title: Comparison of the effects of resveratrol and caloric restriction on learning and memory in juvenile C57BL/6J mice.
abstract: OBJECTIVE
  Both caloric restriction (CR) and resveratrol (RSV) have been shown to improve learning and memory, but their potential effects in juvenile animals were unknown. Here, we evaluated the effects of RSV and CR on learning and memory function in juvenile mice and investigated potential molecular mechanisms.
  
  
  METHODS
  Six-week-old C57BL/6J mice were assigned to one of three different dietary groups: normal control (stock diet) (n=12), CR diet (30% caloric reduction diet) (n=12), and RSV diet (stock diet supplemented with 18.6 mg/kg RSV) (n=12), for 6 months. Body weight and blood glucose were measured every 4 weeks. Serum cholesterol and serum triglyceride levels were examined using biochemical methods. Serum insulin and insulin-like growth factor 1 (IGF-1) levels were evaluated using enzyme linked immunosorbant assay (ELISA), and protein expression of silent mating type information regulation 2 homology 1 (SIRT1), p53, p16, peroxisome proliferator-activated receptor γ (PPARγ), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), phosphorylated-cAMP response element-binding protein (p-CREB), and IGF-1 were examined with immunohistochemistry.
  
  
  RESULTS
  Although long-term CR diet did not alter physiological conditions in juvenile mice relative to control, RSV supplementation slightly elevated blood glucose, serum triglyceride, and serum insulin levels. Both CR and RSV improved learning and memory function, although the effect of CR was significantly greater. Both CR and RSV downregulated p53 and upregulated IGF-1 in hippocampal CA1 region of mice.
  
  
  CONCLUSIONS
  We demonstrate that CR and RSV may improve learning and memory by downregulating p53 and upregulating IGF-1 in hippocampal CA1 region of juvenile mice.
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China; Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China.
authors.forename: Bao-Lei
authors.initials: BL
authors.lastname: Xu
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China; Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Ma
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhao
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.
authors.forename: Jing-Shuang
authors.initials: JS
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
keywords: Caloric restriction; IGF-1; Learning; Resveratrol; memory; p53