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Caloric restriction can improve learning ability in C57/BL mice via regulation of the insulin-PI3K/Akt signaling pathway

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Abstract

To identify the molecular mechanism underlying improved spatial learning ability of C57/BL mice on a caloric restricted (CR) diet. Seven-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n = 10), high energy group (n = 10), and low energy group (CR group, n = 10). Body mass and levels of blood glucose were measured every 2 weeks over the course of 30 weeks. After 30 weeks, metabolic parameters, serum total cholesterol, and insulin-like growth factor 1 (IGF-1) were measured, and learning and memory ability of animals were tested using the Morris water maze. The expression of insulin signaling pathway-related proteins in the brain tissues also were tested for molecular mechanism. When compared with the NC group, body weight, and levels of serum glucose decreased in the CR group and increased in the high energy group at all time points tested. Average escape latency and swimming distance were lower in the CR group as compared to the control group after 30 weeks. The serum cholesterol level of the high energy group was significantly higher than that of the control group. The expressions of IGF-1, IR, IRS-1, PI3K, Akt/PKB, and p-CREB protein in the CR group were significantly lower and the expressions of PI3K and Akt/PKB protein in the high energy group were significantly lower than those of the control group at post 30 weeks treatment. Our findings demonstrate that the low energy diet may improve hippocampus-dependent spatial learning ability in C57/BL mice, possibly through a regulatory mechanism of the insulin-PI3K/Akt signaling pathway.

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Acknowledgments

This work was supported by grants from the Beijing Natural Science Foundation (7132044), Capital Health Development Research Fund (2011-1001-02), Ministry of Education in China Project of Humanities and Social Sciences (12YJCZH146), and Beijing Municipal Health Bureau Research Fund (Jing 13-02).

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Authors and Affiliations

  1. Central Laboratory, Xuanwu Hospital of Capital Medical University, Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, #45 Changchun Street, Beijing, 100053, Xicheng District, China

    Lina Ma, Zhiwei Zhao, Rong Wang, Xu Zhang, Jingyan Zhang, Wen Dong, Baolei Xu & Jingshuang Zhang

  2. Department of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China

    Lina Ma

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  1. Lina Ma
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  2. Zhiwei Zhao
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  3. Rong Wang
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  4. Xu Zhang
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  6. Wen Dong
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Correspondence to Rong Wang.

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Ma, L., Zhao, Z., Wang, R. et al. Caloric restriction can improve learning ability in C57/BL mice via regulation of the insulin-PI3K/Akt signaling pathway. Neurol Sci 35, 1381–1386 (2014). https://doi.org/10.1007/s10072-014-1717-5

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  • DOI: https://doi.org/10.1007/s10072-014-1717-5

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