另外，實驗結果發現AMPK的促進劑，Metformin，可以有效地增強小鼠的記憶表現；然而，AMPK的抑制劑，Compound C(CC)，能有效地反轉因卡路里節制而增強記憶的好處。綜合以上所有結果顯示: 本篇論文鑑定出小鼠在卡路里節制的情況下，飲食成分中的色胺酸，為最主要能調控並促進記憶增強的營養成分，且其過程必須透過海馬迴內AMPK的活化。該研究結果強烈顯示，其結果在臨床治療與老化相關的腦功能障礙上具有重要意義。

Calorie restriction (CR) has been shown to reduce the incidence of age-related diseases and improve cognitive functions in a variety of species. However, it remains unknown as to whether specific nutrient primarily works to mediate CR-induced cognitive plasticity. In this study, I evaluated the memory functions of mice under different dietary conditions by novel object recognition (NOR) tasks and the spontaneous motor activity by open field test. I found that protein derived essential amino acid-tryptophan played a major role in CR-induced memory enhancement. My results further revealed that hippocampal AMPK activation is essential for CR-mediated cognitive memory regulation since AMPK activation. I found that metformin, an AMPK activator, could significantly enhance the memory performance of mice, while CR-induced memory enhancement was attenuated by Compound C (CC), an AMPK inhibitor. Taken together, this study identified tryptophan as a critical nutrient that could mediate improved recognition memory essentially through AMPK activation under CR condition in mice. This study may have a critical implication in treating age-related brain dysfunctions in a clinical setting.