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Protection of Radial Glial-Like Cells in the Hippocampus of APP/PS1 Mice: a Novel Mechanism of Memantine in the Treatment of Alzheimer’s Disease

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Abstract

The failure of adult neurogenesis in the hippocampal dentate gyrus (DG) is closely correlated with memory decline in Alzheimer’s disease (AD). Radial glial-like cells (RGLs) localized to the adult DG generate intermediate progenitor cells and immature neurons and thus contribute to adult hippocampus neurogenesis. Memantine (MEM) has been indicated to dramatically increase hippocampal neurogenesis by promoting the proliferation of RGLs. In this study, we examined the effect of MEM on the capacity for hippocampal cell proliferation and the amount of RGLs in APPswe/PS1∆E9 transgenic (APP/PS1) mice between 9 and 13 months of age. MEM could enhance hippocampal neurogenesis and increase the number of RGLs in the DG subgranular zone (DG-SGZ) of APP/PS1 mice of both ages. Moreover, MEM decreased amyloidogenesis in 13-month-old APP/PS1 mice and protected cultured radial glia cells (RGCs, L2.3 cells) from apoptosis induced by the β amyloid peptide (Aβ). Additionally, MEM inhibited microglial activation in a vertical process in DG-SGZ of APP/PS1 mice and decreased interacting with RGL processes. Reelin is involved in the proliferation of RGLs in the hippocampus, which was typically upregulated in the hippocampus of APP/PS1 mice by MEM and thought to be an active signaling pathway associated with the MEM-induced increase in RGLs. Our data suggest a previously uncharacterized role for MEM in treating AD.

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Acknowledgments

This study was supported by the National Nature Science Foundation of China (No. 31071299, No. 81371197). The authors thank Dr. Hedong Li of Sichuan University for providing L2.3 cell line.

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Authors and Affiliations

  1. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Dayu Sun, Junhua Chen & Haiwei Xu

  2. The Battalion 5 of Cadet Brigade, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Dayu Sun

  3. Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Xiaohang Bao & Jing Huang

  4. Department of Histology and Embryology, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Yulong Cai, Jinghui Zhao, Wei Huang & Xiaotang Fan

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  1. Dayu Sun
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  2. Junhua Chen
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  3. Xiaohang Bao
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  4. Yulong Cai
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  9. Haiwei Xu
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Correspondence to Xiaotang Fan or Haiwei Xu.

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Sun, D., Chen, J., Bao, X. et al. Protection of Radial Glial-Like Cells in the Hippocampus of APP/PS1 Mice: a Novel Mechanism of Memantine in the Treatment of Alzheimer’s Disease. Mol Neurobiol 52, 464–477 (2015). https://doi.org/10.1007/s12035-014-8875-6

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