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| Title: | 卡路里節制對於學習與記憶的影響
Effects of calorie restriction on learning and memory |
| Authors: | 黃乃軒
Hwang, Nai Hsuan |
| Contributors: | 廖瑞銘
王培育
Liao, Ruey Ming
Wang, Pei Yu
黃乃軒
Hwang, Nai Hsuan |
| Keywords: | 卡路里節制
學習
記憶
血清素
Calorie restriction
learning
memory
serotonin |
| Date: | 2012 |
| Issue Date: | 2013-07-23 13:21:27 (UTC+8) |
| Abstract: | 很多人在自然老化的過程中往往都會經歷認知功能的衰退。而這樣的結果也導致人們無法正常的學習新知識、儲存或是提取記憶。卡路里節制(Calorie Restriction, CR)除了可以增進身體健康外，在過去的研究中也發現在許多生物物種上也看到有延長壽命的效果。相反的，高脂肪(High Fat, HF)的飲食則是增加了罹患老化相關疾病的風險。本篇論文利用短期的卡路里節制(相較於正常飲食攝取的60%)和高脂肪飲食操弄來檢驗其對於年輕公鼠(10週大)學習與記憶能力的影響。在連續6到10週的飲食操弄後，正常飲食、 卡路里節制和高脂肪組別體重的變化分別為20.7%、-19.9%和28.4％。利用高空T型迷宮(Elevated T Maze, ETM)、被動規避儀(Passive Avoidance, PA)、物體辨認測驗(Novel Object Recognition, NOR)和水迷津(Morris Water Maze, MWM)等四種認知行為作業中，我發現卡路里節制顯著的增進小鼠學習與記憶能力的表現，而高脂肪飲食則是沒有顯著的影響。而在廣場測驗(Open Field Test)中，我發現三種飲食操弄組別皆不影響小鼠的行動能力，顯示卡路里節制增進學習與記憶的效果並非因為受到行動能力的干擾所導致。
我發現利用選擇性血清素回收抑制劑(Selective Serotonin Reuptake Inhibitor, SSRI) fluoxetine和血清素亞型6受體促進劑(5-HT6R Agonsit) WAY208466可以阻斷卡路里節制增進學習記憶表現的效果，顯示卡路里節制增進認知功能的效果很有可能是透過作用在5-HT6血清素亞型受體相關機制所產生。 除此之外，卡路里節制顯著降低了平時5-HT6/PKA(Protein Kinase A, PKA)訊號表現量，然而卻可增強5-HT6血清素亞型受體促進劑誘發PKA磷酸化表現的效能。而在長期給予磷酸二酯酶-4(Phosphodiesterase-4, PDE4)抑制劑rolirpam的情況下，我發現透過增加環狀一燐酸腺(Cyclic Adenosine Monophosphate, cAMP)強化PKA的活性同樣也可以阻斷卡路里節制增進學習記憶的效果。綜合這些實驗結果，我們推測卡路里節制透過調控5-HT6/PKA相關機制導致最後增進學習與記憶的效果。
One common phenomenon during the natural process of aging is that most people experience a progressive decline in overall cognitive functions. This causes people to lose their ability to learn new information and store or retrieve from memory. Calorie restriction (CR) has been shown to improve health and extend lifespan in a variety of species, whereas high-fat diet may increase the risk of age-related diseases. In this study, we examine the effects of short-term CR (60% of the normal calorie intake) and high-fat (HF) diet on learning and memory in young male mice (10-week-old). After 6 to 10 weeks under normal, CR, and HF diet, animals showed 20.7%, -19.9% and 28.4% in body weight change respectively. Using elevated t maze (ETM), passive avoidance (PA), novel object recognition (NOR) and morris water maze (MWM) task, we found that CR regimen significantly improved learning and memory ability in mice while HF had no effect. In open field test, all diet regimens had no effect on motor functions, suggesting that diet-induced behavioral changes were not due to alterations in general motor activities of mice.
The procognitive effects of CR were likely to act through a serotonin 6 receptor (5-HT6)-related pathway since fluoxetine, a selective serotonin reuptake inhibitor, and 5-HT6 agonsit (WAY208466 dihydrochloride) could reverse the effects of CR on learning and memory. Furthermore, CR significantly reduced basal 5-HT6/PKA signaling but enhanced the efficacy of 5-HT6 agonist induced PKA phosphorylation. Chronic treatment with rolipram, which enhances PKA activity through increasing cAMP levels, could compromise the actions of CR. In summary, our data suggested that CR might enchance cognitive function through modulating the 5-HT6/PKA related pathway. |
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| Description: | 碩士
國立政治大學
神經科學研究所
100754001
101 |
| Source URI: | http://thesis.lib.nccu.edu.tw/record/#G0100754001 |
| Data Type: | thesis |
| Appears in Collections: | [神經科學研究所] 學位論文
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