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Chronic adjunction of 1-deoxynojirimycin protects from age-related behavioral and biochemical changes in the SAMP8 mice

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Abstract

Several studies have indicated that a caloric restriction mimetic or treatment for type 2 diabetes may reverse brain aging. Therefore, we investigated the effect of 1-deoxynojirimycin (DNJ), an alkaloid acting as an inhibitor of α-glucosidase, on age-related behavioral and biochemical changes. SAMP8 mice were randomly assigned to a control group labeled “old” or to the 10- or 20-mg/kg/day DNJ groups. The mice in the DNJ groups were administered DNJ orally from 3 to 9 months of age, and then, a “young” control group was added to analyze the age effect. The old controls exhibited significant declines in sensorimotor ability, open-field anxiety, spatial and nonspatial memory abilities, and age-related biochemical changes, including decreased serum insulin level; increased levels of insulin-like growth factor 1 receptor, presynaptic protein synaptotagmin-1, and astrocyte activation; and decreased levels of insulin receptor, brain-derived neurotrophic factor, presynaptic protein syntaxin-1, and acetylation of histones H4 at lysine 8 in the dorsal hippocampus. Significant correlations exist between the age-related behavioral deficits and the serological and histochemical data. Chronic DNJ treatment alleviated these age-related changes, and the 20-mg/kg/day DNJ group showed more significant improvement. Thus, DNJ may have the potential to maintain successful brain aging.

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Acknowledgments

This work was financially supported by the National Foundation of Nature Science of China (81370444), the Natural Science Foundation for the Youth of China (81301094), the Special Fund for Agro-scientific Research in the Public Interest of China (No. 201403064), and the key project of the Natural Science from the Education Department of Anhui Province (ZD2008007-1 and 2).

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    1. Department of Neurology, the Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Hefei, 238000, People’s Republic of China

      Gui-Hai Chen

    2. School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, 230009, Anhui, People’s Republic of China

      Gui-Hai Chen, Xue-Qin Hu & Zhao-Jun Wei

    3. Department of Rheumatism and Immunity, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China

      Jing-Jing Tong

    4. Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China

      Gui-Hai Chen, Jing-Jing Tong, Fang Wang, Xue-Wei Li & Fei Tao

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    Gui-Hai Chen and Jing-Jing Tong contributed equally to this work.

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    Chen, GH., Tong, JJ., Wang, F. et al. Chronic adjunction of 1-deoxynojirimycin protects from age-related behavioral and biochemical changes in the SAMP8 mice. AGE 37, 102 (2015). https://doi.org/10.1007/s11357-015-9839-0

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    • DOI: https://doi.org/10.1007/s11357-015-9839-0

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