Resveratrol prevents high-calorie diet-induced learning and memory dysfunction in juvenile C57BL/6J mice.

OBJECTIVE: Because resveratrol (RSV) has been shown to improve learning and memory, so we investigated the potential benefit of RSV on learning and memory deficits in juvenile mice fed with a HC diet and explored the molecular mechanisms underlying this process. METHODS: Six-week-old C57BL/6J mice were divided into three different diet groups: control, HC diet, and HC + RSV diet. Serum insulin and insulin-like growth factor 1 (IGF-1) levels were measured using enzyme-linked immunosorbent assays. Protein expression was examined by immunohistochemistry and western blotting. RESULTS: Administration of RSV daily (30 mg/kg) prevented the HC diet-induced increase in juvenile animal body weight but did not improve any other physiological conditions, including fasting blood glucose and serum cholesterol, triglyceride, insulin, and IGF-1 levels. However, RSV did prevent learning and memory deficits in the HC group. Peroxisome proliferator-activated receptor gamma (PPARγ) was downregulated in the CA1 region of the hippocampus in both the HC and HC + RSV groups, but the reduction was significantly greater in the HC + RSV group (P < .01 compared with the HC group). Moreover, although the HC diet reduced the number of p16-positive neurons, the HC + RSV diet significantly upregulated p16 expression in the CA1 region of the hippocampus (P < .01 compared with the HC group). CONCLUSIONS: RSV protected against learning and memory impairments in juvenile animals fed with a HC diet, possibly via upregulation of p16 or downregulation of PPARγ in the hippocampal CA1 region.

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

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.

Effects of Caloric Intake on Learning and Memory Function in Juvenile C57BL/6J Mice.

Dietary composition may influence neuronal function as well as processes underlying synaptic plasticity. In this study, we aimed to determine the effect of high and low caloric diets on a mouse model of learning and memory and to explore mechanisms underlying this process. Mice were divided into three different dietary groups: normal control (n = 12), high-caloric (HC) diet (n = 12), and low-caloric (LC) diet (n = 12). After 6 months, mice were evaluated on the Morris water maze to assess spatial memory ability. We found that HC diet impaired learning and memory function relative to both control and LC diet. The levels of SIRT1 as well as its downstream effectors p53, p16, and peroxisome proliferator-activated receptor γ (PPARγ) were decreased in brain tissues obtained from HC mice. LC upregulated SIRT1 but downregulated p53, p16, and PPARγ. The expressions of PI3K and Akt were not altered after HC or LC diet treatment, but both LC and HC elevated the levels of phosphorylated-cAMP response element-binding protein (p-CREB) and IGF-1 in hippocampal CA1 region. Therefore, HC diet-induced dysfunction in learning and memory may be prevented by caloric restriction via regulation of the SIRT1-p53 or IGF-1 signaling pathways and phosphorylation of CREB.

Autophagy involving age-related cognitive behavior and hippocampus injury is modulated by different caloric intake in mice.

Recent studies indicated that different caloric intake may influence neuronal function. Excessive caloric intake associated with accelerated aging of the brain and increased the risk of neurodegenerative disorders. And low caloric intake (caloric restriction, CR) could delay aging, and protect the central nervous system from neurodegenerative disorders. The underlying mechanisms remain poorly understood. In this study, thirty six-week-old male C57/BL male mice were randomly divided into three different dietary groups: normal control (NC) group (fed standard diet), CR group (fed low-caloric diet) and high-calorie (HC) group (fed high-caloric diet). After 10 months, spatial memory ability was determined by Morris water maze. Pathological changes of the hippocampus cells were detected with HE and Nissl staining. The expression of proteins involved in autophagy in the hippocampus was determined by immunofluorescence and Western blot. The result of Morris water maze showed that the learning and memory capacity significantly increased in the CR group, and significantly decreased in the HC group. HE and Nissl staining showed cells damaged obviously in the HC group. The expression of mTOR and p62 was increased in the HC group, and decreased in the CR group. The expression of Beclin1, LC3 and cathepsin B was decreased in the HC group, and increased in the CR group. Our findings demonstrate that long-term high caloric intake is a risk factor that can significantly contribute to the development of neurological disease via suppressing autophagy, and CR may prevent age-related learning ability impairment via activating autophagy in mice.

Comparison of the effects of resveratrol and caloric restriction on learning and memory in juvenile C57BL/6J mice.

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.