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

ABSTRACT

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.

KEYWORDS:

• RSV
• HC diet
• learning
• memory
• p16

Acknowledgments

This study was supported by the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201706) as well as the National Key R&D Program of China (Grant No. 2016YFC1306300).

Disclosure statement

We declare that we have no conflicts of interest.

Additional information

Funding

This work was supported by the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201706] as well as the National Key Research and Development Program of China [2016YFC1306300].

Notes on contributors

Rong Wang

Rong Wang is a Researcher, Professor, PhD candidate, neurobiology of capital medical university, Director of the center laboratoary of xuanwu hospital.