飲食操弄對於小鼠記憶的影響

Effects of nutritional manipulations on memory in mice

鄭雅云(Ya-Yun Cheng)

指導教授 ： 王培育

國立臺灣大學/醫學院/腦與心智科學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.10715

摘要

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。

關鍵字

卡路里節制 ； 再認記憶 ； 蛋白質 ； 色胺酸 ； AMPK ； 物體辨認測驗

並列摘要

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.

並列關鍵字

calorie restriction ； protein ； tryptophan ； AMPK ； memory ； NOR

參考文獻

Anton, S., Leeuwenburgh, C. (2013). Fasting or caloric restriction for healthy aging. Exp Gerontol, 48(10), 1003-1005. doi: 10.1016/j.exger.2013.04.011

Antosh, M., Whitaker, R., Kroll, A., Hosier, S., Chang, C., Bauer, J., . . . Helfand, S. L. (2011). Comparative transcriptional pathway bioinformatic analysis of dietary restriction, Sir2, p53 and resveratrol life span extension in Drosophila. Cell Cycle, 10(6), 904-911.

Arias, N., Mendez, M., Arias, J. (2015). The recognition of a novel-object in a novel context leads to hippocampal and parahippocampal c-Fos involvement. Behav Brain Res, 292, 44-49. doi: 10.1016/j.bbr.2015.06.012

Ayala, V., Naudi, A., Sanz, A., Caro, P., Portero-Otin, M., Barja, G., Pamplona, R. (2007). Dietary protein restriction decreases oxidative protein damage, peroxidizability index, and mitochondrial complex I content in rat liver. J Gerontol A Biol Sci Med Sci, 62(4), 352-360.

Broadbent, N. J., Squire, L. R., Clark, R. E. (2004). Spatial memory, recognition memory, and the hippocampus. Proc Natl Acad Sci U S A, 101(40), 14515-14520. doi: 10.1073/pnas.0406344101