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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.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2015 Aug; Vol. 52 (1), pp. 464-77. Date of Electronic Publication: 2014 Sep 09. - Publication Year :
- 2015
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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.
- Subjects :
- Aging pathology
Alzheimer Disease pathology
Animals
Apoptosis drug effects
Bromodeoxyuridine metabolism
Cell Adhesion Molecules, Neuronal metabolism
Cell Line
Dentate Gyrus pathology
Extracellular Matrix Proteins metabolism
Glial Fibrillary Acidic Protein metabolism
Humans
Memantine pharmacology
Mice, Transgenic
Microglia drug effects
Microglia pathology
Nerve Tissue Proteins metabolism
Plaque, Amyloid pathology
Reelin Protein
SOXB1 Transcription Factors metabolism
Serine Endopeptidases metabolism
Alzheimer Disease drug therapy
Amyloid beta-Protein Precursor genetics
Hippocampus pathology
Memantine therapeutic use
Neuroglia pathology
Neuroprotection drug effects
Presenilin-1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 52
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 25195698
- Full Text :
- https://doi.org/10.1007/s12035-014-8875-6