期刊
MOLECULAR NEUROBIOLOGY
卷 52, 期 1, 页码 464-477出版社
HUMANA PRESS INC
DOI: 10.1007/s12035-014-8875-6
关键词
Alzheimer's disease; Hippocampus; Neurogenesis; Memantine; Reelin
资金
- National Nature Science Foundation of China [31071299, 81371197]
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/PS1a dagger 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 beta amyloid peptide (A beta). 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据