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年龄对小鼠学习和记忆能力的影响:高、低热量饮食的不同作用

Influence of age-related learning and memory capacity of mice: different effects of a high and low caloric diet.

作者信息

Dong Wen, Wang Rong, Ma Li-Na, Xu Bao-Lei, Zhang Jing-Shuang, Zhao Zhi-Wei, Wang Yu-Lan, Zhang Xu

机构信息

Central Laboratory, Xuan Wu Hospital, Capital Medical University, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, #45 Changchun Street, Xicheng District, Beijing, 100053, China.

Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, #2 Anzhen Road, Chaoyang District, Beijing, 100029, China.

出版信息

Aging Clin Exp Res. 2016 Apr;28(2):303-11. doi: 10.1007/s40520-015-0398-0. Epub 2015 Jul 3.

Abstract

BACKGROUND

Recent studies indicate that consumption of the different calorie diet may be an important way to accelerate or slow the neurodegenerative disorder related to age. Long-term consumption of a high-calorie diet affects the brain and increase the risk of neurodegenerative disorders. And consumption of a low-calorie diet (caloric restriction, CR) could delay aging, and protect the central nervous system from neurodegenerative disorders. The underlying mechanisms have not yet been clearly defined.

METHOD

Thirty 6-week-old C57/BL6 mice were randomly assigned to a NC group (fed standard diet, n = 10), a CR group (fed a low-calorie diet, n = 10) or a HC group (fed a high-calorie diet, n = 10) for 10 months. Body weight was measured monthly. Learning and memory capacity were determined by Morris water maze. Pathological changes of the hippocampus cells were detected with HE and Nissl staining. The expression of GFAP was determined by immunofluorescence and western blot. The expression of mTOR, S6K and LC3B in the hippocampus was determined by immunofluorescence.

RESULTS

After feeding for 10 months, compared with mice in the NC group, mean body weight was significantly higher in the HC group and significantly lower in the CR group. The result of Morris water maze showed that compared with mice in the NC group, the learning and memory capacity was significantly increased in the CR group, and significantly decreased in the HC group. HE and Nissl staining of the hippocampus showed cells damaged obviously in the HC group. In the hippocampus, the expression of GFAP, mTOR and S6K was increased in the HC group, and decreased in the CR group. The expression of LC3B was decreased in the HC group, and increased in the CR group.

CONCLUSIONS

Long-term consumption of a high-calorie diet could inhibit autophagy function, and facilitate neuronal loss in the hippocampus, which in turn aggravate age-related cognition impairment. And consumption of a low-calorie diet (caloric restriction, CR) could enhance the degree of autophagy, protect neurons effectively against aging and damage, and keep learning and memory capacity better.

摘要

背景

近期研究表明,摄入不同热量的饮食可能是加速或减缓与年龄相关的神经退行性疾病的重要方式。长期食用高热量饮食会影响大脑并增加神经退行性疾病的风险。而食用低热量饮食(热量限制,CR)可以延缓衰老,并保护中枢神经系统免受神经退行性疾病的侵害。其潜在机制尚未明确。

方法

将30只6周龄的C57/BL6小鼠随机分为正常对照组(喂食标准饮食,n = 10)、热量限制组(喂食低热量饮食,n = 10)或高热量组(喂食高热量饮食,n = 10),持续10个月。每月测量体重。通过莫里斯水迷宫测定学习和记忆能力。用苏木精-伊红(HE)和尼氏染色检测海马细胞的病理变化。通过免疫荧光和蛋白质印迹法测定胶质纤维酸性蛋白(GFAP)的表达。通过免疫荧光法测定海马中雷帕霉素靶蛋白(mTOR)、核糖体蛋白S6激酶(S6K)和微管相关蛋白1轻链3(LC3B)的表达。

结果

喂食10个月后,与正常对照组小鼠相比,高热量组小鼠的平均体重显著更高,热量限制组小鼠的平均体重显著更低。莫里斯水迷宫实验结果显示,与正常对照组小鼠相比,热量限制组小鼠的学习和记忆能力显著增强,高热量组小鼠的学习和记忆能力显著下降。海马的HE和尼氏染色显示,高热量组细胞损伤明显。在海马中,高热量组GFAP、mTOR和S6K的表达增加,热量限制组表达降低。高热量组LC3B的表达降低,热量限制组表达增加。

结论

长期食用高热量饮食可抑制自噬功能,促进海马神经元丢失,进而加重与年龄相关的认知障碍。而食用低热量饮食(热量限制,CR)可增强自噬程度,有效保护神经元免受衰老和损伤,并保持较好的学习和记忆能力。

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