title: Influence of age-related learning and memory capacity of mice: different effects of a high and low caloric diet.
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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.affiliation: 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. rong_wang72@aliyun.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Ma
authors.affiliation: Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, #2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Bao-Lei
authors.initials: BL
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Jing-Shuang
authors.initials: JS
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000502:physiology; D031204:Caloric Restriction / Q000379:methods; D004032:Diet; D002149:Energy Intake; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019636:Neurodegenerative Diseases / Q000503:physiopathology / Q000517:prevention & control; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: Astrocyte; Autophagy; Caloric restriction; High-calorie diet