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. 2015 Nov;18(11):1118-23.

Comparison of the Effects of Resveratrol and Caloric Restriction on Learning and Memory in Juvenile C57BL/6J Mice

Free PMC article

Comparison of the Effects of Resveratrol and Caloric Restriction on Learning and Memory in Juvenile C57BL/6J Mice

Bao-Lei Xu et al. Iran J Basic Med Sci. .
Free PMC article


Objectives: 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.

Conclusion: 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.

Keywords: Caloric restriction; IGF-1; Learning; Resveratrol; memory; p53.


Figure 1
Figure 1
Physiological changes in mice fed caloric restriction (CR) or resveratrol (RSV) diet. Mice were fed normal, CR or RSV diet for 6 months. Animal body weight (A), blood glucose level (B), serum cholesterol, serum triglyceride (TG), serum insulin, or serum IGF-1 levels (C) are shown. *P<0.05, **P<0.01 compared with control; ##P<0.01 compared with CR. N=6 for each group
Figure 2
Figure 2
Learning and memory function of mice as assessed with the Morris water maze test. Escape latency (A) and swimming distance (B) of mice in normal control, CR, and RSV groups are shown. *P<0.05 compared with control; #P<0.05, ##P <0.01 compared with LC. N= 12 for each group
Figure 3
Figure 3
Expression of SIRT1 and insulin signaling pathway regulators. (A) The protein expressions of SIRT1, p53, p16, PPARγ, PI3K, p-CREB, and IGF-1 were assessed using immunohistochemistry. Magnification ×400. (B) The number of immunopositive neurons per area in hippocampal CA1 region is shown. **P<0.01 compared with control; #P<0.05, ##P <0.01 compared with CR. N=6 for each group

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