Effects of calorie restriction on learning and memory

• Main Authors: Hwang, Nai Hsuan, 黃乃軒
• Other Authors: Liao, Ruey Ming
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/85858440568012395150

碩士 === 國立政治大學 === 神經科學研究所 === 101 === 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.